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Osaka, Japan

Osaka University , or Handai , is a national university located in Osaka, Japan. It is the sixth oldest university in Japan as the Osaka Prefectural Medical College, and one of Japan's National Seven Universities. Numerous prominent scientists have worked at Osaka University such as the Nobel Laureate in Physics Hideki Yukawa. Wikipedia.

Einaga M.,Osaka University
Nature Physics | Year: 2016

A superconducting critical temperature above 200 K has recently been discovered in H2S (or D2S) under high hydrostatic pressure. These measurements were interpreted in terms of a decomposition of these materials into elemental sulfur and a hydrogen-rich hydride that is responsible for the superconductivity, although direct experimental evidence for this mechanism has so far been lacking. Here we report the crystal structure of the superconducting phase of hydrogen sulfide (and deuterium sulfide) in the normal and superconducting states obtained by means of synchrotron X-ray diffraction measurements, combined with electrical resistance measurements at both room and low temperatures. We find that the superconducting phase is mostly in good agreement with the theoretically predicted body-centred cubic (bcc) structure for H3S. The presence of elemental sulfur is also manifest in the X-ray diffraction patterns, thus proving the decomposition mechanism of H2S to H3S + S under pressure. © 2016 Nature Publishing Group Source

Sherwood R.,Sloan Kettering Cancer Center | Takahashi T.S.,Osaka University | Jallepalli P.V.,Sloan Kettering Cancer Center
Genes and Development | Year: 2010

The ring-shaped cohesin complex links sister chromatids and plays crucial roles in homologous recombination and mitotic chromosome segregation. In cycling cells, cohesin's ability to generate cohesive linkages is restricted to S phase and depends on loading and establishment factors that are intimately connected to DNA replication. Here we review how cohesin is regulated by the replication machinery, as well as recent evidence that cohesin itself influences how chromosomes are replicated. © 2010 by Cold Spring Harbor Laboratory Press. Source

Takehara T.,Osaka University
Expert Review of Anti-Infective Therapy | Year: 2014

Simeprevir is a second-wave hepatitis C virus NS3/4A protease inhibitor that was designed to optimize its antiviral activity, safety, drug-drug interactions, and pharmacokinetic profile. When used to treat patients with hepatitis C virus genotype 1, simeprevir is coadministered with peginterferon and ribavirin for 12 weeks, followed by double therapy with Peg-IFN and ribavirin for an additional 12 or 36 weeks. Phase III studies achieved a sustained virologic response in 80-90% of treatment-naïve patients (International Phase III studies QUEST-1/2: 80/81%; Japanese Phase III trial CONCERTO-1: 89%). Unlike with the first protease inhibitors, telaprevir or boceprevir, used in triple therapy, when using simeprevir the frequency of clinically problematic adverse events such as anemia, rash, and digestive symptoms is almost comparable to that of double therapy. The advent of simeprevir has enabled interferon therapy, which started as monotherapy in early 1990s, to reach its maximum efficacy and arrive at what can be considered its final form at least in genotype 1b. © Informa UK, Ltd. Source

Yagi T.,Osaka University
Journal of Neurogenetics | Year: 2013

The mammalian brain is a complex multicellular system involving enormous numbers of neurons. The neuron is the basic functional unit of the brain, and neurons are organized by specialized intercellular connections into circuits with many other neurons. Physiological studies have revealed that individual neurons have remarkably selective response properties, and this individuality is a fundamental requirement for building complex and functionally diverse neural networks. Recent molecular biological studies have revealed genetic bases for neuronal individuality in the mammalian brain. For example, in the rodent olfactory epithelium, individual olfactory neurons express only one type of odorant receptor (OR) out of the over 1000 ORs encoded in the genome. The expressed OR determines the neuron's selective chemosensory response and specifies its axonal targeting to a particular olfactory glomerulus in the olfactory bulb. Neuronal diversity can also be generated in individual cells by the independent and stochastic expression of autosomal alleles, which leads to functional heterozygosity among neurons. Among the many genes that show autosomal stochastic monoallelic expression, approximately 50 members of the clustered protocadherins (Pcdhs) are stochastically expressed in individual neurons in distinct combinations. The clustered Pcdhs belong to a large subfamily of the cadherin superfamily of homophilic cell-adhesion proteins. Loss-of-function analyses show that the clustered Pcdhs have critical functions in the accuracy of axonal projections, synaptic formation, dendritic arborization, and neuronal survival. In addition, cis-tetramers, composed of heteromultimeric clustered Pcdh members, represent selective binding units for cell-cell interactions, and provide exponential numbers of possible cell-surface relationships between individual neurons. The extensive molecular diversity of neuronal cell-surface proteins affects neurons' individual properties and connectivities. The molecular features of the diverse clustered Pcdh molecules suggest that they provide a genetic basis for neuronal individuality and appropriate neuronal wiring in the brain. © 2013 Informa Healthcare USA, Inc. Source

OBJECTIVES:: To noninvasively investigate regional differences in tear film stability and meibomian glands in patients with aqueous-deficient dry eye. METHODS:: Forty-nine dry eyes and 31 normal eyes were analyzed. A corneal topographer with a tear film scanning function was used for noninvasive tear film break-up time (NI-TFBUT) measurements and meibomian gland observations. The NI-TFBUT values and location of the first tear film break-up point were recorded in four quadrants. Meibomian gland loss was graded for each eyelid using meiboscores. Lid margin abnormality was scored from zero to four according to the number of existing abnormalities. The NI-TFBUT values and meiboscores were compared between two groups, and regional differences in NI-TFBUT values and meiboscores were analyzed. Also, the correlation between the NI-TFBUT and ocular surface examination results were investigated. RESULTS:: The NI-TFBUT values and meiboscores were significantly lower and higher, respectively, for the dry eye group than for the normal group. In the dry eye group, the occurrence rate for first tear film break-up was the highest in the inferior nasal quadrant, and the mean meiboscore was significantly higher for the upper eyelids than for the lower eyelids. The NI-TFBUT and lid margin abnormality scores showed a weak negative correlation, and the NI-TFBUT values and meiboscores showed no correlation. CONCLUSIONS:: Compared to normal eyes, aqueous-deficient dry eyes show significant regional differences in tear film stability and meibomian glands. Considering these regional differences, the overall observation of the ocular surface, including both upper and lower eyelids, will aid clinicians in understanding this condition better. © 2015 Contact Lens Association of Ophthalmologists, Inc. Source

Nishinaka T.,Osaka University
Journal of High Energy Physics | Year: 2011

We study the wall-crossing phenomena of D4-D2-D0 bound states with two units of D4-brane charge on the resolved conifold. We identify the walls of marginal stability and evaluate the discrete changes of the BPS indices by using the Kontsevich-Soibelman wall-crossing formula. In particular, we find that the field theories on D4-branes in two large radius limits are properly connected by the wall-crossings involving the flop transition of the conifold. We also find that in one of the large radius limits there are stable bound states of two D4-D2-D0 fragments. © SISSA 2011. Source

Haba N.,Osaka University | Seto O.,Hokkai Gakuen University
Progress of Theoretical Physics | Year: 2011

It is well-known that leptogenesis in low energy scale is difficult in the conventional Type-I seesaw mechanism with hierarchical right-handed neutrino masses. We show that in a class of two Higgs doublet model, where one Higgs doublet generates masses of quarks and charged leptons whereas the other Higgs doublet with a tiny vacuum expectation value generates neutrino Dirac masses, large Yukawa couplings lead to a large enough CP asymmetry of the right-handed neutrino decay. Thermal leptogenesis suitably works at the low energy scale as keeping no enhancement of lepton number violating wash-out effects. We will also point out that thermal leptogenesis works well without confronting the gravitino problem in a supersymmetric neutrinophilic Higgs doublet model with gravity mediated supersymmetry breaking. Neutralino dark matter and baryon asymmetry generation by thermal leptogenesis are easily compatible in our setup. Source

Morita S.,Osaka University
Journal of Electron Microscopy | Year: 2011

Scanning tunneling microscopy (STM) has opened up the new nanoworlds of scanning probe microscopy. STM is the first-generation atomic tool that can image, evaluate and manipulate individual atoms and consequently can create nanostructures by true bottom-up methods based on atom-by-atom manipulation. Atomic force microscopy is a second-generation atomic tool that has followed the footsteps of STM, and which is now opening doors to a new atom world based on using nanoscale forces. © The Author 2011. Published by Oxford University Press [on behalf of Japanese Society of Microscopy]. All rights reserved. Source

Nishida H.,Osaka University
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2012

Muscle formation in ascidian embryos has been investigated for more than a century as a representative example of cell fate specification by localized maternal factors within the egg cytoplasm. Observations of colored cytoplasm in combination with micromanipulation techniques have suggested the presence of a muscle-forming factor. The molecular basis has been elucidated with the discovery of macho-1. macho-1 mRNA is already present in the unfertilized egg, and translocates to the posterior region of the egg during ooplasmic movements. It encodes a zinc-finger transcription factor that positively regulates the expression of target genes. macho-1-binding cis-elements have been identified in muscle-specific zygotic genes. Maternally localized macho-1 appears to have originated in the ascidian lineage, but it activates a muscle-forming developmental program that is shared by the vertebrates. macho-1 is also involved in establishment of the anterior-posterior axis as a competence factor in mesenchyme induction in the posterior region. It is suggested that translation of the macho-1 protein is initiated at the eight-cell stage, and that the protein is inherited by all descendant blastomeres of the posterior-vegetal region. The macho-1 activities in nonmuscle descendants are suppressed or modified by cell interactions during the cleavage stages. In addition to the primary muscle specified by maternal macho-1, ascidian embryos develop secondary muscle, whose fate is determined by cell interactions. Dozens of maternal mRNAs show similar localization to macho-1, and these are known as postplasmic/PEM RNAs, being also involved in various posterior-specific developmental events. Evolutionary aspects relevant to macho-1 and tail muscle formation are also discussed in this article. © 2011 Wiley Periodicals, Inc. Source

Fukuda I.,RIKEN | Nakamura H.,Osaka University
Biophysical Reviews | Year: 2012

Several non-Ewald methods for calculating electrostatic interactions have recently been developed, such as the Wolf method, the reaction field method, the pre-averaging method, and the zero-dipole summation method, for molecular dynamics simulations of various physical systems, including biomolecular systems. We review the theories of these approaches and their potential applications to molecular simulations, and discuss their relationships. © 2012 The Author(s). Source

Hirasawa T.,Osaka University
Sub-cellular biochemistry | Year: 2012

Glutamate is a commercially important chemical. It is used as a flavor enhancer and is a major raw material for producing industrially useful chemicals. A coryneform bacterium, Corynebacterium glutamicum, was isolated in 1956 by Japanese researchers as a glutamate-overproducing bacterium and since then, remarkable progress in glutamate production has been made using this microorganism. Currently, the global market for glutamate is over 2.5 million tons per year. Glutamate overproduction by C. glutamicum is induced by specific treatments-biotin limitation, addition of fatty acid ester surfactants such as Tween 40, and addition of β-lactam antibiotics such as penicillin. Molecular biology and metabolic engineering studies on glutamate overproduction have revealed that metabolic flow is significantly altered by these treatments. These studies have also provided insight into the molecular mechanisms underlying these changes. In this chapter, we review our current understanding of the molecular mechanisms of glutamate overproduction in C. glutamicum, and we discuss the advances made by metabolic engineering of this microorganism. Source

Xia J.,Wuhan University | Chen L.,Wuhan University | Yanagida S.,Osaka University
Journal of Materials Chemistry | Year: 2011

Conductive polymers have been widely applied as counter electrodes in dye-sensitized solar cells. However, as one of many materials in the conductive polymer family, polypyrrole attracts little attention in this field. In this paper, polypyrrole (PPy) was synthesized by vapour phase polymerization (VPP) and electropolymerization (EP) and these PPys were employed as counter electrodes in dye-sensitized solar cells. Comparing this to the regularly used Pt counter electrode, both of them show good catalytic behaviour in dye-sensitized solar cells though the PPy electrodes have a slightly lower fill factor. Such investigation will broaden the application of conductive polymers in DSCs. Our study indicates that polypyrrole is a good candidate to replace the Pt counter electrode in DSCs. Taking into consideration the regular solvent used in DSCs, it is recommended that an insoluble conductive polymer is a good choice for the counter electrode in DSCs. © 2011 The Royal Society of Chemistry. Source

Patil A.,Tokyo Medical University | Nakai K.,Tokyo Medical University | Nakamura H.,Osaka University
Nucleic Acids Research | Year: 2011

Despite the availability of a large number of protein- protein interactions (PPIs) in several species, researchers are often limited to using very small subsets in a few organisms due to the high prevalence of spurious interactions. In spite of the importance of quality assessment of experimentally determined PPIs, a surprisingly small number of databases provide interactions with scores and confidence levels. We introduce HitPredict (http:// hintdb.hgc.jp/htp/), a database with qualityassessed PPIs in nine species. HitPredict assigns a confidence level to interactions based on a reliability score that is computed using evidence from sequence, structure and functional annotations of the interacting proteins. HitPredict was first released in 2005 and is updated annually. The current release contains 36 930 proteins with 176 983 non-redundant, physical interactions, of which 116 198 (66%) are predicted to be of high confidence. © The Author(s) 2010. Source

Nagatsuma T.,Osaka University
IEEE Photonics Journal | Year: 2014

There has been an increasing interest in the application of terahertz (THz) waves to broadband wireless communications. In particular, use of frequencies above 275 GHz is one of the big concerns among radio scientists and engineers, because these frequency bands have not yet been allocated at specific active services, and there is a possibility to employ extremely large bandwidths for ultrabroadband wireless communications. Introduction of photonics technologies for signal generation, modulation, and detection is effective not only to enhance the bandwidth and/or the data rate but also to combine fiber-optic and wireless networks. This paper reviews recent progress in THz wireless communications using telecom-based photonics technologies towards 100 Gb/s. © 2009-2012 IEEE. Source

A pancreatic fistula is a serious postoperative complication that can occur after gastrectomy with lymphadenectomy for gastric cancer. The aim of this prospective study was to analyze the usefulness of the local application of fibrin glue sealant (FG) and polyglycolic acid sheets (PAS) in preventing pancreatic fistula formation after gastrectomy. The surface of the pancreas was covered with FG and PAS after peri-pancreatic lymph node dissection in 34 patients (F/P group). The postoperative outcome was compared with historical control subjects who did not receive the same application (control group, 64 patients). A pancreatic fistula occurred in three patients in the control group but in none the F/P group (P = 0.049). The volume of drainage fluid on postoperative day (POD) 1 and 3 was smaller in the F/P group than in the control group (POD1: F/P group, 80 ml; control: 150 ml, P < 0.001; POD3: 60 vs. 120 ml, P < 0.001). The amylase levels in the drainage fluid on POD1 and 3 were also significantly lower in the F/P group than in the control group (POD1: F/P group, 660 U/L; control: 1220 U/L, P = 0.030; POD2: 270 vs. 830 U/L, P = 0.038; POD3, 160 vs. 630 U/L, P = 0.041). The application of FG and PAS after LAG helps to prevent pancreatic fistula formation. Source

Sugiyama H.,Osaka University
Japanese Journal of Clinical Oncology | Year: 2010

Wilms' tumor gene WT1 encodes a transcription factor and plays an important role in cell growth and differentiation. The WT1 gene is highly expressed in leukemia and various types of solid tumors, whereas WT1 is a tumor marker convenient for the detection of minimal residual disease of leukemia. The WT1 gene was originally defined as a tumor suppressor gene, but we proposed that it was, on the contrary, an oncogene. Furthermore, the WT1 protein has proven to be a promising tumor-associated antigen, in which many human leukocyte antigen class I-or II-restricted WT1 epitopes have been identified. Clinical trials of WT1-targeted immunotherapy have confirmed its safety and clinical efficacy. WT1-specific cytotoxic T lymphocytes and WT1 antibodies are spontaneously induced in tumor-bearing patients, probably because of high immunogenicity of the WT1 protein. WT1-specific cytotoxic T lymphocytes make a major contribution to the graft-versus-leukemia effect after allogenic stem cell transplantation. When 75 cancer antigens including WT1 were prioritized according to several criteria such as therapeutic function and immunogenicity, WT1 was ranked as the top antigen. These findings suggest that a new era of WT1 immunotherapy is imminent. © The Author (2010). Published by Oxford University Press. All rights reserved. Source

Shiraishi Y.,Research Center for Solar Energy Chemistry | Sakamoto H.,Research Center for Solar Energy Chemistry | Sugano Y.,Research Center for Solar Energy Chemistry | Ichikawa S.,Osaka University | Hirai T.,Research Center for Solar Energy Chemistry
ACS Nano | Year: 2013

Visible light irradiation (λ > 450 nm) of Pt-Cu bimetallic alloy nanoparticles (∼3-5 nm) supported on anatase TiO2 efficiently promotes aerobic oxidation. This is facilicated via the interband excitation of Pt atoms by visible light followed by the transfer of activated electrons to the anatase conduction band. The positive charges formed on the nanoparticles oxidize substrates, and the conduction band electrons reduce molecular oxygen, promoting photocatalytic cycles. The apparent quantum yield for the reaction on the Pt-Cu alloy catalyst is ∼17% under irradiation of 550 nm monochromatic light, which is much higher than that obtained on the monometallic Pt catalyst (∼7%). Cu alloying with Pt decreases the work function of nanoparticles and decreases the height of the Schottky barrier created at the nanoparticle/anatase heterojunction. This promotes efficient electron transfer from the photoactivated nanoparticles to anatase, resulting in enhanced photocatalytic activity. The Pt-Cu alloy catalyst is successfully activated by sunlight and enables efficient and selective aerobic oxidation of alcohols at ambient temperature. © 2013 American Chemical Society. Source

Gao X.,Guangdong University of Technology | You D.,Guangdong University of Technology | Katayama S.,Osaka University
IEEE Transactions on Industrial Electronics | Year: 2012

This paper proposes a method of seam tracking monitoring during high-power fiber laser welding. A visual sensor system was employed to capture the infrared images of molten pools and the surroundings in the laser welding process. A weld seam position variable was extracted by the image difference and centroid algorithms. The state and measurement equations for weld seam position were established based on an eigenvector derived from the weld seam position variable. A Sage-Husa adaptive Kalman filter (AKF), as an estimator of the noise statistical characteristics, was applied in order to enhance the filtering precision. By embedding an Elman neural network into the AKF, an error estimator was used to compensate for the filtering errors. The results of the welding experiments have demonstrated the effectiveness of the proposed method to improve the accuracy of weld detection. © 2012 IEEE. Source

Wang Y.,University of Michigan | Kim E.,University of Michigan | Wang X.,University of Michigan | Novitch B.G.,University of California at Los Angeles | And 3 more authors.
Cell | Year: 2012

Germline mutations in the RAS/ERK signaling pathway underlie several related developmental disorders collectively termed neuro-cardio-facial- cutaneous (NCFC) syndromes. NCFC patients manifest varying degrees of cognitive impairment, but the developmental basis of their brain abnormalities remains largely unknown. Neurofibromatosis type 1 (NF1), an NCFC syndrome, is caused by loss-of-function heterozygous mutations in the NF1 gene, which encodes neurofibromin, a RAS GTPase-activating protein. Here, we show that biallelic Nf1 inactivation promotes Erk-dependent, ectopic Olig2 expression specifically in transit-amplifying progenitors, leading to increased gliogenesis at the expense of neurogenesis in neonatal and adult subventricular zone (SVZ). Nf1-deficient brains exhibit enlarged corpus callosum, a structural defect linked to severe learning deficits in NF1 patients. Strikingly, these NF1-associated developmental defects are rescued by transient treatment with an MEK/ERK inhibitor during neonatal stages. This study reveals a critical role for Nf1 in maintaining postnatal SVZ-derived neurogenesis and identifies a potential therapeutic window for treating NF1-associated brain abnormalities. © 2012 Elsevier Inc. Source

Takai S.,Osaka University | Kumar R.,Iowa State University
IEEE Transactions on Automatic Control | Year: 2012

The task of failure prognosis requires the prediction of impending failures. This technical note formulates and studies the problem of distributed prognosis of discrete event systems, where the local prognosers exchange their observations for the sake of arriving at a prognostic decision. The observations are exchanged over communication channels that introduce bounded delays. A property of joint-prognosability is introduced to capture the condition under which any failure can be predicted by some local prognoser prior to its occurrence. We provide an algorithm to check the joint-prognosability property. © 2012 IEEE. Source

Takaya Y.,Osaka University
International Journal of Automation Technology | Year: 2013

In-process and on-machine measurements are used to evaluate a variety of machining factors and conditions as well as the work done on the machine tool. With the increasing complexity of machining processes and greater requirements for accuracy and precision, the demand for advanced methods for process optimization has also increased. To meet this demand, process quality management (QM) requires an expansion of manufacturing metrology to include comprehensive closed-loop control of the machining process. To eliminate the effects of disturbances on the machining process and adjust the control quantities to optimal values for robustness, in-process and on-machine measurements are very essential. In this paper, we review technical trends in in-process and on-machine measurements for process QM and conventional quality control (QC) of products. Spreading measurement targets and applications are comprehensively reviewed. Source

Fukuzumi S.,Osaka University | Fukuzumi S.,Ewha Womans University | Karlin K.D.,Ewha Womans University | Karlin K.D.,Johns Hopkins University
Coordination Chemistry Reviews | Year: 2013

The kinetics and thermodynamics of formation of Cu(II)-superoxo (Cu-O 2) complexes by the reaction of Cu(I) complexes with dioxygen (O 2) and the reduction of Cu(II)-superoxo complexes to dinuclear Cu-peroxo complexes are discussed. In the former case, electron transfer from a Cu(I) complex to O 2 occurs concomitantly with binding of O 2 -to the corresponding Cu(II) species. This is defined as an inner-sphere Cu(II) ion-coupled electron transfer process. Electron transfer from another Cu(I) complex to preformed Cu(II)-superoxo complexes also occurs concomitantly with binding of the Cu(II)-peroxo species with the Cu(II) species to produce the dinuclear Cu-peroxo (Cu 2-O 2) complexes. The kinetics and thermodynamics of outer-sphere electron-transfer reduction of Cu 2-O 2 complexes are also been discussed in light of the Marcus theory of outer-sphere electron transfer. © 2012 Elsevier B.V.. Source

Kataoka I.,Osaka University
Journal of Nuclear Science and Technology | Year: 2013

The Tohoku Region Pacific Coast Earthquake and subsequent severe accident (SA) in Fukushima Daiichi Nuclear Power Station caused unprecedented disaster in Japan. Before this accident, considerable researches on SAs had been carried out in Japan. However, unfortunately, such researches could not prevent the accident due to the unexpected huge Tsunami. However, the researches on SAs become more and more important in order to make clear the causes of the accident in Fukushima and improve the safety of nuclear power plants in Japan. In view of this, review on researches on thermal hydraulics in SAs in light water reactors was carried out. Important thermal-hydraulic phenomena in SAs were identified. Research activities on each phenomenon were surveyed mainly based on the articles published in Journal of Nuclear Science and Technology of Atomic Energy Society of Japan. © 2013 Atomic Energy Society of Japan. Source

Kawata S.,Osaka University
Japanese Journal of Applied Physics | Year: 2013

Plasma resonance in metals exhibits some unique optical phenomena that occur on the surface of metal with nanostructures. The use of surface plasmons has been proposed in various fields, such as nanometer-resolution near-field optical microscopy, nanoscale optical circuits, singlemolecule detection, molecular sensors, cancer treatment, solar cells, lasers, and holography. The study of plasma resonance is called "plasmonics" and is expected as a new field of nanophotonics. In this report, I review the principles and limits of plasmonics and give a future outlook. © 2013 The Japan Society of Applied Physics. Source

Murai T.,Osaka University
Biological Chemistry | Year: 2014

The accumulation of cholesterol is a general feature of cancer tissue, and recent evidence suggests that cholesterol plays critical roles in the progression of cancers, including breast, prostate, and colorectal cancers. The dysregulation of metabolic pathways, including those involved in cholesterol biosynthesis, is implicated in tumor development and cancer progression. Lipid rafts are highly dynamic cholesterol-enriched domains of the cell membrane, involved in various cellular functions, including the regulation of transmembrane signaling at the cell surface. It was recently demonstrated that lipid rafts also play critical roles in cancer cell adhesion and migration. This review focuses on our current understanding of how cholesterol regulation, lipid rafts, and dysregulated cholesterol biosynthesis contribute to cancer development and progression, and the therapeutic potential of cholesterol lowering for cancer prevention and treatment. © 2014 by De Gruyter 2014. Source

Kawamura H.,Osaka University
Journal of Physics: Conference Series | Year: 2011

We discuss the recent experimental data on various frustrated quasi-two-dimensional Heisenberg antiferromagnets from the viewpoint of the Z2-vortex order, which include S=3/2 triangular-lattice antiferromagnet NaCrO2, S=1 triangular-lattice antiferromagnet NiGa2S4, S=1/2 organic triangular-lattice antiferromagnets k-(BEDT-TTF)2Cu2(CN)3 and EtMe 3Sb[Pd(dmit)2]2, and S=1/2 kagome-lattice antiferromagnet volborthite Cu3V2O7(OH) 2-2H2O, etc. © 2011 Published under licence by IOP Publishing Ltd. Source

Shimizu S.,Osaka University
Neurocomputing | Year: 2012

A linear non-Gaussian structural equation model called LiNGAM is an identifiable model for exploratory causal analysis. Previous methods estimate a causal ordering of variables and their connection strengths based on a single dataset. However, in many application domains, data are obtained under different conditions, that is, multiple datasets are obtained rather than a single dataset. In this paper, we present a new method to jointly estimate multiple LiNGAMs under the assumption that the models share a causal ordering but may have different connection strengths and differently distributed variables. In simulations, the new method estimates the models more accurately than estimating them separately. © 2011 Elsevier B.V. Source

Nishikawa H.,Osaka University
Nature Medicine | Year: 2016

CD4+ T cells that express the forkhead box P3 (FOXP3) transcription factor function as regulatory T (Treg) cells and hinder effective immune responses against cancer cells. Abundant Treg cell infiltration into tumors is associated with poor clinical outcomes in various types of cancers. However, the role of Treg cells is controversial in colorectal cancers (CRCs), in which FOXP3+ T cell infiltration indicated better prognosis in some studies. Here we show that CRCs, which are commonly infiltrated by suppression-competent FOXP3hi Treg cells, can be classified into two types by the degree of additional infiltration of FOXP3lo nonsuppressive T cells. The latter, which are distinguished from FOXP3+ Treg cells by non-expression of the naive T cell marker CD45RA and instability of FOXP3, secreted inflammatory cytokines. Indeed, CRCs with abundant infiltration of FOXP3lo T cells showed significantly better prognosis than those with predominantly FOXP3hi Treg cell infiltration. Development of such inflammatory FOXP3lo non-Treg cells may depend on secretion of interleukin (IL)-12 and transforming growth factor (TGF)-β by tissues and their presence was correlated with tumor invasion by intestinal bacteria, especially Fusobacterium nucleatum. Thus, functionally distinct subpopulations of tumor-infiltrating FOXP3+ T cells contribute in opposing ways to determining CRC prognosis. Depletion of FOXP3hi Treg cells from tumor tissues, which would augment antitumor immunity, could thus be used as an effective treatment strategy for CRCs and other cancers, whereas strategies that locally increase the population of FOXP3lo non-Treg cells could be used to suppress or prevent tumor formation. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source

Olsen I.,University of Oslo | Amano A.,Osaka University
Journal of Oral Microbiology | Year: 2015

Outer membrane vesicles (OMVs) from Gram-negative bacteria were first considered as artifacts and were followed with disbelief and bad reputation. Later, their existence was accepted and they became characterized as bacterial bombs, virulence bullets, and even decoys. Today, we know that OMVs also can be involved in cell-cell signaling/communication and be mediators of immune regulation and cause disease protection. Furthermore, OMVs represent a distinct bacterial secretion pathway selecting and protecting their cargo, and they can even be good Samaritans providing nutrients to the gut microbiota maintaining commensal homeostasis beneficial to the host. The versatility in functions of these nanostructures is remarkable and includes both defense and offense. The broad spectrum of usability does not stop with that, as it now seems that OMVs can be used as vaccines and adjuvants or vehicles engineered for drug treatment of emerging and new diseases not only caused by bacteria but also by virus. They may even represent new ways of selective drug treatment. © 2015 Ingar Olsen and Atsuo Amano. Source

Inui S.,Osaka University
Clinical, Cosmetic and Investigational Dermatology | Year: 2015

Uremic pruritus has a great negative influence on quality of life in hemodialysis (HD) patients and, importantly, negatively affects mortality risk. Recently, nalfurafine hydrochloride, an opioid κ-selective agonist, has been officially approved for resistant pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. From clinical observation, it has been suggested that the upper neuron system plays a role in its pathogenesis. According to previous experimental results, using mice injected with opioids, dynorphin suppresses itch through binding κ-opioid receptors, suggesting that κ-opioid opioid receptor agonists act as potential therapeutic reagents for pruritus in HD patients. In Japan, a large-scale placebo-controlled study was performed to examine the efficacy and safety of oral nalfurafine hydrochloride for intractable pruritus in 337 HD patients. Two daily doses of 2.5 or 5 μg nalfurafine or placebo were orally administered for 2 weeks, and clinical responses were analyzed. The results showed that the mean decrease in the visual analog scale for pruritus from baseline was 22 mm in the 5 μg nalfurafine hydrochloride group (n=114) and 23 mm in the 2.5 μg group (n=112). These reductions were statistically significant compared with 13 mm, which is the mean decrease of visual analog scale in the placebo group (n=111), demonstrating that nalfurafine is an effective and safe drug for uremic pruritus in HD patients. Moreover, another open-label trial (n=145) examining the long-term effect of 5 μg oral nalfurafine revealed the maintenance of the antipruritic effect of nalfurafine for 52 weeks. In addition, on the basis of recent data showing κ-opioid receptor expression in the epidermis of atopic dermatitis and psoriasis, nalfurafine hydrochloride also can be potentially used for these two skin diseases. © 2015 Inui. Source

Tanaka S.J.,Aoyama Gakuin University | Takahara F.,Osaka University
Monthly Notices of the Royal Astronomical Society | Year: 2013

Among dozens of young pulsar wind nebulae (PWNe), some have been detected in TeV γ -rays (TeV PWNe), while others have not (non-TeV PWNe). The TeV emission detectability is not correlated with either the spin-down power or the characteristic age of the central pulsars and it is an open question as to what determines the detectability. To study this problem, we investigate the spectral evolution of five young non-TeV PWNe: 3C 58, G310.6-1.6, G292.0+1.8, G11.2-0.3 and SNR B0540-69.3. We use a spectral evolution model that was developed in our previous works to be applied to young TeV PWNe. The TeV γ -ray flux upper limits of non-TeV PWNe give upper or lower limits on parameters such as the age of the PWN and the fraction of spin-down power going into magnetic energy injection (the fraction parameter). Combined with other independent observational and theoretical studies, we can guess a plausible value of the parameters for each object. For 3C 58, we prefer parameters with an age of 2.5 kyr and fraction parameter of 3.0 × 10-3, although the spectral modelling alone does not rule out a lower age and a higher fraction parameter. The fraction parameter of 3.0 × 10-3 is also consistent for other non-TeV PWNe and thus the value is regarded as common to young PWNe, including TeVPWNe. Moreover, we find that the intrinsic properties of the central pulsars are similar: 1048-50 erg for the initial rotational energy and 1042-44 erg for the magnetic energy (2 × 1012-3 × 1013 G for the dipole magnetic field strength at the surface). The TeV detectability is correlated with the total injected energy and the energy density of the interstellar radiation field around PWNe. Except for the case of G292.0+1.8, broken power-law injection of the particles reproduces the broad-band emission from non-TeV PWNe well. © 2013 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. Source

Fujita Y.,Osaka University | Ohira Y.,Aoyama Gakuin University
Monthly Notices of the Royal Astronomical Society | Year: 2013

It has been proposed that the cool cores of galaxy clusters are stably heated by cosmic rays (CRs). If this is the case, radio mini-haloes, which are often found in the central regions of cool core clusters, may be attributed to the synchrotron emission from the CRs. Based on this idea, we investigate the radial profiles of the mini-haloes. First, usingnumerical simulations, we confirm that it is appropriate to assume that radiative cooling of the intracluster medium (ICM) is balanced with the heating by CR streaming. In these simulations, we assume that the streaming velocity of the CRs is the sound velocity of the ICM and indicate that the heating is even more stable than the case where the streaming velocity is the Alfvén velocity. Then, actually assuming the balance between cooling and heating, we estimate the radial profiles of CR pressure in six clusters only from X-ray observations. Since the CR protons interact with the ICM protons,we can predict the radial profiles of the resultant synchrotron radiation. We compare the predictions with the observed radial profiles of the mini-haloes in the six clusters and find that they are consistent if the momentum spectra of the CRs are steep. These results may indicate that the cores are actually being heated by the CRs. We also predict broad-band spectra of the six clusters and show that the non-thermal fluxes from the clusters are small in hard X-ray and gamma-ray bands. © 2012 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society. Source

Itani T.,EUVL Infrastructure Development Center Inc. | Kozawa T.,Osaka University
Japanese Journal of Applied Physics | Year: 2013

Extreme ultraviolet (EUV) radiation, the wavelength of which is 13.5 nm, is the most promising exposure source for next-generation semiconductor lithography. The development of EUV lithography has been pursued on a worldwide scale. Over the past decade, the development of EUV lithography has significantly progressed and approached its realization. In this paper, the resist materials and processes among the key technologies of EUV lithography are reviewed. Owing to its intensive development, the resist technology has already closely approached the requirements for the 22 nm node. The focus of the development has shifted to the 16nm node and beyond. Despite the trade-off relationships among resolution, line edge roughness/line width roughness, and sensitivity, the capability of resist technology will go beyond the 16nm node. © 2013 The Japan Society of Applied Physics. Source

Kitamura H.,Osaka University
International Journal of Industrial Organization | Year: 2010

This paper constructs a model of anticompetitive exclusive dealing in the presence of multiple entrants. Unlike the single-entrant model in previous literature, an entrant competes not only with the incumbent to deal with buyers but also with other entrants. The competition among entrants then serves as a commitment such that low wholesale prices are offered to buyers when they deviate from exclusive contracts. We argue that this commitment effect becomes a barrier to exclusive dealing and that the results differ drastically from the predictions of the single-entrant framework. © 2009 Elsevier B.V. All rights reserved. Source

Hirono T.,Osaka University | Tanikawa W.,Japan Agency for Marine - Earth Science and Technology
Earth and Planetary Science Letters | Year: 2011

Transient frictional heating during earthquake slip induces dehydroxylation of phyllosilicate minerals. As this reaction is endothermic and releases H2O, it affects dynamic fault weakening and the energetics of earthquakes. To quantitatively evaluate this effect, accurate determination of both the kinetic parameters of the reaction and the thermal properties of the minerals is needed. We chose an illite-muscovite sample as representative of the phyllosilicates found in active crustal faults. For this sample, we measured the specific heat capacity and thermal diffusivity, investigated their temperature dependencies, and determined the weight loss and enthalpy of the dehydroxylation reaction to be 5.22wt.% and 0.2895kJg-1, respectively. We applied Friedman analysis to the weight loss data from heating experiments and found that the dehydroxylation reactions were well fitted by two-step reactions of an n-dimensional nucleation mechanism according to the Avrami-Erofeev equation with n=0.5 (first step) and two-dimensional diffusion (second step). On the basis of these experimental results, we performed numerical analyses of dynamic fault weakening, which demonstrated that the fluids released by dehydroxylation contribute to pressurization of pore fluids inducing a decrease in effective normal stress on faults, and that the dehydroxylation reaction absorbs heat from the energy released. We also performed a sensitivity analysis on the kinetic function and parameters and the thermal properties, which showed that the contribution of these to fault weakening is considerably smaller than those of frictional coefficient and slip-zone thickness. © 2011 Elsevier B.V. Source

Nishiura H.,Osaka Institute of Technology | Fukuyama T.,Osaka University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2016

We propose a simple phenomenological model of quarks-leptons mass matrices having fundamentally universal symmetry structure. These mass matrices consist of democratic and semi-democratic mass matrix terms commonly to the neutrino and the quark sectors and have only eight free parameters. We show that this mass matrix model well reproduces all the observed values of the MNS lepton and the CKM quark mixing angles, the neutrino mass squared difference ratio, and quark mass ratios, with an excellent agreement. The model also predicts δCPℓ=-94° for the leptonic CP violating phase and 〈 m〉 ≃ 0.0073 eV for the effective Majorana neutrino mass. © 2015 The Authors. Source

Takata Y.,Osaka University
Cell structure and function | Year: 2011

Generation of iPS cells from mouse embryonic fibroblasts (MEF) was achieved using a BacMam transduction system containing a polycistronic plasmid expression vector for coincident and optimized expression of four defined reprogramming transcription factors. The sequences for Oct4, Klf4, Sox2 and c-Myc, were cloned as a fusion gene (OKSM) in a single open reading frame (ORF) via self-cleaving 2A peptides and expressed under the control of the CAG promoter. The transduction efficiency of primary MEF cells with BacMam particles carrying CAG-directed Venus reporter gene is 64-98%. After three successive transductions (at intervals of 3 days) of MEF cells with BacMam particles carrying a OKSM or OSKM cassette, the iPS cell colonies are observed in 15-24 days. A single transduction of MEF cells is also effective in generating sufficiently reprogrammed iPS cell lines. The iPS cell lines from colonies picked were positively stained by Nanog, SSEA-1 immunofluorescence and alkaline phosphatase substrate markers. The advantage of using the EOS-S(4+)-EmGFP reporter to identify sufficiently reprogrammed iPS cell lines is discussed by representing experimental results obtained with electroporated plasmids, such as a mixture of 2 tandem OS and KM plasmids and a polycistronic OKSM expression plasmid. Source

Delayed rupture is well-known as a severe complication after splenic injury treated with nonoperative management (NOM). The incidence and timing of splenic pseudoaneurysm (SPA) formation, which is a cause of delayed rupture following splenic injury, have not been thoroughly investigated, and the timing of follow-up computed tomography (CT) is controversial. The objective of this study was to clarify the incidence and timing of both the delayed formation and spontaneous resolution of SPA following splenic injuries treated with NOM in several trauma centers in Japan. This was a retrospective review of all patients with documented blunt splenic injury who were treated with NOM from 2003 through 2010 in five trauma and critical care centers. The present study consisted of 104 patients, including 16 patients (15.4%) with delayed formation of SPA (7 patients with Grade II and 9 with Grade III) during their clinical course. SPA was diagnosed with enhanced CT at a mean (SD) of 4.6 (2.1) hospital days (range, 1-8 days) after admission. Delayed formation of SPA was found in 30.4% of Grade II injuries and in 18.4% of Grade III injuries. Eight patients with delayed formation of SPA were observed without transcatheter arterial embolization during their entire stay. These SPAs were spontaneously occluded on follow-up enhanced CT or angiography. Spontaneous occlusion of SPA was confirmed at 5.2 (2.6) hospital days (range, 2-10 days) after diagnosis of delayed SPA. Delayed formation of SPAs was recognized with enhanced helical CT in 15% of all patients during hospital Days 1 to 8. About one half of the SPAs had occluded spontaneously without therapeutic intervention. Our results suggested that follow-up enhanced CT performed approximately 1 week after splenic injury may be useful to detect delayed SPA formation. Epidemiologic study, level III. Source

Sawa Y.,Osaka University
Surgery Today | Year: 2015

With the improvement in the overall life expectancy, the incidence of aortic stenosis has been increasing. Although aortic valve replacement is a standard therapy, many patients do not undergo surgery for various reasons, including advanced age or the presence of multiple comorbidities. Transcatheter aortic valve implantation (TAVI) has been proposed as a less invasive and equally effective treatment for inoperable or high-risk symptomatic aortic stenosis. Numerous rigorous global clinical trials, as well as a pivotal clinical trial in Japan, have been conducted. In this review, we provide data on the development of TAVI worldwide and discuss the prospects for TAVI in Japan. © 2014, Springer Japan. Source

An all-optical network still remains a long way from realistic deployment. However, all-optical packet switches, in which optical packets are buffered and routed in optical form, are still expected to solve the problems of electronic bottlenecks and large power consumption in electronic routers. An approximation is presented for blocking probabilities and delays of optical buffers, where optical packet arrival process is Poisson and packet-length distribution is general. The approximation aims at providing a simple calculation tool for optical buffer design without requiring computer simulations or extensive iterative computations. An approximation for the cumulative distribution function of the waiting time for general packet-length distributions was obtained that holds when the waiting time is sufficiently large and the traffic load is heavy. The difference in the blocking probabilities between the approximation and the simulation results was found to be less than 10% when the offered load was greater than 0.7. The approximation can be applied to investigate multiclass optical buffers for priority queueing and to design wavelength-division-multiplexing optical packet switches and networks with the maximum throughput. © 2011 IEEE. Source

Kawamura H.,Osaka University | Hatano T.,University of Tokyo | Kato N.,University of Tokyo | Biswas S.,Saha Institute of Nuclear Physics | Chakrabarti B.K.,Saha Institute of Nuclear Physics
Reviews of Modern Physics | Year: 2012

The present status of research and understanding regarding the dynamics and the statistical properties of earthquakes is reviewed, mainly from a statistical physical viewpoint. Emphasis is put both on the physics of friction and fracture, which provides a microscopic basis for our understanding of an earthquake instability, and on the statistical physical modelling of earthquakes, which provides macroscopic aspects of such phenomena. Recent numerical results from several representative models are reviewed, with attention to both their critical and their characteristic properties. Some of the relevant notions and related issues are highlighted, including the origin of power laws often observed in statistical properties of earthquakes, apparently contrasting features of characteristic earthquakes or asperities, the nature of precursory phenomena and nucleation processes, and the origin of slow earthquakes, etc. © 2012 American Physical Society. Source

Koide Y.,Osaka University | Nishiura H.,Osaka Institute of Technology
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

A new yukawaon model is investigated under a family symmetry U(3)×S 3. In this model, all vacuum expectation values (VEVs) of the yukawaons, 〈Y f〉, are described in terms of a fundamental VEV matrix 〈Φ 0〉 as in the previous yukawaon model, but the assignments of quantum number for fields are different from the previous ones: the fundamental yukawaon Φ 0 is assigned to (3, 3) of U(3)×U(3), which is broken into (3, 1+2) of U(3)×S 3, although quarks and leptons are still assigned to triplets of U(3) and yukawaons Y f are assigned to 6 * of U(3). Then, VEV relations among yukawaons become more concise considerably than the previous yukawaon models. By adjusting parameters, we can fit not only quark mixing parameters but also lepton mixing parameters together with their mass ratios. © 2012 Elsevier B.V. Source

Kushibiki T.,Osaka University
Journal of Biophotonics | Year: 2010

Apoptosis-related microRNAs (miRNAs), the expression levels of which were observed to increase after photodynamic therapy (PDT), were identified as markers of PDT efficacy. miRNAs form a class of small endogenous RNAs that play important regulatory roles by targeting mRNA for cleavage or translational repression. miRNAs contribute to diverse biological processes, including development, cell growth, apoptosis, and hematopoiesis, which suggests a role in cancer development. However, no previous reports have described a relationship between apoptosis and miRNA expression after PDT. In this study, apoptosis-related miRNA levels were characterized by real-time PCR after PDT in HeLa cells. miR-210 and miR-296 expression levels increased 1 hour after PDT, although the other apoptosis-related miRNA (miR-7, miR-148a, miR-204, and miR-216) expression levels were unchanged. Since miR-210 is the most prominent miRNA consistently stimulated under hypoxic conditions and VEGF is capable of increasing miR-296 expression levels, these data suggest that hypoxia induced by PDT induces miR-210 expression, followed by an increase of VEGF expression and miR-296 expression. These results constitute the first report of an analysis of miRNA expression after PDT using talaporfin sodium as a photosensitizer, demonstrating that miR-210 and miR-296 expression levels are markers of PDTefficacy in HeLa cells. © 2010 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Rubin and Thayer (Psychometrika, 47:69-76, 1982) proposed the EM algorithm for exploratory and confirmatory maximum likelihood factor analysis. In this paper, we prove the following fact: the EM algorithm always gives a proper solution with positive unique variances and factor correlations with absolute values that do not exceed one, when the covariance matrix to be analyzed and the initial matrices including unique variances and inter-factor correlations are positive definite. We further numerically demonstrate that the EM algorithm yields proper solutions for the data which lead the prevailing gradient algorithms for factor analysis to produce improper solutions. The numerical studies also show that, in real computations with limited numerical precision, Rubin and Thayer's (Psychometrika, 47:69-76, 1982) original formulas for confirmatory factor analysis can make factor correlation matrices asymmetric, so that the EM algorithm fails to converge. However, this problem can be overcome by using an EM algorithm in which the original formulas are replaced by those guaranteeing the symmetry of factor correlation matrices, or by formulas used to prove the above fact. © 2012 The Psychometric Society. Source

Sekihara T.,Osaka University | Oset E.,University of Valencia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study the semileptonic decays of Ds+, D+, and D0 mesons into the light scalar mesons [f0(500), K0∗(800), f0(980), and a0(980)] and the light vector mesons [ρ(770), ω(782), K∗(892), and φ(1020)]. With the help of a chiral unitarity approach in coupled channels, we compute the branching fractions for scalar meson processes of the semileptonic D decays in a simple way. Using current known values of the branching fractions, we make predictions for the branching fractions of the semileptonic decay modes with other scalar and vector mesons. Furthermore, we calculate the π+π-, πη, πK, and K+K- invariant mass distributions in the semileptonic decays of D mesons, which will help us clarify the nature of the light scalar mesons. © 2015 American Physical Society. © 2015 American Physical Society. Source

Nagasaki K.,University of Tokyo | Yamaguchi S.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We consider a 2-dimensional conformal field theory (CFT) obtained from twisted compactification of the 4-dimensional N=4 super Yang-Mills theory on a Riemann surface with a boundary. We find the boundary conditions for preserving some of the supersymmetry. In particular, an N=(2,2) superconformal field theory is obtained from supersymmetry breaking due to the boundary from N=(4,4). In this case we calculate the central charge of the CFT and show its dependence on the topology of the Riemann surface. © 2015 American Physical Society. Source

Togashi Y.,Osaka University
PLoS computational biology | Year: 2010

The assumption of linear response of protein molecules to thermal noise or structural perturbations, such as ligand binding or detachment, is broadly used in the studies of protein dynamics. Conformational motions in proteins are traditionally analyzed in terms of normal modes and experimental data on thermal fluctuations in such macromolecules is also usually interpreted in terms of the excitation of normal modes. We have chosen two important protein motors--myosin V and kinesin KIF1A--and performed numerical investigations of their conformational relaxation properties within the coarse-grained elastic network approximation. We have found that the linearity assumption is deficient for ligand-induced conformational motions and can even be violated for characteristic thermal fluctuations. The deficiency is particularly pronounced in KIF1A where the normal mode description fails completely in describing functional mechanochemical motions. These results indicate that important assumptions of the theory of protein dynamics may need to be reconsidered. Neither a single normal mode nor a superposition of such modes yields an approximation of strongly nonlinear dynamics. Source

Hashiguchi K.,Osaka University
Archives of Computational Methods in Engineering | Year: 2015

The subloading surface model is endowed with the intrinsic far-reaching ability to describe the wide classes of irreversible mechanical behavior, e.g. the monotonic and the cyclic loading behavior of elastoplastic and viscoplastic materials, the friction behavior and the crystal plastic behavior as has been examined in the former paper (Hashiguchi in Arch Comput Methods Eng 20:361–417, 2013). However, the past formulations of the subloading surface model have contained several inexact equations, which have been modified repeatedly since the concept of the subloading surface was proposed in 1977 (Hashiguchi and Ueno 1977). The exact formulation is presented first in this article for the hypoelastic-based plasticity, which enjoys the distinguished superiority in the both aspects of the description of material behavior in high accuracy and of the numerical calculation in high efficiency. It is further provided for all the four basic frameworks, i.e. the infinitesimal hypoelastic-based plasticity, the infinitesimal hyperelastic-based plasticity, the hypoelastic-based plasticity and the multiplicative hyperelastic-based plasticity for finite strain. Further, the subloading-crystal plasticity model is formulated modifying the former one (Hashiguchi 2013) by incorporating the decomposition of the crystalline shear strain rate into the elastic and the plastic parts. This would be the guidebook to the subloading surface model and also the memorial monograph for the historical development of the subloading surface model. © 2015 CIMNE, Barcelona, Spain Source

Sun-Wada G.-H.,Doshisha Womans College | Wada Y.,Osaka University
Histology and Histopathology | Year: 2013

Vacuolar H+-translocating ATPase (VATPase) is a universal proton pump, and its activity is required for a variety of cell biological processes, such as membrane trafficking, receptor-mediated endocytosis, lysosomal degradation of macromolecules, osteoclastic bone resorption, and the maintenance of acid-base homeostasis by renal intercalated cells. V-ATPase is targeted to various membranes and has different compositions depending on its cellular location. Here, we focus on recent knowledge concerning the targeting mechanism of V-ATPase, a process associated with a wide spectrum of diseases. We also discuss the functions of this enzyme in macrophages and cancer cells-2 characteristic cell types with clinical importance. Source

Sawa Y.,Osaka University
General Thoracic and Cardiovascular Surgery | Year: 2013

Myocardial regeneration therapy has emerged as an alternative therapy for heart failure and is expected to replace current conventional therapies. As a cell source, the presence of resident cardiac stem cells (RCSC) in the heart has been reported by many researchers. These RCSC show multi-potency and are considered to differentiate into myocytes. On the other hand, bone marrow stem cells have received the greatest attention as a source of cell transplantation therapy in the current era, with a larger number of clinical applications reported because of their ease and safety. Myoblasts have also emerged as a possible cell source for clinical applications. We previously found that myoblast-cell-sheet implantation improved cardiac function and ventricle thickness in a rat MI model. Furthermore, we conducted a pre-clinical large animal study using porcine MI and dog DCM models, and confirmed the effectiveness of skeletal myoblast sheets. Thereafter, we conducted clinical applications of skeletal myoblast implantation. It may eventually be possible to perform regeneration therapy as a routine therapeutic method. © 2012 The Japanese Association for Thoracic Surgery. Source

Inui S.,Osaka University
Journal of Dermatology | Year: 2011

In recent years, the usefulness of trichoscopy (scalp dermoscopy) has been reported for hair loss diseases. Here, characteristic trichoscopic features of common hair loss diseases are described using a DermLite II pro or Epilight eight. Characteristic trichoscopic features of alopecia areata are black dots, tapering hairs (exclamation mark hairs), broken hairs, yellow dots and short vellus hairs. In androgenetic alopecia (AGA), hair diameter diversity (HDD), perifollicular pigmentation/peripilar sign and yellow dots are trichoscopically observed. In all cases of AGA and female AGA, HDD more than 20%, which corresponds to vellus transformation, can be seen. In cicatricial alopecia (CA), the loss of orifices, a hallmark of CA, and the associated changes including perifollicular erythema or scale and hair tufting were observed. Finally, an algorithmic method for trichoscopic diagnosing is proposed. © 2011 Japanese Dermatological Association. Source

Kuno Y.,Osaka University
Nuclear Physics B - Proceedings Supplements | Year: 2012

The experiment (COMET) at J-PARC to search for a charged-lepton-flavor-violating process of muon to electron conversion in a muonic atom is described. Future prospects of an experiment (PRISM) with even higher sensitivity is mentioned. On-going R&D on a highly intense muon source (MuSIC) at Osaka University is presented. © 2012 Elsevier B.V. Source

Yasuda T.,Osaka University
Molecular neurobiology | Year: 2013

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting ~1 % of people over the age of 65. Neuropathological hallmarks of PD are prominent loss of dopaminergic (DA) neurons in the substantia nigra and formation of intraneuronal protein inclusions termed Lewy bodies, composed mainly of α-synuclein (αSyn). Missense mutations in αSyn gene giving rise to production of degradation-resistant mutant proteins or multiplication of wild-type αSyn gene allele can cause rare inherited forms of PD. Therefore, the existence of abnormally high amount of αSyn protein is considered responsible for the DA neuronal death in PD. Normally, αSyn protein localizes to presynaptic terminals of neuronal cells, regulating the neurotransmitter release through the modulation of assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex. On the other hand, of note, pathological examinations on the recipient patients of fetal nigral transplants provided a prion-like cell-to-cell transmission hypothesis for abnormal αSyn. The extracellular αSyn fibrils can internalize to the cells and enhance intracellular formation of protein inclusions, thereby reducing cell viability. These findings suggest that effective removal of abnormal species of αSyn in the extracellular space as well as intracellular compartments can be of therapeutic relevance. In this review, we will focus on αSyn-triggered neuronal cell death and provide possible disease-modifying therapies targeting abnormally accumulating αSyn. Source

Sekihara T.,Osaka University | Kumano S.,High Energy Accelerator Research Organization
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

The structure of the a0(980) and f0(980) resonances is investigated with the a0(980)-f0(980) mixing intensity from the viewpoint of compositeness, which corresponds to the amount of two-body states composing resonances as well as bound states. For this purpose, we first formulate the a0(980)-f0(980) mixing intensity as the ratio of two partial decay widths of a parent particle, in the same manner as the recent analysis in BES experiments. Calculating the a0(980)-f0(980) mixing intensity with the existing Flatte parameters from experiments, we find that many combinations of the a0(980) and f0(980) Flatte parameters can reproduce the experimental value of the a0(980)-f0(980) mixing intensity by BES. Next, from the same Flatte parameters, we also calculate the KK¯ compositeness for a0(980) and f0(980). Although the compositeness with the correct normalization becomes complex in general for resonance states, we find that the Flatte parameters for f0(980) imply a large absolute value of the KK¯ compositeness, and the parameters for a0(980) lead to a small but non-negligible absolute value of the KK¯ compositeness. Then, connecting the mixing intensity and the KK¯ compositeness via the a0(980)- and f0(980)-KK¯ coupling constants, we establish a relation between them. As a result, a small mixing intensity indicates a small value of the product of the KK¯ compositeness for the a0(980) and f0(980) resonances. Moreover, the experimental value of the a0(980)-f0(980) mixing intensity implies that the a0(980) and f0(980) resonances cannot be simultaneously KK¯ molecular states. © 2015 American Physical Society. Source

Nakano H.,Osaka University
Journal of Materials Chemistry | Year: 2010

A photochromic molecular fiber was developed and the photomechanical bending motions of the fiber were demonstrated. The bending direction of the fiber was found to be controllable by altering the polarization direction of the irradiated light without changing the position of the light source and the wavelength of the light. © 2010 The Royal Society of Chemistry. Source

Kumar R.,Iowa State University | Takai S.,Osaka University
IEEE Transactions on Automatic Control | Year: 2010

We study the prognosis of failures, i.e., their prediction prior to their occurrence, in discrete event systems in a decentralized setting where multiple prognosers use their local observations to issue local prognosis decisions. We define the notion of correctness of a decentralized set of prognosers in terms of no missed detections (each failure is prognosed prior to its occurrence) and no false alarms (an incorrect prognostic decision is never issued), and introduce the notion of coprognosability as an existence condition. When specialized to the centralized case (i.e., the case of a single prognoser), this condition turns out to be weaker than the one introduced by Genc and Lafortune in 2006 since a uniform bound on the number of steps within which a failure will occur is not required. For comparison, we also introduce the stronger notion of uniformly bounded coprognosability and identify the subclass of decentralized prognosers for which it serves as an existence condition. We show that the two notions coincide when the underlying system and its nonfailure specification possess finite-state representations, and present a verification algorithm whose complexity is polynomial in the sizes of the system being prognosed and its nonfailure specification, and is exponential in the number of the local prognosers. We also introduce the notion of reaction bound for coprognosis as the earliest time beyond a prognostic decision when a failure can occur, and present an algorithm for computing it. The complexity of this algorithm is identical to that of the verification algorithm. An algorithm with complexity linear in the size of the specification and the number of local prognosers is also presented for an online prognosis of failures. We show that the notions of coprognosability and its uniformly bounded version are in general incomparable with the notion of codiagnosability (that guarantees a uniformly bounded delay detection of a failure by a local diagnoser). When the system cannot execute an unbounded sequence of unobservable events, uniformly bounded coprognosability implies codiagnosability, whereas coprognosability and codiagnosability remain incomparable. © 2009 IEEE. Source

The aim of this study was to investigate the association of masticatory ability and dental status with intake of fruits and vegetables after adjusting for other factors in independently living elderly Japanese subjects. The study population consisted of 1,535 community-dwelling, independent elderly subjects over the age of 60 years. Self-assessed general health, financial status, dental status, self-assessed masticatory ability by food acceptance, and frequency of food intake were evaluated from responses to a questionnaire. Multiple logistic regression analysis for shortage of food intake was carried out. Of the participants, 29% had natural dentitions in both the maxilla and mandible and 15% were edentulous in at least one arch and wearing a complete denture. Percentages of participants with nutrient shortages of meat, fish and seafood, green and yellow vegetables, other vegetables, and fruits were 44%, 17%, 30%, 33%, and 12%, respectively. Multiple logistic regression analysis showed that men and subjects with a poor financial status had significant associations with shortages of dietary intake. In addition, shortages of meat, green and yellow vegetables, other vegetables, and fruit were significantly related to poor masticatory ability but not to dental status. Masticatory ability was significantly associated with shortages of green and yellow vegetables. Multivariate analyses showed that after adjusting for age, sex, and financial status, self-assessed masticatory ability rather than dental status by itself was significantly associated with shortages in vegetable and fruit intake in independently living elderly Japanese subjects. Source

Ezoe S.,Osaka University
International Journal of Environmental Research and Public Health | Year: 2012

Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL) gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia. © 2012 by the authors. licensee MDPI, Basel, Switzerland. Source

Many people suffer from metal allergy, and the recently demonstrated presence of naturally occurring metal nanoparticles in our environment could present a new candidate for inducing metal allergy. Here, we show that mice pretreated with silver nanoparticles (nAg) and lipopolysaccharides, but not with the silver ions that are thought to cause allergies, developed allergic inflammation in response to the silver. nAg-induced acquired immune responses depended on CD4+ T cells and elicited IL-17A-mediated inflammation, similar to that observed in human metal allergy. Nickel nanoparticles also caused sensitization in the mice, whereas gold and silica nanoparticles, which are minimally ionizable, did not. Quantitative analysis of the silver distribution suggested that small nAg (≤10 nm) transferred to the draining lymph node and released ions more readily than large nAg (>10 nm). These results suggest that metal nanoparticles served as ion carriers to enable metal sensitization. Our data demonstrate a potentially new trigger for metal allergy. © 2016 Nature Publishing Group Source

Kurosaki T.,Osaka University | Kurosaki T.,RIKEN
Molecular Immunology | Year: 2011

B cells and antibodies are important elements of acquired humoral immunity in the fight against various pathogens, and signals through the B cell receptor (BCR) are crucial for the development, activation and differentiation of B cells. Our laboratory has focused on understanding the molecular mechanisms of BCR-mediated signaling cascades that regulate these processes in B cells. In this review, I will briefly present our studies that have clarified the molecular components of signaling cascades, mainly focusing on data using DT40 B cells and their genetic variants. © 2010 Elsevier Ltd. Source

Neutrophils contribute to pathogen clearance by producing neutrophil extracellular traps (NETs), which are genomic DNA-based net-like structures that capture bacteria and fungi. Although NETs also express antiviral factors, such as myeloperoxidase and α-defensin, the involvement of NETs in antiviral responses remains unclear. We show that NETs capture human immunodeficiency virus (HIV)-1 and promote HIV-1 elimination through myeloperoxidase and α-defensin. Neutrophils detect HIV-1 by Toll-like receptors (TLRs) TLR7 and TLR8, which recognize viral nucleic acids. Engagement of TLR7 and TLR8 induces the generation of reactive oxygen species that trigger NET formation, leading to NET-dependent HIV-1 elimination. However, HIV-1 counteracts this response by inducing C-type lectin CD209-dependent production of interleukin (IL)-10 by dendritic cells to inhibit NET formation. IL-10 suppresses the reactive oxygen species-dependent generation of NETs induced upon TLR7 and TLR8 engagement, resulting in disrupted NET-dependent HIV-1 elimination. Therefore, NET formation is an antiviral response that is counteracted by HIV-1. Copyright © 2012 Elsevier Inc. All rights reserved. Source

Kim A.,Osaka University
Journal of experimental & clinical cancer research : CR | Year: 2012

Ovarian cancer is the most lethal gynecologic malignancy. It appears that the vast majority of what seem to be primary epithelial ovarian and primary peritoneal carcinomas is, in fact, secondary from the fimbria, the most distal part of the fallopian tube. Treatment of epithelial ovarian cancer is based on the combination of cytoreductive surgery and combination chemotherapy using taxane and platinum. Although clear cell type is categorized in indolent type, it is known to show relatively strong resistance to carboplatin and paclitaxel regimen and thus poor prognosis compared to serous adenocarcinoma, especially in advanced stages. Irinotecan plus cisplatin therapy may effective for the clear cell adenocarcinoma. The larger expectation for improved prognosis in ovarian carcinoma is related to the use of the new biological agents. One of the most investigated and promising molecular targeted drugs in ovarian cancer is bevacizumab, a monoclonal antibody directed against VEGF. PARP inhibitor is another one. A few recent studies demonstrated positive results of bevacizumab on progression-free survival in ovarian cancer patients, however, investigation of molecular targeting drugs in patients with ovarian cancer are still underway. Source

Inui S.,Osaka University
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: Severe pruritus associated with end-stage renal disease is a particularly troublesome complication, because no effective treatment has been established. However, based on the findings of a recent randomized controlled trial, nalfurafine hydrochloride was officially approved in Japan for the treatment of resistant pruritus in hemodialysis patients. Areas covered: This review is based upon a PubMed search and personal experience with nalfurafine hydrochloride. The pharmacokinetics and pharmacodynamics of nalfurafine hydrochloride are reviewed and its efficiency and potential adverse effects are discussed, mainly based on the findings of randomized controlled trials. Expert opinion: A recent long-term open trial showed that the effect of nalfurafine hydrochloride was enhanced by continuous, long-term administration. It will be of future interest to investigate its effect on excoriations, lichen simplex, prurigo nodularis and acquired perforating dermatosis (all caused by uremic pruritus), because it targets both the skin and the central nervous system. In clinical practice, it should be kept in mind that basic skin care with emollients and other topical drugs is essential for stopping the itchscratch cycle, and the resultant skin barrier dysfunction. © 2012 Informa UK, Ltd. Source

Multiple transcription factors (TFs) are involved in the generation of gene expression patterns, such as tissue-specific gene expression and pleiotropic immune responses. However, how combinations of TFs orchestrate diverse gene expression patterns is poorly understood. Here we propose a new measure for regulatory motif co-occurrence and a new methodology to systematically identify TF pairs significantly co-occurring in a set of promoter sequences. Initial analyses suggest that non-CpG promoters have a higher potential for combinatorial regulation than CpG island-associated promoters, and that co-occurrences are strongly influenced by motif similarity. We applied our method to large-scale gene expression data from various tissues, and showed how our measure for motif co-occurrence is not biased by motif over-representation. Our method identified, amongst others, the binding motifs of HNF1 and FOXP1 to be significantly co-occurring in promoters of liver/kidney specific genes. Binding sites tend to be positioned proximally to each other, suggesting interactions exist between this pair of transcription factors. Moreover, the binding sites of several TFs were found to co-occur with NF-κB and IRF sites in sets of genes with similar expression patterns in dendritic cells after Toll-like receptor stimulation. Of these, we experimentally verified that CCAAT enhancer binding protein alpha positively regulates its target promoters synergistically with NF-κB. Both computational and experimental results indicate that the proposed method can clarify TF interactions that could not be observed by currently available prediction methods. Source

Nam W.,Ewha Womans University | Lee Y.-M.,Ewha Womans University | Fukuzumi S.,Ewha Womans University | Fukuzumi S.,Osaka University
Accounts of Chemical Research | Year: 2014

ConspectusMononuclear nonheme iron enzymes generate high-valent iron(IV)-oxo intermediates that effect metabolically important oxidative transformations in the catalytic cycle of dioxygen activation. In 2003, researchers first spectroscopically characterized a mononuclear nonheme iron(IV)-oxo intermediate in the reaction of taurine: α-ketogultarate dioxygenase (TauD). This nonheme iron enzyme with an iron active center was coordinated to a 2-His-1- carboxylate facial triad motif. In the same year, researchers obtained the first crystal structure of a mononuclear nonheme iron(IV)-oxo complex bearing a macrocyclic supporting ligand, [(TMC)Fe IV(O)]2+ (TMC = 1,4,8,11-tetramethyl-1,4,8,11- tetraazacyclotetradecene), in studies that mimicked the biological enzymes. With these breakthrough results, many other studies have examined mononuclear nonheme iron(IV)-oxo intermediates trapped in enzymatic reactions or synthesized in biomimetic reactions. Over the past decade, researchers in the fields of biological, bioinorganic, and oxidation chemistry have extensively investigated the structure, spectroscopy, and reactivity of nonheme iron(IV)-oxo species, leading to a wealth of information from these enzymatic and biomimetic studies.This Account summarizes the reactivity and mechanisms of synthetic mononuclear nonheme iron(IV)-oxo complexes in oxidation reactions and examines factors that modulate their reactivities and change their reaction mechanisms. We focus on several reactions including the oxidation of organic and inorganic compounds, electron transfer, and oxygen atom exchange with water by synthetic mononuclear nonheme iron(IV)-oxo complexes. In addition, we recently observed that the C-H bond activation by nonheme iron(IV)-oxo and other nonheme metal(IV)-oxo complexes does not follow the H-atom abstraction/oxygen-rebound mechanism, which has been well-established in heme systems.The structural and electronic effects of supporting ligands on the oxidizing power of iron(IV)-oxo complexes are significant in these reactions. However, the difference in spin states between nonheme iron(IV)-oxo complexes with an octahedral geometry (with an S = 1 intermediate-spin state) or a trigonal bipyramidal (TBP) geometry (with an S = 2 high-spin state) does not lead to a significant change in reactivity in biomimetic systems. Thus, the importance of the high-spin state of iron(IV)-oxo species in nonheme iron enzymes remains unexplained. We also discuss how the axial and equatorial ligands and binding of redox-inactive metal ions and protons to the iron-oxo moiety influence the reactivities of the nonheme iron(IV)-oxo complexes. We emphasize how these changes can enhance the oxidizing power of nonheme metal(IV)-oxo complexes in oxygen atom transfer and electron-transfer reactions remarkably. This Account demonstrates great advancements in the understanding of the chemistry of mononuclear nonheme iron(IV)-oxo intermediates within the last 10 years. © 2014 American Chemical Society. Source

BACKGROUND:: Haloperidol has immunomodulatory effects when used to treat patients with schizophrenia and also is used to sedate critically ill patients in the intensive care unit. Although the mechanism by which haloperidol affects immune function is unclear, one possibility is that it alters dendritic cell (DC) function. DCs are potent antigen-presenting cells that influence the activation and maturation of T lymphocytes. In this study, we investigated the in vitro and in vivo immunomodulatory effects of haloperidol on DC-mediated immune responses.METHODS:: Using bone marrow–derived DCs in cell culture, we evaluated the effect of haloperidol on expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class ΙІ molecules, and the DC maturation marker CD83. DC culture supernatants also were evaluated for interleukin-12 p40 levels. In addition, we analyzed the effect of haloperidol on a mixed cell culture containing DCs and lymphocytes and measured the secretion of interferon-γ in the culture supernatants. We also assessed the in vivo effects of haloperidol on hapten-induced contact hypersensitivity responses.RESULTS:: Haloperidol inhibited the expression of CD80, CD86, major histocompatibility complex class ΙІ, and CD83 molecules on DCs and the secretion of interleukin-12p40 in DC culture supernatants. In mixed cell cultures containing both T cells (CD4 and CD8α) and DCs, haloperidol-treated DCs suppressed the proliferation of allogeneic T cells and effectively inhibited the production of interferon-γ. In vivo, haloperidol reduced hapten-induced contact hypersensitivity responses. Furthermore, an antagonist to D2-like receptor suppressed the maturation of DCs in a manner similar to haloperidol.CONCLUSIONS:: The results of our study suggest that haloperidol suppresses the functional maturation of DCs and plays an important role in the inhibition of DC-induced T helper 1 immune responses in the whole animal. Furthermore, the effect of haloperidol on DCs may be mediated by dopamine D2–like receptors. Together, these results demonstrate that administration of haloperidol suppresses DC-mediated immune responses. © 2015 International Anesthesia Research Society Source

Extensive studies on the structure of collagen have revealed that the hydroxylation of Pro residues in a variety of model peptides with the typical (X-Y-Gly)(n) repeats (X and Y: Pro and its analogues) represents one of the major factors influencing the stability of triple helices. While(2S,4R)-hydroxyproline (Hyp) at the position Y stabilizes the triple helix, (2S,4S)-hydroxyproline (hyp) at the X-position destabilizes the helix as demonstrated that the triple helix of (hyp-Pro-Gly)(15) is less stable than that of (Pro-Pro-Gly)(15) and that a shorter peptide (hyp-Pro-Gly)(10) does not form the helix. To clarify the role of the hydroxyl group of Pro residues to play in the stabilization mechanism of the collagen triple helix, we synthesized and crystallized a model peptide (Pro-Hyp-Gly)(4) -(hyp-Pro-Gly)(2) -(Pro-Hyp-Gly)(4) and analyzed its structure by X-ray crystallography and CD spectroscopy. In the crystal, the main-chain of this peptide forms a typical collagen like triple helix. The majority of hyp residues take down pucker with exceptionally shallow angles probably to relieve steric hindrance, but the remainders protrude the hydroxyl group toward solvent with the less favorable up pucker to fit in a triple helix. There is no indication of the existence of an intra-molecular hydrogen bond between the hydroxyl moiety and the carbonyl oxygen of hyp supposed to destabilize the triple helix. We also compared the conformational energies of up and down packers of the pyrrolidine ring in Ac-hyp-NMe(2) by quantum mechanical calculations. Copyright © 2011 Wiley Periodicals, Inc. Source

The fact that acute phase proteins, such as C-reactive protein (CRP) and serum amyloid A (SAA), are elevated during inflammation is known to nearly all medical practitioners. However, exact mechanism for induction of these acute phase proteins, both in vitro and in vivo, remains unknown. IL-6 induces inflammatory status in autoimmune diseases. Consequently, IL-6 blocking therapy with an anti-IL-6 receptor antibody (tocilizumab) for Castleman's disease (CD) [1, 2], rheumatoid arthritis (RA) [3], and juvenile idiopathic arthritis (JIA) [4] led to improvement in most clinical symptoms and laboratory findings. CRP and SAA levels in particular were reduced and completely normalized, even if another cytokines and chemokines were activated in patients with RA. On the other hand, single use of TNF-α blockers, such as infliximab or etanercept, reduced SAA and CRP levels in RA patients, but barely to within normal range [5]. In this study, to clarify the different pathologic roles of IL-6 and TNF-α or IL-1 in induction of SAA and CRP in chronic inflammatory disease, we used hepatoma-derived cell lines to analyze the difference between the IL-6 and TNF-α mechanism in vitro, and between IL-6 and TNF-α blocking therapy for RA in vivo. © 2011 Springer Science+Business Media, LLC. Source

Minamino T.,Osaka University | Kitakaze M.,Japan National Cardiovascular Center Research Institute
Journal of Molecular and Cellular Cardiology | Year: 2010

The endoplasmic reticulum (ER) is an organelle involved in protein folding, calcium homeostasis, and lipid biosynthesis. Various factors that interfere with ER function lead to accumulation of unfolded proteins, including oxidative stress, ischemia, disturbance of calcium homeostasis, and overexpression of normal and/or incorrectly folded proteins. The resulting ER stress triggers the unfolded protein response (UPR) that induces signal transduction events to reduce the accumulation of unfolded proteins by increasing ER resident chaperones, inhibiting protein translation, and accelerating the degradation of unfolded proteins. However, if stress is severe and/or prolonged, the ER also initiates apoptotic signaling that includes induction of the pro-apoptotic transcriptional factor C/EBP homologous protein, activation of c-Jun amino-terminal kinase, and cleavage of caspase-12. These ER-initiated events lead to cell death via mitochondria-dependent and -independent apoptotic pathways. Furthermore, the B cell lymphoma 2 family of proteins expressed on the ER and mitochondria are also involved in regulating cell death due to ER stress. Thus, the ER is now recognized as a vitally important organelle that can decide cell survival or death. Recent animal and human studies have revealed that the UPR and ER-initiated apoptosis are implicated in the pathophysiology of various cardiovascular diseases, including heart failure, ischemic heart disease, the development of atherosclerosis, and plaque rupture. Improved understanding of the molecular mechanisms underlying UPR activation and ER-initiated apoptosis in cardiovascular disease will provide us with new targets for drug discovery and therapeutic intervention. © 2009 Elsevier Ltd. Source

Because of the difficulties of low sensitivity for anticancer agents and giving a sufficient dose because of chronic liver dysfunction, chemotherapy may not play a central role in the treatment of hepatocellular carcinoma (HCC), especially those with liver cirrhosis. However, chemotherapy must be one of the important possibilities of multimodal treatment for advanced HCC, for which hepatic resection, percutaneous ablation, transcatheter arterial embolization and other general therapies would not be effective or even possible. Also, intraarterial perfusion chemotherapy is a common therapy for HCC and it is not difficult to maintain; but the effective rate is not sufficient. Recently, the combination therapy of subcutaneous interferon (IFN)-α and intraarterial 5-fluorouracil (5-FU) showed an outstanding response rate for intractable HCC (with portal vein thrombosis). In addition, recent preclinical and clinical studies have revealed that the mechanism of combination therapy may concern direct antitumor effects (through cell-cycle arrest and induction of apoptosis) and indirect actions (through immunocompetent cells and antiangiogenic effect). For the further advance of HCC treatment and prognosis, this therapy might be a promising treatment modality and is expected to develop. In this review, we summarize recent clinical and preclinical data regarding IFN-α and 5-FU combination therapy and discuss the further prospects of this therapy. Copyright © 2010 S. Karger AG. Source

Sakaguchi S.,Osaka University | Sakaguchi S.,Kyoto University | Powrie F.,University of Oxford | Ransohoff R.M.,Cleveland Clinic Lerner Research Institute
Nature Medicine | Year: 2012

Recent progress has revealed the molecular basis of how self-reactive T cells are normally generated in the immune system and differentiate into autoimmune effector T cells and how they are controlled by central and peripheral mechanisms of self-tolerance. There is also evidence that target tissues and cells in autoimmune disease have different sensitivities to immune mediators. Here we describe how these basic findings can be clinically translated to re-establish self-tolerance in individuals with autoimmune disease. © 2012 Nature America, Inc. All rights reserved. Source

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

We discuss the uniqueness or nonuniqueness problem of the decomposition of the gluon field into the physical and pure-gauge components, which is the basis of the two recently proposed physically inequivalent gauge-invariant decompositions of the nucleon spin. It is crucially important to recognize the fact that the standard gauge-fixing procedure is essentially a process of projecting out the physical components of the massless gauge field. A complexity of the non-Abelian gauge theory as compared with the Abelian case is that a closed expression for the physical component can be given only with use of the nonlocal Wilson line, which is generally path dependent. It is known that - by choosing an infinitely long straight-line path in space and time, the direction of which is characterized by a constant four-vector nμ - one can cover a class of gauge called the general axial gauge, containing three popular gauges, i.e., the temporal, the light-cone, and the spatial axial gauge. Within this general axial gauge, we calculate the one-loop evolution matrix for the quark and gluon longitudinal spins in the nucleon. We find that the final answer is exactly the same independent of the choices of nμ, which amounts to proving the gauge independence and path independence simultaneously, although within a restricted class of gauges and paths. By drawing on all of these findings together with well-established knowledge from gauge theories, we argue against the rapidly spreading view in the community that there are infinitely many decompositions of the nucleon spin. © 2013 American Physical Society. Source

Ajiki H.,Osaka University
Journal of the Physical Society of Japan | Year: 2013

A new method for calculating exciton wavefunctions in the presence of a long-range electron-hole (e-h) exchange interaction (EXI) is presented. The e-h EXI arises, for example, for cross-polarized excitons in a single-walled carbon nanotube (SWNT). Cross-polarized excitons have previously been calculated as an eigenvalue problem of a Bethe- Salpeter equation (BSE) within the Tamm-Dancoff-type approximation (TDA). The resulting wavefunctions provide quite different absorption spectra in comparison with those calculated in the self-consistent-field method [S. Uryu and T. Ando, J. Phys.: Conf. Ser. 302 (2011) 012004]. Although the self-consistent-field method is more reliable, exciton wavefunctions cannot be obtained from this method. A general method is derived here to obtain exciton wavefunctions that take the e-h EXI into account within the TDA, and the method is applied to the cross-polarized excitons of a SWNT. The absorption spectra calculated from the resulting exciton wavefunctions agree well with the spectra calculated from the self-consistent-field method within a rotating-wave approximation. © 2013 The Physical Society of Japan. Source

Yamauchi K.,Osaka University
Journal of the Physical Society of Japan | Year: 2013

By means of symmetry analysis and density-functional calculations, both the crystal structure and the sizable ferroelectric polarization are predicted in A-site ordered half-doped manganite SmBaMn2O6. It is shown that the ferroelectricity is determined by apical oxygen displacement, which involves MnO6 octahedral tilt mode. Furthermore, an analysis of the link between the ferroelectricity and the rare earth ionic size in the manganite series is carried out, in the aim of clarifying the chemical trend. The computational result quantitatively shows that the relatively small rare earth ion with respect to Ba ion enhances the ferroelectric polarization up to order of several μC/cm2. © 2013 The Physical Society of Japan. Source

Kawahara G.,Osaka University | Uhlmann M.,Karlsruhe Institute of Technology | Van Veen L.,University of Ontario Institute of Technology
Annual Review of Fluid Mechanics | Year: 2011

Recent remarkable progress in computing power and numerical analysis is enabling us to fill a gap in the dynamical systems approach to turbulence. A significant advance in this respect has been the numerical discovery of simple invariant sets, such as nonlinear equilibria and periodic solutions, in well-resolved Navier-Stokes flows. This review describes some fundamental and practical aspects of dynamical systems theory for the investigation of turbulence, focusing on recently found invariant solutions and their significance for the dynamical and statistical characterization of low-Reynolds-number turbulent flows. It is shown that the near-wall regeneration cycle of coherent structures can be reproduced by such solutions. The typical similarity laws of turbulence, i.e., the Prandtl wall law and the Kolmogorov law for the viscous range, as well as the pattern and intensity of turbulence-driven secondary flow in a square duct can also be represented by these simple invariant solutions. Source

Takada S.,Osaka University
PLoS ONE | Year: 2013

Arabidopsis thaliana MERISTEM LAYER 1 (ATML1), an HD-ZIP class IV homeobox gene, is one of the key regulators promoting epidermal cell differentiation in Arabidopsis thaliana. We recently showed that ATML1 was able to confer an ectopic shoot epidermis cell fate to non-epidermal tissues of seedlings, suggesting that ATML1 is a master regulator of epidermal cell fate. To further assess the roles of ATML1 and its homologs in epidermal cell differentiation, I generated transgenic plants expressing ATML1 fused with a transcriptional repressor sequence (ATML1-SRDX). Estradiol-induced expression of ATML1-SRDX in the seedlings decreased transcript levels of several epidermis-related genes. Moreover, these transgenic plants exhibited phenotypes such as increased permeability to a hydrophilic dye and fusion of leaves and cotyledons, which are reminiscent of epidermis and/or cuticle-deficient mutants. Epidermal cell morphology was severely affected in the strong lines: filamentous protrusions were formed on the surface of the cotyledons. Marker gene analyses showed that these protrusions did not have epidermis, mesophyll, root hair, or trichome cell identity, suggesting that post-embryonic expression of ATML1-SRDX was sufficient to alter cell identity in pre-existing protodermal cells of the cotyledons. Taken together, these results suggest that ATML1 and/or its target genes are not only necessary for the initial specification of epidermal cell fate but also may be necessary for the maintenance of epidermal cells in later stages. © 2013 Shinobu Takada. Source

Nakayama H.,Osaka University | Otsu K.,Kings College London
Trends in Endocrinology and Metabolism | Year: 2013

Recently, growing evidence suggests that cardiac inflammation contributes to progression of heart failure (HF). However, the precise mechanism has been elusive. Autophagy is well-known phenomenon which plays essential roles in the maintenance of cardiomyocyte homeostasis by clearing damaged proteins and organelles, and dysfunction of this system evokes HF. Although emerging roles of mitochondria in inflammasome development are highlighted in immune cells, an involvement in the heart has not been defined until recently. This review discusses recent advances in understanding the complex mechanisms underlying cardiac inflammation: these studies have revealed that a combination of mitochondrial autophagy and innate immune responses to mitochondrial DNA during increased hemodynamic stress contribute to cardiac inflammation. © 2013 Elsevier Ltd. Source

Toyoda M.,Osaka University
European Journal of Mass Spectrometry | Year: 2010

The mass resolution of a time-of-flight (ToF) mass spectrometer is directly proportional to its total flight path length. We have developed multi-turn ToF mass spectrometers, where ions are stored in a fixed orbit within electrostatic sectors and allowed to propagate the said orbit numerous times. With each successive orbit, the flight path is correspondingly increasing. The first multi-turn ToF mass spectrometer, the MULTUM Linear plus, was developed for cometary exploration. The spectrometer consists of four cylindrical electrostatic sectors and 28 electrostatic quadrupole lenses. The size of the analyzer is 40 cm square. Mass resolution is demonstrated to increase according to the number of ion cycles. A mass resolution of greater than 350,000 was achieved after 501.5 cycles. Another multi-turn ToF mass spectrometer, the MULTUM II, which consists of only four toroidal electrostatic sectors, was also developed in an effort to reduce the number of quadrupole lenses. We are developing various types of mass spectrometer based on the MULTUM II technology, a ToF/ToF mass spectrometer "MULTUM-TOF/TOF", a stigmatic imaging mass spectrometer "MULTUM-IMG" and miniature mass spectrometers of high mass resolving power, the "MULTUM-S" series. © IM Publications LLP 2010. Source

Yamanaka N.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We calculate the two-loop level electric and chromoelectric dipole moments of the fermion involving the fermion-sfermion inner loop, gaugino, and Higgsino in the minimal supersymmetric standard model, and analyze the chromoelectric dipole moment with the top-stop inner loop. It is found that this contribution is comparable with, and even dominates, in some situations over the Barr-Zee type diagram generated from the CP violation of the top squark sector in TeV scale supersymmetry breaking. © 2013 American Physical Society. Source

Matsumoto M.,Osaka University
Optics Express | Year: 2010

An all-optical regeneration scheme for DQPSK signals is proposed and analyzed. In the regenerator, an incoming DQPSK signal is demodulated to two parallel OOK signals by one-symbol delay interferometers. After the amplitude noise is removed by 2R (reamplifying and reshaping) regenerators and the power levels are suitably amplified, the OOK signals modulate the phase of clocked probe pulses in the subsequent all-optical phase modulators by which the noise-reduced (D)QPSK signal is generated. The alteration of phase data encoded on the pulses in the regeneration process can be undone by suitable encoding or decoding. Numerical simulation for short-pulse RZ-DQPSK signals at 160 Gbit/s (80 Gsymbol/s) shows that reduction in both phase and amplitude noise can be obtained by the regeneration scheme where fiber-based 2R amplitude regenerators and phase modulators using self- and cross-phase modulation, respectively, are employed. © 2009 Optical Society of America. Source

Ando Y.,Osaka University | Fu L.,Massachusetts Institute of Technology
Annual Review of Condensed Matter Physics | Year: 2015

In this review, we discuss recent progress in the explorations of topological materials beyond topological insulators; specifically, we focus on topological crystalline insulators and bulk topological erconductors. The basic concepts, model Hamiltonians, and novel electronic properties of these new topological materials are explained. The key role of the symmetries that underlie their topological properties is elucidated. Key issues in their materials realizations are also discussed. © 2015 by Annual Reviews. Source

Lamb C.A.,Cancer Research UK Research Institute | Yoshimori T.,Osaka University | Tooze S.A.,Cancer Research UK Research Institute
Nature Reviews Molecular Cell Biology | Year: 2013

Healthy cells use autophagy as a general 'housekeeping' mechanism and to survive stress, including stress induced by nutrient deprivation. Autophagy is initiated at the isolation membrane (originally termed the phagophore), and the coordinated action of ATG (autophagy-related) proteins results in the expansion of this membrane to form the autophagosome. Although the biogenesis of the isolation membrane and the autophagosome is complex and incompletely understood, insight has been gained into the molecular processes involved in initiating the isolation membrane, the source from which this originates (for example, it was recently proposed that the isolation membrane forms from the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM)) and the role of ATG proteins and the vesicular trafficking machinery in autophagosome formation. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Conspectus Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H• or e-/H+ transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies.In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex.Reactivity of a mononuclear copper(II)-alkylperoxide complex has also been examined to get insights into the intrinsic reactivity of copper(II)-peroxide species, which is usually considered as a sluggish oxidant or just a precursor of copper-oxyl radical type reactive species. However, our studies have unambiguously demonstrated that copper(II)-alkylperoxide complex can be a direct oxidant for C-H bond activation of organic substrates, when the C-H bond activation is coupled with O-O bond cleavage (concerted mechanism). The reactivity studies of these mononuclear copper(II) active-oxygen species (superoxide and alkylperoxide) will provide significantly important insights into the catalytic mechanism of copper monooxygenases as well as copper-catalyzed oxidation reactions in synthetic organic chemistry. © 2015 American Chemical Society. Source

Fukuzumi S.,Osaka University
Dalton Transactions | Year: 2015

High-valent metal-oxo complexes are produced by reductive activation of dioxygen via reduction of metal complexes with reductants and dioxygen. Photoinduced electron transfer from substrates to metal complexes with dioxygen also leads to the generation of high-valent metal-oxo complexes that can oxygenate substrates. In such a case metal complexes act as a photocatalyst to oxygenate substrates with dioxygen. High-valent metal-oxo complexes are also produced by proton-coupled electron-transfer oxidation of metal complexes by one-electron oxidants with water, oxygenating substrates to regenerate metal complexes. In such a case metal complexes act as a catalyst for electron-transfer oxygenation of substrates by one-electron oxidants with water that acts as an oxygen source. The one-electron oxidants which can oxidize metal complexes can be replaced by much weaker oxidants by a combination of redox photocatalysts and metal complexes. Thus, photocatalytic oxygenation of substrates proceeds via photoinduced electron transfer from a photocatalyst to reductants followed by proton-coupled electron transfer oxidation of metal complexes with the oxidized photocatalyst to produce high-valent metal-oxo complexes that oxygenate substrates. Thermal and photoinduced electron-transfer catalytic reactions of high-valent metal-oxo complexes for oxygenation of substrates using water or dioxygen as an oxygen source are summarized in this perspective. © 2015 The Royal Society of Chemistry. Source

The Wilms’ tumor gene WT1 is overexpressed in leukemia and solid tumors and has an oncogenic role in leukemogenesis and tumorigenesis. However, precise regulatory mechanisms of WT1 overexpression remain undetermined. In the present study, microRNA-125a (miR-125a) was identified as a miRNA that suppressed WT1 expression via binding to the WT1-3’UTR. MiR-125a knockout mice overexpressed WT1, developed myeloproliferative disorder (MPD) characterized by expansion of myeloid cells in bone marrow (BM), spleen and peripheral blood, and displayed urogenital abnormalities. Silencing of WT1 expression in hematopoietic stem/progenitor cells of miR-125a knockout MPD mice by short-hairpin RNA inhibited myeloid colony formation in vitro. Furthermore, the incidence and severity of MPD were lower in miR-125a (−/−) mice than in miR-125a (+/−) mice, indicating the operation of compensatory mechanisms for the complete loss of miR-125a. To elucidate the compensatory mechanisms, miRNA array was performed. MiR-486 was occasionally induced in compete loss of miR-125a and inhibited WT1 expression instead of miR-125a, resulting in the cancellation of MPD occurrence. These results showed for the first time the post-transcriptional regulatory mechanisms of WT1 by both miR-125a and miR-486 and should contribute to the elucidation of mechanisms of normal hematopoiesis and kidney development.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.154. © 2015 Macmillan Publishers Limited Source

Sato-Akaba H.,Osaka University
Solid State Nuclear Magnetic Resonance | Year: 2014

A low impedance transceiver circuit consisting of a transmit-receive switch circuit, a class-D amplifier and a transimpedance amplifier (TIA) was newly designed and tested for a nitrogen-14 NQR. An NQR signal at 1.37 MHz from imidazole was successfully observed with the dead time of ~85 μs under the high Q transmission (Q~120) and reception (Q~140). The noise performance of the low impedance TIA with an NQR probe was comparable with a commercial low noise 50 Ω amplifier (voltage input noise: 0.25 nV/Hz) which was also connected to the probe. The protection voltage for the pre-amplifier using the low impedance transceiver was ~10 times smaller than that for the pre-amplifier using a 50 Ω conventional transceiver, which is suitable for NQR remote sensing applications. © 2014 Elsevier Inc. All rights reserved. Source

Recent research has revealed some factors that contribute to cyberbullying, but the role of online disinhibition remains an area for further clarification. This study examined online disinhibition and cyberbullying behavior among Japanese adolescents. A sample of 887 high school students (mean age 16.31) were administered a survey about their cyberbullying experience. The questionnaire included the Online Disinhibition Scale (ODS), a new 11 item instrument developed to assess online disinhibition levels. In order to validate ODS, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted. EFA yielded two factors subsequently named "benign disinhibition" and "toxic disinhibition". Results from CFA supported the two factor solution as an acceptable model fit. Logistic regression analyses showed that online disinhibition was significantly associated with cyberbullying. © 2014 Elsevier Ltd. All rights reserved. Source

Rendle S.,Osaka University
Proceedings - IEEE International Conference on Data Mining, ICDM | Year: 2010

In this paper, we introduce Factorization Machines (FM) which are a new model class that combines the advantages of Support Vector Machines (SVM) with factorization models. Like SVMs, FMs are a general predictor working with any real valued feature vector. In contrast to SVMs, FMs model all interactions between variables using factorized parameters. Thus they are able to estimate interactions even in problems with huge sparsity (like recommender systems) where SVMs fail. We show that the model equation of FMs can be calculated in linear time and thus FMs can be optimized directly. So unlike nonlinear SVMs, a transformation in the dual form is not necessary and the model parameters can be estimated directly without the need of any support vector in the solution. We show the relationship to SVMs and the advantages of FMs for parameter estimation in sparse settings. On the other hand there are many different factorization models like matrix factorization, parallel factor analysis or specialized models like SVD++, PITF or FPMC. The drawback of these models is that they are not applicable for general prediction tasks but work only with special input data. Furthermore their model equations and optimization algorithms are derived individually for each task. We show that FMs can mimic these models just by specifying the input data (i.e. the feature vectors). This makes FMs easily applicable even for users without expert knowledge in factorization models. © 2010 IEEE. Source

Kozawa T.,Osaka University
Journal of Photopolymer Science and Technology | Year: 2013

The stochastic effect is the most serious concern in the development of high resolution lithography with high throughput. Line edge roughness (LER) is a typical phenomena caused by the stochastic effects in the resist pattern formation. In this study, the effects of the initial dispersion of protected units on LER were investigated by a Monte Carlo method on the basis of sensitization and reaction mechanisms of chemically amplified extreme ultraviolet (EUV) resists. The average number of protected units connected to a polymer before acid catalytic reaction was assumed to be 10. When the standard deviation of protected unit distribution (the distribution of the number of protected units connected to a polymer) was changed from 0 to 3, the standard deviation after the acid catalytic chain reaction was increased from 2.3 to 2.9. This increase in the standard deviation was estimated to correspond to 30% increase in LER. Although the reduction of initial standard deviation is somewhat required for the reduction of LER, it was found that the initial standard deviation of approximately 1 is sufficient. © 2013SPST. Source

Azukizawa H.,Osaka University
Journal of Dermatology | Year: 2011

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe acute exfoliative skin diseases developing extensive epidermal detachment and mucosal damage. Although SJS and TEN are mostly caused by drugs, an animal model of TEN using drugs has not been established yet. We have established an autoimmune skin disease model mouse reproducing the devastating skin damage of TEN by a combination of transgenic mice expressing an epidermal model antigen and its specific CD8+ T-cell receptor. In this model mouse, we found that the thymus-derived CD4+CD25+ regulatory T cell (Treg) is a critical regulator of cytotoxic T lymphocytes (CTL) causing TEN. Indeed, loss of Treg function was recently demonstrated by human studies of TEN patients. Although how drug-reactive CTL is activated in vivo is still unknown, this model elucidated the immunological pathomechanism of TEN after CTL obtained cytotoxicity against epidermal keratinocyte. In this review, roles of CTL, Treg, cytotoxic granules and antigen-presenting cells were discussed on pathogenesis of TEN. © 2011 Japanese Dermatological Association. Source

RATIONALE:: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. OBJECTIVE:: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. METHODS AND RESULTS:: We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6 (ATF6), in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of ATF6, including X-box binding protein 1 (XBP1). The decreased levels of XBP1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein (GRP) 78, which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane-resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of GRP78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. CONCLUSIONS:: Doxorubicin activated the ER stress-initiated apoptotic response without inducing the ER chaperone GRP78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of GRP78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment. © 2016 American Heart Association, Inc. Source

Koide Y.,Osaka University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

Spectroscopy of family gauge bosons is investigated based on a U(3) family gauge boson model proposed by Sumino. In his model, the family gauge bosons are in mass eigenstates in a diagonal basis of the charged lepton mass matrix. Therefore, the family numbers are defined by (e1, e2, e3) = (e, μ, τ), while the assignment for quark sector are free. For possible family-number assignments (q1, q2, q3), under a constraint from K0-Kf0 mixing, we investigate possibilities of new physics, e.g. production of the lightest family gauge boson at the LHC, μ -N→e -N, rare K and B decays, and so on. © 2014 The Author. Source

Nishida M.,Osaka University
Journal of High Energy Physics | Year: 2014

Abstract: We consider a holographic model with a scalar field, a tensor field and a direct coupling between them as a superconductor with an s-wave and a d-wave. We find a rich phase structure in the model. The model exhibits a phase of coexistence of the s-wave and the d-wave, or a phase of an order competition. Furthermore, it has a triple point. © 2014, The Author(s). Source

Ejiri H.,Osaka University | Ejiri H.,Czech Technical University | Soukouti N.,University of Jyvaskyla | Suhonen J.,University of Jyvaskyla
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

Spin-dipole (SD) nuclear matrix elements (NMEs) M±(SD2) for unique first forbidden β±2-→0+ ground-state-to-ground-state transitions are studied by using effective microscopic two-nucleon interactions in realistic single-particle model spaces. The observed values of the NMEs Mexp±(SD2) are compared with the values of the single-quasiparticle NMEs Mqp±(SD2) without nucleon spin-isospin (στ) correlation and the QRPA NMEs MQRPA±(SD2) with the στ correlation. The observed SD matrix elements are found to be reduced by the factor k≈0.2 with respect to Mqp±(SD2) and by the factor kNM≈0.5 with respect to MQRPA±(SD2). We then infer that the SD NME is reduced considerably partly by the nucleon στ correlations and partly by other non-nucleonic and nucleonic correlations which are not explicitly included in the QRPA. Impact of the found reduction factors on the magnitudes of the NMEs involved in neutrino-less double beta decays and astro-neutrino interactions are discussed. © 2013 The Authors. Source

Hamada Y.,Kyoto University | Kawai H.,Kyoto University | Oda K.-Y.,Osaka University | Park S.C.,Sungkyunkwan University
Physical Review Letters | Year: 2014

The observed value of the Higgs boson mass indicates that the Higgs potential becomes small and flat at the scale around 1017GeV. Having this fact in mind, we reconsider the Higgs inflation scenario proposed by Bezrukov and Shaposhnikov. It turns out that the nonminimal coupling ξ of the Higgs squared to the Ricci scalar can be smaller than 10. For example, ξ=7 corresponds to the tensor-to-scalar ratio r≃0.2, which is consistent with the recent observation by BICEP2. © 2014 American Physical Society. Source

Hagihira S.,Osaka University
British Journal of Anaesthesia | Year: 2015

The use of EEG monitors to assess the level of hypnosis during anaesthesia has become widespread. Anaesthetists, however, do not usually observe the raw EEG data: they generally pay attention only to the Bispectral Index (BIS) and other indices calculated by EEG monitors. This abstracted information only partially characterizes EEG features. To properly appreciate the availability and reliability of EEG-derived indices, it is necessary to understand how raw EEG changes during anaesthesia. With hemi-frontal lead EEGs obtained under volatile anaesthesia or propofol anaesthesia, the dominant EEG frequency decreases and the amplitude increases with increasing concentrations of anaesthetic. Looking more closely, the EEG changes aremore complicated. At surgical concentrations of anaesthesia, spindle waves (alpha range) become dominant. At deeper levels, this activity decreases, and theta and deltawaves predominate. At even deeper levels, EEG waveformchanges into a burst and suppression pattern, and finally becomes flat. EEG waveforms vary in the presence of noxious stimuli (surgical skin incision), which is not always reflected in BIS, or other processed EEG indices. Spindle waves are adequately sensitive, however, to noxious stimuli: under surgical anaesthesia they disappear when noxious stimuli are applied, and reappearwhen adequate analgesia is obtained. To prevent awareness during anaesthesia, I speculate that themost effective strategy is to administer anaesthetic agents in such a way as to maintain anaesthesia at a level where spindle waves predominate. © 2015 The Author Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. Source

Arnaud B.,Rennes Institute of Physics | Giret Y.,Osaka University | Giret Y.,University College London
Physical Review Letters | Year: 2013

By means of first principles calculations, we compute the effective electron-phonon coupling constant G0 governing the electron cooling in photoexcited bismuth. G0 strongly increases as a function of electron temperature, which can be traced back to the semimetallic nature of bismuth. We also use a thermodynamical model to compute the time evolution of both electron and lattice temperatures following laser excitation. Thereby, we simulate the time evolution of (1 -1 0), (-2 1 1) and (2 -2 0) Bragg peak intensities measured by Sciaini et al. in femtosecond electron diffraction experiments. The effect of the electron temperature on the Debye-Waller factors through the softening of all optical modes across the whole Brillouin zone turns out to be crucial to reproduce the time evolution of these Bragg peak intensities. © 2013 American Physical Society. Source

Ohkubo S.,Osaka University | Hirabayashi Y.,Hokkaido University
Physical Review C - Nuclear Physics | Year: 2014

We present evidence for the nuclear ripples superimposed on the Airy structure of the nuclear rainbow, which is similar to the meteorological rainbow. The mechanism of the nuclear ripples is also similar to that of the meteorological rainbow, which is caused by the interference between the externally reflective waves and refractive waves. The nuclear ripple structure was confirmed by analyzing the elastic angular distribution in O16+C12 rainbow scattering at EL=115.9 MeV using the coupled channels method by taking account of coupling to the excited states of C12 and O16 with a double folding model derived from a density-dependent effective nucleon-nucleon force with realistic wave functions for C12 and O16. The coupling to the excited states plays the role of creating the external reflection. © 2014 American Physical Society. Source

Koide Y.,Osaka University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

On the basis of a supersymmetric yukawaon model, Sumino's relation for charged lepton masses is re-derived. A relation between values of K (μ) ≡ (me + mμ + mτ) / (sqrt(me) + sqrt(mμ) + sqrt(mτ))2 and κ (μ) ≡ sqrt(me mμ mτ) / (sqrt(me) + sqrt(mμ) + sqrt(mτ))3 is investigated without using the relation K = 2 / 3. Predicted value of κ (μ) is compared with the observed value of κ (μ), and it is concluded that the value ξ (μ) ≡ (3 / 2) K (μ) - 1 is of the order of 10- 3 or less. © 2010 Elsevier B.V. All rights reserved. Source

Asada M.,Osaka University
Neuroscience Research | Year: 2015

We have been advocating cognitive developmental robotics to obtain new insight into the development of human cognitive functions by utilizing synthetic and constructive approaches. Among the different emotional functions, empathy is difficult to model, but essential for robots to be social agents in our society. In my previous review on artificial empathy (. Asada, 2014b), I proposed a conceptual model for empathy development beginning with emotional contagion to envy/schadenfreude along with self/other differentiation. In this article, the focus is on two aspects of this developmental process, emotional contagion in relation to motor mimicry, and cognitive/affective aspects of the empathy. It begins with a summary of the previous review (. Asada, 2014b) and an introduction to affective developmental robotics as a part of cognitive developmental robotics focusing on the affective aspects. This is followed by a review and discussion on several approaches for two focused aspects of affective developmental robotics. Finally, future issues involved in the development of a more authentic form of artificial empathy are discussed. © 2014 The Authors. Source

Wakamatsu M.,Osaka University
European Physical Journal A | Year: 2010

The orbital angular momenta Lu and Ld of up- and down-quarks in the proton are estimated as functions of the energy scale as model independently as possible on the basis of Ji's angular-momentum sum rule. This analysis indicates that Lu - Ld is large and negative even at the low energy scale of nonperturbative QCD, in contrast to Thomas' similar analysis based on the refined cloudy bag model. We pursuit the origin of this apparent discrepancy and suggest that it may have a connection with the fundamental question of how to define quark orbital angular momenta in QCD. © 2010 SIF, Springer-Verlag Berlin Heidelberg. Source

Nagatsuma T.,Osaka University
IEICE Electronics Express | Year: 2011

A number of technical breakthroughs in electronics and photonics made since the early 1990s have started to bring terahertz (THz)-wave technologies from laboratory demonstrators to industrial applications such as non-destructive testing, security, medicine, communications, etc. This paper overviews the latest progress in THz-wave technologies in terms of components such as sources and detectors, and system applications, and discusses future challenges towards market developments. © IEICE 2011. Source

Kawamura H.,Osaka University
Journal of Physics Condensed Matter | Year: 2011

Ordering properties of XY-like spin-glass magnets with an easy-plane magnetic anisotropy are studied based on a symmetry consideration and the results of recent numerical simulations on the pure Heisenberg and XY spin-glass models. The effects of an easy-plane-type uniaxial anisotropy, a random magnetic anisotropy and an applied magnetic field are investigated. In the XY regime in zero field, the 'spin-chirality decoupling' persists even under the random magnetic anisotropy, escaping the 'spin-chirality recoupling' phenomenon which inevitably occurs in the Heisenberg regime. Contrast between the scalar chiral order and the vector chiral order is emphasized. Implications for experiments are discussed. © 2011 IOP Publishing Ltd. Source

Nagatsuma T.,Osaka University
Journal of Infrared, Millimeter, and Terahertz Waves | Year: 2011

The increasing demand of unoccupied and unregulated bandwidth for wireless communication systems will inevitably lead to the extension of operation frequencies toward the lower THz frequency range. Higher carrier frequencies will allow for fast transmission of huge amounts of data as needed for new emerging applications. Despite the tremendous hurdles that have to be overcome with regard to sources and detectors, circuit and antenna technology and system architecture to realize ultrafast data transmission in a scenario with extensive transmission loss, a new area of research is beginning to form. In this article we give an overview of emerging technologies and system research that might lead to ubiquitous THz communication systems in the future. © Springer Science+Business Media, LLC 2011. Source

Okamura Y.,Osaka University | Dixon J.E.,University of California at San Diego
Physiology | Year: 2011

Voltage-sensing phosphoinositide phosphatase (VSP) contains voltage sensor and cytoplasmic phosphatase domains. A unique feature of this protein is that depolarization-induced motions of the voltage sensor activate PtdIns(3,4,5)P3 and PtdIns(4,5)P2 phosphatase activities. VSP exhibits remarkable structural similarities with PTEN, the phosphatase and tensin homolog deleted on chromosome 10. These similarities include the cytoplasmic phosphatase region, the phosphoinositide binding region, and the putative membrane interacting C2 domain.© 2011 by the American Physiological Society. Source

The ubiquitin conjugation system regulates a wide variety of biological phenomena including protein degradation and signal transduction by regulating protein function via polyubiquitin conjugation in most cases. Several types of polyubiquitin chains exist in cells, and the type of polyubiquitin chain conjugated to a protein seems to determine how that protein is regulated. We identified a novel linear polyubiquitin chain and the ubiquitin-protein ligase complex that assembles it, designated LUBAC. Both were shown to have crucial roles in the canonical NFκB activation pathway. This year, three groups, including our laboratory, identified SHARPIN as a new subunit of LUBAC. Of great interest, Sharpin was identified as a causative gene of chronic proliferative dermatitis in mice (cpdm), which are characterized by numerous inflammatory symptoms including chronic dermatitis, arthritis and immune disorders. Deletion of SHARPIN drastically reduces the amount of LUBAC and attenuates signal-induced NFκB activation. The pleomorphic symptoms of cpdm mice suggest that LUBAC-mediated NFκB activation may play critical roles in mammals and be involved in various disorders. A forward look into the linear polyubiquitin research is also discussed. © 2011 Landes Bioscience. Source

Stasevich T.J.,Osaka University | McNally J.G.,U.S. National Institutes of Health
Chromosoma | Year: 2011

The assembly of the transcription machinery is a key step in gene activation, but even basic details of this process remain unclear. Here we discuss the apparent discrepancy between the classic sequential assembly model based mostly on biochemistry and an emerging dynamic assembly model based mostly on fluorescence microscopy. The former model favors a stable transcription complex with subunits that cooperatively assemble in order, whereas the latter model favors an unstable complex with subunits that may assemble more randomly. To confront this apparent discrepancy, we review the merits and drawbacks of the different experimental approaches and list potential biasing factors that could be responsible for the different interpretations of assembly. We then discuss how these biases might be overcome in the future with improved experiments or new techniques. Finally, we discuss how kinetic models for assembly may help resolve the ordered and stable vs. random and dynamic assembly debate. © 2011 Springer-Verlag (outside the USA). Source

Kanki T.,Kyushu University | Klionsky D.J.,University of Michigan | Okamoto K.,Osaka University
Antioxidants and Redox Signaling | Year: 2011

The mitochondrion is an organelle that carries out a number of important metabolic processes such as fatty acid oxidation, the citric acid cycle, and oxidative phosphorylation. However, this multitasking organelle also generates reactive oxygen species (ROS), which can cause oxidative stress resulting in self-damage. This type of mitochondrial damage can lead to the further production of ROS and a resulting downward spiral with regard to mitochondrial capability. This is extremely problematic because the accumulation of dysfunctional mitochondria is related to aging, cancer, and neurodegenerative diseases. Accordingly, appropriate quality control of this organelle is important to maintain proper cellular homeostasis. It has been thought that selective mitochondria autophagy (mitophagy) contributes to the maintenance of mitochondrial quality by eliminating damaged or excess mitochondria, although little is known about the mechanism. Recent studies in yeast identified several mitophagy-related proteins, which have been characterized with regard to their function and regulation. In this article, we review recent advances in the physiology and molecular mechanism of mitophagy and discuss the similarities and differences of this degradation process between yeast and mammalian cells. © 2011 Mary Ann Liebert, Inc. Source

Kobashi J.,Osaka University
Nature Photonics | Year: 2016

Reflective metasurfaces based on metallic and dielectric nanoscatterers have attracted interest owing to their ability to control the phase of light. However, because such nanoscatterers require subwavelength features, the fabrication of elements that operate in the visible range is challenging. Here, we show that chiral liquid crystals with a self-organized helical structure enable metasurface-like, non-specular reflection in the visible region. The phase of light that is Bragg-reflected off the helical structure can be controlled over 0–2π depending on the spatial phase of the helical structure; thus planar elements with arbitrary reflected wavefronts can be created via orientation control. The circular polarization selectivity and external field tunability of Bragg reflection open a wide variety of potential applications for this family of functional devices, from optical isolators to wearable displays. © 2016 Nature Publishing Group Source

Kozawa T.,Osaka University
Japanese Journal of Applied Physics | Year: 2012

The stochastic effect of incident photons is a significant concern in nanometer-scale fabrication using highly sensitive resists because the fluctuation of the line edges of resist patterns should be suppressed to guarantee normal operation of fabricated devices. However, what matters the most in the line edge roughness (LER) formation is not photon fluctuation but protected unit fluctuation. In this study, the changes in the stochastic effect of acid catalytic chain reaction were investigated using the Monte Carlo method. It was theoretically confirmed that the reason why LER decreases with the increase in exposure dose and/or acid generator concentration is not the reduction of the fluctuations of concentrations of photons (shot noise), acids, or protected units but the increase in chemical gradient. © 2012 The Japan Society of Applied Physics. Source

Nakagami H.,Osaka University
Diabetes and Metabolism Journal | Year: 2013

Obesity gives vent to many diseases such as type 2 diabetes, hypertension, and hyperlipidemia, being considered as the main causes of mortality and morbidity worldwide. The pathogenesis and pathophysiology of metabolic syndrome can well be understood by studying the molecular mechanisms that control the development and function of adipose tissue. In human body, exist two types of adipose tissue, the white and the brown one, which are reported to play various roles in energy homeostasis. The major and most efficient storage of energy occurs in the form of triglycerides in white adipose tissue while brown adipose tissue actively participates in both basal and inducible energy consumption in the form of thermogenesis. Recent years have observed a rapid and greater interest towards developmental plasticity and therapeutic potential of stromal cells those isolated from adipose tissue. The adipocyte differentiation involves a couple of regulators in the white or brown adipogenesis. Peroxisome proliferators- activated receptor- γ actively participates in regulating carbohydrate and lipid metabolism, and also acts as main regulator of both white and brown adipogenesis. This review based on our recent research, seeks to highlight the adipocyte differentiation. © 2013 Korean Diabetes Association. Source

Nakano M.,Osaka University | Oshio H.,University of Tsukuba
Chemical Society Reviews | Year: 2011

The study of the magnetic properties of highly anisotropic paramagnetic molecules is an area of intense current research interest. Of these, single-molecule magnets (SMMs) and single-chain magnets (SCMs) showing non-equilibrium magnetization have remained a key topic over the past two decades. The slow magnetization reversals found in SMMs and SCMs are contingent on two requirements: a large ground-state spin forbidding direct quantum transitions of spin reversal, and a series of excited spin levels, due to the anisotropy of the system, which can act as steppingstones for the thermal relaxation of the spin orientations (the Orbach process). In this critical review, the latter requirement, i.e. the existence of magnetic anisotropies in paramagnetic species, is reviewed with the aim of providing clues towards the rational design of molecule-based magnets (100 references). © The Royal Society of Chemistry 2011. Source

Intestinal motility disorders are a major cause of intestinal failure. Severe cases such as idiopathic pseudo-obstruction represent life-threatening illnessed. Intestinal transplantation is a treatment for severe motility disorders with irreversible intestinal failure. However, the prevalence of severe motility disorders is unknown. We performed a national survey to identify patients with intestinal motility disorders who require an intestinal transplant. The national survey of 302 institutions treating intestinal motility disorders identified 147 patients treated from 2006 to 2011 at 46 institutions. The mean patient age was 12.1 years (range, 0.3-77.5). The mean age of onset was 3.0 years (range, 0.0-68.8). Diagnoses included chronic idiopathic intestinal pseudo-obstruction (n = 96), Hirschsprung disease (n = 29), megacystis microcolon intestinal hypoperistalsis syndrome (n = 18), and other (n = 6). There were 126 survivors and 21 patients who died during the last 5 years. The mortality rate was 14.3%. Eighty-five percent of patients required parenteral nutrition for more than 6 months, which was defined as irreversible intestinal failure. Among surviving patients with irreversible intestinal failure, 8 (9.4 %) developed hepatic failure with jaundice and 27 (31.8%) 2 or more central vein thromboses. In all, at least 35 patients (41%) with irreversible failure due to intestinal motility disorders may be candidates for transplantation. The prevalence of severe intestinal motility disorders was elucidated in Japan. Severe cases should be referred to transplant centers. Copyright © 2013 Elsevier Inc. All rights reserved. Source

Line edge roughness (LER) has been the most serious problem in the development of high-resolution lithography for manufacturing semiconductor devices. LER is caused by the stochastic effects in resist pattern formation. In this study, the effects of the molecular weight and protection ratio of a resist backbone polymer on latent image fluctuation were investigated by a Monte Carlo method. From the viewpoint of latent image fluctuation, a high molecular weight and a high protection ratio were found to be favorable for the reduction in LER. © 2012 The Japan Society of Applied Physics. Source

Tanizawa K.,Osaka University
Journal of Biochemistry | Year: 2011

Hydrogen sulfide (H2S) has been established as the third gaseous signaling molecule following nitric oxide and carbon monoxide and participates in a variety of cellular functions such as modulation of neuronal transmission, endothelium-dependent vasorelaxation, stimulation of angiogenesis and regulation of insulin release. Although cystathionine β-synthase and cystathionine γ-lyase have been regarded as the main producers of H2S in many tissues including brain, liver and kidney, Kimura and his colleagues have recently communicated that 3-mercaptopyruvate sulphurtransferase coupled with cysteine (aspartate) aminotransferase is responsible for the production of H2S in the vascular endothelium of the thoracic aorta [Shibuya et al. (2009) J. Biochem. 146, 623-626]. This finding provides a new insight into the production of the physiologically important signaling molecule. © 2011 The Authors. Source

Mayanagi T.,Osaka University | Sobue K.,Iwate Medical University
Cell Adhesion and Migration | Year: 2011

The actin cytoskeleton plays a key role in regulating cell motility. Caldesmon (CaD) is an actin-linked regulatory protein found in smooth muscle and non-muscle cells that is conserved among a variety of vertebrates. It binds and stabilizes actin filaments, as well as regulating actin-myosin interaction in a calcium (Ca2+)/calmodulin (CaM)- and/or phosphorylation-dependent manner. CaD function is regulated qualitatively by Ca2+/CaM and by its phosphorylation state and quantitatively at the mRN A level, by three different transcriptional regulation of the CALD1 gene. CaD has numerous functions in cell motility, such as migration, invasion and proliferation, exerted via the reorganization of the actin cytoskeleton. Here we will outline recent findings regarding CaD's structural features and functions. © 2011 Landes Bioscience. Source

Matsuda M.,Institute of Clinical Research | Shimomura I.,Osaka University
Reviews in Endocrine and Metabolic Disorders | Year: 2014

The recent increase in populations with obesity is a worldwide social problem, and the enhanced susceptibility of obese people to metabolic and cardiovascular diseases has become a growing health threat. An understanding of the molecular basis for obesity-associated disease development is required to prevent these diseases. Many studies have revealed that the mechanism involves various bioactive molecules that are released from adipose tissues and designated as adipocytokines/adipokines. Adiponectin is an adipocytokine that exerts insulin-sensitizing effects in the liver and skeletal muscle via adenosine monophosphate-activated protein kinase and proliferator-activated receptor α activation. Additionally, adiponectin can suppress atherosclerosis development in vascular walls via various anti-inflammatory effects. In contrast, oxidative stress is a harmful factor that systemically increases during obesity and promotes the development of diabetes, atherosclerosis, and various other diseases. In obese mice, oxidative stress is enhanced in adipose tissue before diabetes development, but not in the liver, skeletal muscle, and aorta, suggesting that in obesity, adipose tissue may be a major source of reactive oxygen species (ROS). ROS suppress adiponectin production in adipocytes. Treatment of obese mice with anti-oxidative agents improves insulin resistance and restores adiponectin production. Recent studies have demonstrated that adiponectin protects against oxidative stress-induced damage in the vascular endothelium and myocardium. Thus, decreased circulating adiponectin levels and increased oxidative stress, which are closely linked to each other, should be deeply involved in obesity-associated metabolic and cardiovascular disease pathogenesis. © 2013 Springer Science+Business Media. Source

Takano T.,Osaka University
Endocrine Journal | Year: 2014

Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARγ1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells. © The Japan Endocrine Society. Source

Katoh K.,Osaka University | Katoh K.,Japan National Institute of Advanced Industrial Science and Technology | Frith M.C.,Japan National Institute of Advanced Industrial Science and Technology
Bioinformatics | Year: 2012

Two methods to add unaligned sequences into an existing multiple sequence alignment have been implemented as the '-add' and '-addfragments' options in the MAFFT package. The former option is a basic one and applicable only to full-length sequences, whereas the latter option is applicable even when the unaligned sequences are short and fragmentary. These methods internally infer the phylogenetic relationship among the sequences in the existing alignment and the phylogenetic positions of unaligned sequences. Benchmarks based on two independent simulations consistently suggest that the "-addfragments" option outperforms recent methods, PaPaRa and PAGAN, in accuracy for difficult problems and that these three methods appropriately handle easy problems. © The Author 2012. Published by Oxford University Press. All rights reserved. Source

Nakayama T.,Osaka University | Oishi K.,National Institute of Infectious Disease
FEMS Microbiology Letters | Year: 2013

Although studies have reported numerous effects of coffee on human health, few studies have examined its specific effects on gut microbiota. This study aimed to clarify the influence of coffee and galacto-oligosaccharide (GOS) consumption on gut microbiota and host responses. After mice consumed coffee and GOS, their intestines were sampled, and the bacterial counts were measured with quantitative RT-PCR. Results showed that GOS consumption significantly increased total bacteria counts in the proximal colon. Although Escherichia coli and Clostridium spp. counts significantly decreased in the proximal colon, Bifidobacterium spp. counts increased remarkably in the same area. A bacterial growth inhibition assay was also conducted, and the results showed that E. coli growth was inhibited only by a coffee agar. Host responses were also investigated, revealing that coffee and GOS consumption remarkably increased aquaporin8 expression in the proximal colon. In conclusion, coffee has antibiotic effects, and GOS significantly decreased E. coli and Clostridium spp. counts, but increased Bifidobacterium spp. counts remarkably. Aquaporin8 expression was also increased with a mixture of coffee and GOS consumption. This is the first study to demonstrate that coffee consumption can regulate gut microbiota and increase aquaporin8, both of which are necessary for maintaining intestinal balance. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. Source

Okabe M.,Osaka University
Development (Cambridge) | Year: 2013

Fertilization is the process by which eggs and spermatozoa interact, achieve mutual recognition, and fuse to create a zygote, which then develops to form a new individual, thus allowing for the continuity of a species. Despite numerous studies on mammalian fertilization, the molecular mechanisms underpinning the fertilization event remain largely unknown. However, as I summarize here, recent work using both gene-manipulated animals and in vitro studies has begun to elucidate essential sperm and egg molecules and to establish predictive models of successful fertilization. © 2013. Source

Sumiyoshi H.,Kyoto University | Fujimoto S.,Osaka University
Physical Review Letters | Year: 2016

We propose a torsional response raised by a lattice dislocation in Weyl semimetals akin to a chiral magnetic effect; i.e., a fictitious magnetic field arising from a screw or edge dislocation induces a charge current. We demonstrate that, in sharp contrast to the usual chiral magnetic effect that vanishes in real solid state materials, the torsional chiral magnetic effect exists even for realistic lattice models, which implies the experimental detection of the effect via superconducting quantum interference device or nonlocal resistivity measurements in Weyl semimetal materials. © 2016 American Physical Society. Source

The chemical weathering of porous rhyolite from Kozushima, Japan was studied, and the factors controlling the weathering rate, including advection, diffusion and dissolution, were characterized using laboratory experiments. The results were used to analyze the reaction and transport rates, and the relationship between the weathering rates obtained in the laboratory and field was evaluated. A flow-through dissolution experiment using a rhyolite core demonstrated that the dissolution rate R (molcm-2s-1) in deionized water depends on time t (days) according to the relationship R=2.9×10-16t-0.65. The dissolution rate was also dependent on the concentration of dissolved Si according to the relationship R∝(1-Ωn), where Ω=c/ceq (ceq=230μmolL-1) and n=1.0 or 0.33. The hydraulic conductivity and diffusion coefficients were measured under water-saturated and unsaturated conditions. The saturated hydraulic conductivity was 10 times greater than the unsaturated conductivity, and the saturated effective diffusion coefficient of dissolved Si was 5 times greater than the unsaturated diffusion coefficient. Previous studies on the weathering of the rhyolites from Kozushima have shown that the field dissolution rate over 52,000years was 3×10-19-6×10-19molSicm-2s-1. These values are 12-1000 times lower than the dissolution rates obtained in the laboratory over a reaction time of 277days. Reactive transport analysis demonstrated that the effect of Ω on the dissolution rate is enhanced as the water saturation decreases. The rate-decreasing effect of Ω was large in the early stages of weathering and then gradually decreased with time. The 52,000-year weathering period is inferred to have occurred following a decrease in the dissolution rate to a value close to the "field rate" during an early weathering stage and subsequent further decrease in the rate owing to the effect of Ω. © 2013 Elsevier Ltd. Source

The endosomal sorting complexes required for transport (ESCRTs) mediate membrane fission from the cytoplasmic face of the bud neck. ESCRTs were originally identified as factors involved in multivesicular body vesicle biogenesis in yeast but have since been shown to function in other membrane fission events in mammalian cells, including enveloped virus budding and the abscission step of cytokinesis. Several recent studies have revealed that not all ESCRT factors are required for each of these biological processes, and this review summarizes our current understanding of the different requirements for ESCRT factors in these three different ESCRT-mediated mammalian membrane fission processes. The endosomal sorting complexes required for transport (ESCRTs) mediate membrane fission of the bud neck in multivesicular body (MVB) vesicle formation, virus budding, and cytokinesis. Several recent studies have revealed that not all ESCRT factors are required for each biological process. This minireview summarizes our current understanding of the different requirements for ESCRT factors in three different biological processes © 2012 The Author Journal compilation © 2012 FEBS. Source

Vergados J.D.,University of Ioannina | Vergados J.D.,CERN | Ejiri H.,Osaka University | Ejiri H.,Czech Technical University | Simkovic F.,Comenius University
Reports on Progress in Physics | Year: 2012

Neutrinoless double-beta decay, which is a very old and yet elusive process, is reviewed. Its observation will signal that the lepton number is not conserved and that the neutrinos are Majorana particles. More importantly it is our best hope for determining the absolute neutrino-mass scale at the level of a few tens of meV. To achieve the last goal certain hurdles must be overcome involving particle, nuclear and experimental physics. Nuclear physics is important for extracting useful information from the data. One must accurately evaluate the relevant nuclear matrix elements - a formidable task. To this end, we review the sophisticated nuclear structure approaches which have recently been developed, and which give confidence that the required nuclear matrix elements can be reliably calculated employing different methods: (a) the various versions of the quasiparticle random phase approximations, (b) the interacting boson model, (c) the energy density functional method and (d) the large basis interacting shell model. It is encouraging that, for the light neutrino-mass term at least, these vastly different approaches now give comparable results. From an experimental point of view it is challenging, since the life times are long and one has to fight against formidable backgrounds. One needs large isotopically enriched sources and detectors with high-energy resolution, low thresholds and very low background. If a signal is found, it will be a tremendous accomplishment. The real task then, of course, will be the extraction of the neutrino mass from the observations. This is not trivial, since current particle models predict the presence of many mechanisms other than the neutrino mass, which may contribute to or even dominate this process. In particular, we will consider the following processes: The neutrino induced, but neutrino-mass independent contribution. Heavy left and/or right-handed neutrino-mass contributions. Intermediate scalars (doubly charged, etc). Supersymmetric (SUSY) contributions. We will show that it is possible to disentangle the various mechanisms and unambiguously extract the important neutrino-mass scale, if all the signatures of the reaction are searched for in a sufficient number of nuclear isotopes. © 2012 IOP Publishing Ltd. Source

Ngo K.X.,Osaka University
Journal of biotechnology | Year: 2010

The strategy to prepare a novel biocatalyst by the immobilization of chitosanase onto liposome (ICL) was carried out based on the direct interaction of liposomes with cell membrane of Streptomyces griseus cell. The ICL was characterized in relation to the molecular weight of protein, the chitosanase activity, the effect of the surface hydration of various liposomes on hydrolysis activity of immobilized chitosanase and the stability of ICL under various extreme conditions. The SDS-PAGE analysis of the purified ICL sample shows the existence of a protein with approximately 39kDa that corresponded to the sum of weight of the mature chitosanase and its signal peptide (38.8kDa). The above protein of ICL also expresses the chitosanase activity that is significantly higher than that of the conventional chitosanase. Furthermore, the surface hydration of liposomes used to prepare ICL that affected the activity of immobilized chitosanase verified the importance of liposome surfaces. Indeed, the stability of ICL assayed by measuring the chitosanase activity is significantly higher than that of conventional chitosanase under various temperatures and pH conditions. These characteristics of ICL show the possible preparation of the biocatalysts that can be prepared by immobilizing enzymes onto liposome vesicles properly. Source

Chatani N.,Osaka University
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry | Year: 2013

Given that C-H bonds are ubiquitous in organic compounds, substrate functionalization via C-H bond activation appears as a challenging straightforward method in organic synthesis, eliminating the multiple steps and limitations associated with the preparation of functionalized starting materials. Regioselectivity is the important issue to be addressed in the transformation of C-H bonds because organic molecules can have many different types of C-H bonds. The use of a directing group can largely overcome the issue of regio-control by allowing the catalyst to come into close proximity to the targeted C-H bonds which, in most cases, are ortho C-H bonds. A wide variety of functional groups has been evaluated as directing groups to date in the transformation of C-H bonds. The development of new types of directing groups continues to be important, in terms of exploring novel types of transformations of C-H bonds that cannot be achieved by conventional directing groups. In 2005, Daugulis reported the arylation of unactivated C(sp3) -H bonds using 8-aminoquinoline and picolinamide as a N,N-bidentate directing group in conjunction with Pd(OAc)2 as the catalyst. Encouraged by these promising results, a number of transformations of C-H bonds have since been developed using bidentate directing group systems. In this review, a recent advance on chelation-assisted transformation of C-H bonds by taking advantage of a bidentate directing group is described. Source

Ogoshi S.,Osaka University
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry | Year: 2013

Nickelacycles have been known as a key reaction intermediate. The β-hydrogen transfer reactions from nickelacycles allow us to synthesize acyclic organic compounds. The reductive elimination from nickelacycles allows us to synthesize a variety of cyclic organic compounds. Thus, the generation of a new nickelacycles from a new combination of unsaturated compounds and nickel (0) species is a key to develop nickel-catalyzed new reactions. We report here the new molecular transformations of a variety of unsaturated compounds via nickelacycles in which both acyclic and cyclic compounds were obtained. In addition, the isolation of the reaction intermediates and their reaction mechanisms are discussed as well. Source

Ichimori H.,Osaka University
Circulation journal : official journal of the Japanese Circulation Society | Year: 2013

To investigate the possible role of sex hormones in the pathogenesis of pulmonary arterial hypertension (PAH), the effect of β-estradiol (E2) on bone morphogenetic protein (BMP) signaling, a key signaling pathway involved in PAH, was studied in human pulmonary arterial endothelial cells (HPAEC). BMP signaling molecules, including BMP receptor, Smad1/5/8 and Id1, were studied in HPAEC under 1% O2 (hypoxia) and 21% O2 (normoxia) as well as the effect of hypoxia-inducible factor (HIF)-1α expression in the presence of E2 on BMP signaling. The effects of an estrogen receptor (ER) antagonist (ICI 182,780) and cycloheximide, and the interaction of ER with Smad or HIF-1α were also studied. In the presence of E2, BMP signaling was augmented under normoxia but suppressed under hypoxia. HIF-1α accumulation suppressed BMP signaling, whereas HIF-1α inhibition augmented signaling. These effects were cancelled by ICI 182,780. Moreover, binding between ER, HIF-1α and phosphorylated (p)-Smad1/5/8 proteins occurred only under hypoxia. On inhibition of de novo synthesis with cycloheximide, however, p-Smad1/5/8 expression was suppressed only under normoxia. The effects of E2 on BMP signaling in HPAEC altered depending on O2 concentration and different mechanisms may be involved. BMP and sex hormones may play an important role in PAH development. Source

Fukuzumi S.,Osaka University | Fukuzumi S.,Ewha Womans University
Coordination Chemistry Reviews | Year: 2013

Electron-transfer properties of heme and non-heme high-valent metal-oxo complexes are overviewed in relation to their reactivity toward oxidation of substrates. The rate constants of electron transfer from a series of electron donors to various heme and non-heme high-valent metal-oxo complexes such as compound I and compound II of horseradish peroxidase (HRP), (TMP)MnIV(O) ((TMP=tetramesityl-porphyrinate dianion), (TBP8Cz)MnV(O) (TBP8Cz=octa-tert-butylphenylcorrolazinate trianion) and [(L)FeIV(O)]2+, where L=TMC, 1,4,8,11-tetra-methyl-1,4,8,11-tetraazacyclotetradecane; Bn-TPEN, N-benzyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine; N4Py, N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine; bisp, 3,7-diazabicyclo[3.3.1]nonane) were evaluated in light of the Marcus theory of electron transfer in order to determine the reorganization energy (λ) for electron transfer. The λ value increases in the order: 1.3eV (compound I of HRP), 1.53eV [(TBP8Cz)MnV(O)], 1.6eV (compound II of HRP), 1.7eV [(TMP)MnIV(O)], 2.05eV [(bisp)FeIV(O)]2+, 2.37eV [(TMC)FeIV(O)]2+), 2.55eV ([(Bn-TPEN)FeIV(O)]2+), 2.74eV ([(N4Py)FeIV(O)]2+). The λ value of compound I of HRP is the smallest among those of high-valent metal-oxo complexes, because the site of the reduction is on the porphyrin ligand, whereas the site of the reduction is on the metal for the other high-valent metal-oxo complexes. The λ values of high-valent metal-oxo porphyrins are generally smaller than those of non-heme iron(IV)-oxo complexes. The effects of Lewis acidic metal ions and Brønsted acids on the one-electron reduction of high-valent metal-oxo complexes are also overviewed in relation to their enhancement of the oxidizing ability towards reductants. © 2012 Elsevier B.V. Source

Tsubota K.-I.,Chiba University | Wada S.,Osaka University
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

A two-dimensional computer simulation model was proposed for tank-treading and tumbling motions of an elastic biconcave red blood cell (RBC) under steady shear flow. The RBC model consisted of an outer cellular membrane and an inner fluid; the membrane's elastic properties were modeled by springs for stretch/compression and bending to consider the membrane's natural state in a practical manner. Membrane deformation was coupled with incompressible viscous flow of the inner and outer fluids of the RBC using a particle method. The proposed simulation model was capable of reproducing tank-treading and tumbling motions of an RBC along with rotational oscillation, which is the transition between the two motions. In simulations using the same initial RBC shape with different natural states of the RBC membrane, only tank-treading motion was exhibited in the case of a uniform natural state of the membrane, and a nonuniform natural state was necessary to generate the rotational oscillation and tumbling motion. Simulation results corresponded to published data from experimental and computational studies. In the range of simulation parameters considered, the relative membrane elastic force versus fluid viscous force was ∼1 at the transition when the natural state nonuniformity was taken into account in estimating the membrane elastic force. A combination of natural state nonuniformity and elastic spring constant determined that change in the RBC deformation at the transition is that from a large compressive deformation to no deformation, such as rigid body. © 2010 The American Physical Society. Source

Iwami T.,Kyoto University | Kitamura T.,Osaka University | Kiyohara K.,Tokyo Womens Medical University | Kawamura T.,Kyoto University
Circulation | Year: 2015

Background - The best cardiopulmonary resuscitation (CPR) technique for survival after out-of-hospital cardiac arrests (OHCAs) has been intensively discussed in the recent few years. However, most analyses focused on comparison at the individual level. How well the dissemination of bystander-initiated chest compression-only CPR (CCCPR) increases survival after OHCAs at the population level remains unclear. We therefore evaluated the impact of nationwide dissemination of bystander-initiated CCCPR on survival after OHCA. Methods and Results - A nationwide, prospective, population-based, observational study covering the whole population of Japan and involving consecutive OHCA patients with resuscitation attempts was conducted from January 2005 through December 2012. The main outcome measure was 1-month survival with favorable neurological outcome. The incidence of survival with favorable neurological outcome attributed to types of bystander CPR (CCCPR and conventional CPR with rescue breathing) was estimated. Among 816 385 people experiencing OHCAs before emergency medical services arrival, 249 970 (30.6%) received CCCPR, 100 469 (12.3%) received conventional CPR, and 465 946 (57.1%) received no CPR. The proportion of OHCA patients receiving CCCPR or any CPR (either CCCPR or conventional CPR) by bystanders increased from 17.4% to 39.3% (P for trend <0.001) and from 34.6% to 47.3% (P for trend <0.001), respectively. The incidence of survival with favorable neurological outcome attributed to CCCPR per 10 million population significantly increased from 0.6 to 28.3 (P for trend=0.010), and that by any bystander-initiated CPR significantly increased from 9.0 to 43.6 (P for trend=0.003). Conclusion - Nationwide dissemination of CCCPR for lay-rescuers was associated with the increase in the incidence of survival with favorable neurological outcome after OHCAs in Japan. © 2015 American Heart Association, Inc. Source

Onishi M.,Osaka University
Cell death & disease | Year: 2013

Small G proteins of the Rho family are pivotal regulators of several signaling networks. The Ras homolog family (Rho) and one of its targets, Rho-associated protein kinase (ROCK), participate in a wide variety of biological processes, including bone formation. A previous study has demonstrated that the ROCK inhibitor Y-27632 enhanced bone formation induced by recombinant human bone morphogenetic protein-2 (BMP-2) in vivo and in vitro. However, the effect of other Rho family members, such as Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42), on bone formation remains unknown. In this study, we investigated whether Rac1 also participates in BMP-2-induced osteogenesis. Expression of a dominant-negative mutant of Rac1 enhanced BMP-2-induced osteoblastic differentiation in C2C12 cells, whereas a constitutively active mutant of Rac1 attenuated that effect. Knockdown of T-lymphoma invasion and metastasis 1 (Tiam1), a Rac-specific guanine nucleotide exchange factor, enhanced BMP-2-induced alkaline phosphatase activity. Further, we demonstrated that BMP-2 stimulated Rac1 activity. These results indicate that the activation of Rac1 attenuates osteoblastic differentiation in C2C12 cells. Source

Hosen N.,Osaka University
International Journal of Hematology | Year: 2013

Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells. As in other cancers, MM plasma cells are thought to be derived from MM-initiating cells, although these remain unidentified. MM patients harbor phenotypic CD19+ B cells expressing the immunoglobulin gene sequence and the idiotype unique to the individual myeloma clone. Some previous studies have reported that CD19+ clonotypic B cells can serve as MM-initiating cells. However, we and another group have recently showed that CD19+ B cells from many MM patients do not reconstitute MM disease upon transplantation into NOD/SCID IL2Rγc-/-mice. In the SCID-rab and SCID-hu models, which enable engraftment of human MM in vivo, CD19-CD38++ plasma cells engrafted and rapidly propagated MM, while engraftment of CD19+ B cells was not detected. Both CD138- and CD138+ plasma cells have the potential to propagate MM clones in vivo in the absence of CD19+ B cells. Distinct from acute myeloid leukemia-initiating cells, which are derived from undifferentiated stem or progenitor cells, MM-initiating cells are derived from plasma cells, which are terminally differentiated cells. An improved understanding of how the bone marrow microenvironment supports MM-initiating plasma cells, which can initiate MM disease in the SCID-hu (or rab) model, is thus now essential. © The Japanese Society of Hematology 2013. Source

Kemp L.E.,University of Geneva | Yamamoto M.,Osaka University | Soldati-Favre D.,University of Geneva
FEMS Microbiology Reviews | Year: 2013

Rhoptries are club-shaped secretory organelles located at the anterior pole of species belonging to the phylum of Apicomplexa. Parasites of this phylum are responsible for a huge burden of disease in humans and animals and a loss of economic productivity. Members of this elite group of obligate intracellular parasites include Plasmodium spp. that cause malaria and Cryptosporidium spp. that cause diarrhoeal disease. Although rhoptries are almost ubiquitous throughout the phylum, the relevance and role of the proteins contained within the rhoptries varies. Rhoptry contents separate into two intra-organellar compartments, the neck and the bulb. A number of rhoptry neck proteins are conserved between species and are involved in functions such as host cell invasion. The bulb proteins are less well-conserved and probably evolved for a particular lifestyle. In the majority of species studied to date, rhoptry content is involved in formation and maintenance of the parasitophorous vacuole; however some species live free within the host cytoplasm. In this review, we will summarise the knowledge available regarding rhoptry proteins. Specifically, we will discuss the role of the rhoptry kinases that are used by Toxoplasma gondii and other coccidian parasites to subvert the host cellular functions and prevent parasite death. Apicomplexan parasites secrete kinases from apical secretory organelles to take over their host cell and manipulate their surroundings. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved. Source

Tachibana Y.,RMIT University | Tachibana Y.,Japan Science and Technology Agency | Tachibana Y.,Osaka University | Vayssieres L.,Xian Jiaotong University | Durrant J.R.,Imperial College London
Nature Photonics | Year: 2012

Hydrogen generated from solar-driven water-splitting has the potential to be a clean, sustainable and abundant energy source. Inspired by natural photosynthesis, artificial solar water-splitting devices are now being designed and tested. Recent developments based on molecular and/or nanostructure designs have led to advances in our understanding of light-induced charge separation and subsequent catalytic water oxidation and reduction reactions. Here we review some of the recent progress towards developing artificial photosynthetic devices, together with their analogies to biological photosynthesis, including technologies that focus on the development of visible-light active hetero-nanostructures and require an understanding of the underlying interfacial carrier dynamics. Finally, we propose a vision for a future sustainable hydrogen fuel community based on artificial photosynthesis. © 2012 Macmillan Publishers Limited. All rights reserved. Source

The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT-PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1) early dorsoventral patterning by controlling bmp2b/7; (2) gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3) neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively) and ascl1a (negatively), and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4) neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate specification with patterning and morphogenetic processes occurring in the early embryo. Source

The 5-year survival rate is more than 70% for patients without distant metastasis, while it is 10-20% for those with distant metastatic disease, suggesting the essential development of effective perioperative therapy. In a combination of cetuximab and FOLFIRI, the rate of conversion to resectable liver metastases is about 30%, and oncogenic activation of intracellular signaling pathway downstream of epidermal growth factor receptor, like KRAS mutations, is an important mechanism of resistance to anti-epidermal growth factor receptor therapy. Other molecules in oncogenic signal transduction and microRNA are attracting attention as candidates for new molecular targets. A cancer stem cell theory has been advocated even in gastrointestinal tract cancer and thought to be involved in multidrug resistance via ATP-binding cassette transport and active DNA repair. Despite newly-devised therapeutic ways, curative treatment of advanced colorectal cancer (CRC) leading to development of prevention is still difficult. Currently, the most effective preventive strategy is endoscopic polypectomy. A most recent report showed removal of adenoma was conducive to a 77% lower risk for CRC after 10 years. However, another means of prevention needs to be developed for familial adenomatous polyposis and hereditary non-polyposis CRC. Adding to the micronutrients, several key molecules have been investigated as target candidates for chemoprevention. A deeper understanding of the biology of CRC has been expanded, which is resulting in the development of novel therapies. Copyright © 2012 S. Karger AG, Basel. Source

DNA polymerase epsilon (Pol ε) synthesizes the leading strands, following the CMG (Cdc45, Mcm2-7, and GINS [Go-Ichi-Nii-San]) helicase that translocates on the leading-strand template at eukaryotic replication forks. Although Pol ε is essential for the viability of fission and budding yeasts, the N-terminal polymerase domain of the catalytic subunit, Cdc20/Pol2, is dispensable for viability, leaving the following question: what is the essential role(s) of Pol ε? In this study, we investigated the essential roles of Pol ε using a temperature-sensitive mutant and a recently developed protein-depletion (off-aid) system in fission yeast. In cdc20-ct1 cells carrying mutations in the C-terminal domain of Cdc20, the CMG components, RPA, Pol α, and Pol δ were loaded onto replication origins, but Cdc45 did not translocate from the origins, suggesting that Pol ε is required for CMG helicase progression. In contrast, depletion of Cdc20 abolished the loading of GINS and Cdc45 onto origins, indicating that Pol ε is essential for assembly of the CMG complex. These results demonstrate that Pol ε plays essential roles in both the assembly and progression of CMG helicase. Source

Okamoto K.,Osaka University
Journal of Cell Biology | Year: 2014

Maintenance of organellar quality and quantity is critical for cellular homeostasis and adaptation to variable environments. Emerging evidence demonstrates that this kind of control is achieved by selective elimination of organelles via autophagy, termed organellophagy. Organellophagy consists of three key steps: induction, cargo tagging, and sequestration, which involve signaling pathways, organellar landmark molecules, and core autophagy-related proteins, respectively. In addition, posttranslational modifications such as phosphorylation and ubiquitination play important roles in recruiting and tailoring the autophagy machinery to each organelle. The basic principles underlying organellophagy are conserved from yeast to mammals, highlighting its biological relevance in eukaryotic cells. © 2014 Okamoto. Source

Hojo H.,Osaka University
Current Opinion in Structural Biology | Year: 2014

A methodology for chemical protein synthesis by ligation chemistry has become increasingly practical and applied to the synthesis of various proteins and glycoproteins for their structural and functional analyses. This is largely due to the advances in the synthesis of peptide thioester as well as to the progress in the extension of the ligation chemistry to a non-cysteine site, which are briefly summarized in this review. © 2014 Elsevier Ltd. Source

Inoue M.,Osaka University | Kaneko K.,Tokyo University of the Arts
PLoS Computational Biology | Year: 2013

Cells generally adapt to environmental changes by first exhibiting an immediate response and then gradually returning to their original state to achieve homeostasis. Although simple network motifs consisting of a few genes have been shown to exhibit such adaptive dynamics, they do not reflect the complexity of real cells, where the expression of a large number of genes activates or represses other genes, permitting adaptive behaviors. Here, we investigated the responses of gene regulatory networks containing many genes that have undergone numerical evolution to achieve high fitness due to the adaptive response of only a single target gene; this single target gene responds to changes in external inputs and later returns to basal levels. Despite setting a single target, most genes showed adaptive responses after evolution. Such adaptive dynamics were not due to common motifs within a few genes; even without such motifs, almost all genes showed adaptation, albeit sometimes partial adaptation, in the sense that expression levels did not always return to original levels. The genes split into two groups: genes in the first group exhibited an initial increase in expression and then returned to basal levels, while genes in the second group exhibited the opposite changes in expression. From this model, genes in the first group received positive input from other genes within the first group, but negative input from genes in the second group, and vice versa. Thus, the adaptation dynamics of genes from both groups were consolidated. This cooperative adaptive behavior was commonly observed if the number of genes involved was larger than the order of ten. These results have implications in the collective responses of gene expression networks in microarray measurements of yeast Saccharomyces cerevisiae and the significance to the biological homeostasis of systems with many components. © 2013 Inoue and Kaneko. Source

Recently, left ventricular assist devices (LVADs) have become a viable therapeutic approach as a bridge to cardiac transplantation, as well as destination therapy or as part of the bridge to recovery. In Japan, paracorporeal pneumatic devices are the only choice for such therapy, as implantable LVADs are not yet generally available due to device lag, which represents a serious problem in this field. Clinical trials of four different continuous-flow pumps, both axial and centrifugal flow types, were completed at about the same time, and two of those devices, DuraHeart and EVAHEART, have already been approved for use in Japan. Thus, reports of advanced treatment for severe heart failure with these devices are expected. The DuraHeart (Terumo Heart, Ann Arbor, MI, USA) and another device named the HeartWare (HeartWare Inc, Miami Lakes, FL, USA) are so-called third-generation devices, as they have achieved miniaturization and improvements in performance from the use of magnetic levitation. Based on our experiences from both clinical research and experimental use, we herein discuss the DuraHeart and HeartWare devices, with a focus on the clinical outcomes and management strategies. Because of the long waiting period for heart transplantation in Japan, these two devices are considered to have important roles in the near future for the treatment of severe heart failure, and a comprehensive strategy for LVAD therapy including such third-generation implantable devices is expected. © 2014, Springer Japan. Source

Kaneda Y.,Osaka University
OncoImmunology | Year: 2013

A replication-incompetent hemagglutinating virus of Japan (HVJ) envelope (HVJ-E) induces apoptosis selectively in cancer cells. Fragments of the viral RNA genome transported by HVJ-E are recognized by retinoic acid-inducible gene I (RIG-I) and mitochondrial antiviral signaling (MAVS). Specific pro-apoptotic factor are selectively upregulated in cancer cells downstream of the RIG-I/MAVS pathway. © 2013 Landes Bioscience. Source

Akira S.,Osaka University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. © 2011 The Royal Society. Source

Sugimoto N.,Osaka University
Journal of Fluid Mechanics | Year: 2010

This paper develops a general theory for linear propagation of acoustic waves in a gas enclosed in a two-dimensional channel and in a circular tube subject to temperature gradient axially and extending infinitely. A narrow-tube approximation is employed by assuming that a typical axial length is much longer than a span length, but no restriction on a thickness of thermoviscous diffusion layer is made. For each case, basic equations in this approximation are reduced to a spatially one-dimensional equation in terms of an excess pressure by making use of a method of Fourier transform. This equation, called a thermoacoustic-wave equation, is given in the form of an integro-differential equation due to memory by thermoviscous effects. Approximations of the equations for a short-time and a long-time behaviour from an initial state are discussed based on the Deborah number and the Reynolds number. It is shown that the short-time behaviour is well approximated by the equation derived previously by the boundary-layer theory, while the long-time behaviour is described by new diffusion equations. It is revealed that if the diffusion layer is thicker than the span length, the thermoviscous effects give rise to not only diffusion but also wave propagation by combined action with temperature gradient, and that negative diffusion may occur if the gradient is steep. © 2010 Cambridge University Press. Source

Quenchers play an important role in the control of the acid catalytic chain reaction in chemically amplified resists, which is an indispensable technology in the high-volume production of semiconductor devices. In this study, the effects of quencher diffusion constants on the chemical gradient of latent images formed in chemically amplified resists were investigated assuming 16nm line-and-space patterns. Although it has been reported that the chemical gradient of 22nm line-and-space patterns was increased with quencher diffusion constant, it was found that the chemical gradient of 16nm line-and-space patterns was increased with the decrease of quencher diffusion constant. © 2013 The Japan Society of Applied Physics. Source

Kozawa T.,Osaka University
Japanese Journal of Applied Physics | Year: 2013

Acid diffusion length has been regarded as the most important factor in the development of chemically amplified resists used for ultrafine patterning. In this study, the acid diffusion length in chemically amplified extreme ultraviolet (EUV) resists was investigated by a Monte Carlo method in the presence of quenchers. The acid diffusion length corresponding to the highest chemical gradient, which results in the lowest line edge roughness, was investigated by varying the exposure dose, the acid generator concentration, and the effective reaction radius for deprotection. Although the optimum acid diffusion length was decreased with the increase of effective reaction radius for deprotection, it did not depend on the exposure dose or acid generator concentration. © 2013 The Japan Society of Applied Physics. Source

Tarumi R.,Osaka University
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2013

We investigated free-vibration acoustic resonance (FVAR) of two-dimensional St Venant-Kirchhoff-type hyperelastic materials and revealed the existence and structure of colour symmetry embedded therein. The hyperelastic material is isotropic and frame indifferent and includes geometrical nonlinearity in its constitutive equation. The FVAR state is formulated using the principle of stationary action with a subsidiary condition. Numerical analysis based on the Ritz method revealed the existence of four types of nonlinear FVAR modes associated with the irreducible representations of a linearized system. Projection operation revealed that the FVAR modes can be classified on the basis of a single colour (black or white) and three types of bicolour (black and white) magnetic point groups: C2v(C2v), C 2v(C2), C2v(C1h) and C 2v(C'1h). These results demonstrate that colour symmetry naturally arises in the finite amplitude nonlinear FVAR modes, and its vibrational symmetries are explained in terms of magnetic point groups rather than the irreducible representations that have been used for linearized systems. We also predicted a grey colour nonlinear FVAR mode which cannot be derived from a linearized system. © 2013 The Author(s) Published by the Royal Society. All rights reserved. Source

Suzuki T.,Osaka University
Journal of Mathematical Fluid Mechanics | Year: 2013

Compressible Euler equation is studied. First, we examine the validity of physical laws such as the conservations of total mass and energy and also the decay of total pressure. Then we show the non-existence of global-in-time irrotational solution with positive mass. © 2013 Springer Basel. Source

Tobe Y.,Osaka University
Chemical Record | Year: 2015

The development of the chemistry of non-alternant non-benzenoid hydrocarbons is reviewed in connection with the International Symposium on Novel Aromatic Compounds (ISNA) and the author's personal anecdotes. Past molecules include the classics of this class of compounds, pentalene, azulene, and heptalene, and the structurally integrated congeners such as indacenes formed by benzannelation and benzinterposition, which were extensively studied during the last century. Indenofluorene isomers constructed by benzannelation to indacenes represent present molecules, which have attracted much interest in recent years in view of their potential in optoelectronic applications. The unusual properties of the most exotic isomer, indeno[2,1-b]fluorene, are specifically described to demonstrate that the benzannelation is not simply a modification for stabilization. Finally, as future molecules, those consisting of linear and cyclic arrays of indenofluorene motifs formed by further extension are proposed. © 2014 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kubo T.,Osaka University
Chemical Record | Year: 2015

The phenalenyl radical is a polycyclic aromatic hydrocarbon (PAH) radical. Owing to its widely distributed spin structure, phenalenyl is relatively stable compared to other hydrocarbon radicals and has been studied from the viewpoint of its application to electroconductive and magnetic materials. In addition, a strong intermolecular spin-spin coupling nature is another feature of phenalenyl. This account summarizes my studies so far into PAH radicals containing the phenalenyl scaffold in terms of their amphoteric redox properties and singlet biradical character, which strongly rely on the characteristic electronic structure, that is, non-bonding character and sixfold symmetry of a singly occupied molecular orbital of the phenalenyl radical. © 2014 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kubo T.,Osaka University
Chemistry Letters | Year: 2015

Elusive nature in spin state is a feature of singlet biradical molecules and arises from the weak coupling of unpaired electrons. This highlight review focuses on recent advances in experimental approaches for elucidating the electronic structure and properties of singlet biradical molecules having quinoid skeletons. © 2015 The Chemical Society of Japan. Source

Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort. We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity. These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection. Source

Kawai T.,Osaka University
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2011

Chronic kidney disease (CKD) is caused by various risk factors of cardiovascular disease (CVD). The estimated glomerular filtration rate (eGFR) is commonly used for the evaluation of the renal function in patients with CKD; however, it is difficult to assess the pathogenesis of CKD and predict the renal prognosis accurately using only eGFR. The resistive index (RI) in renal Doppler ultrasonography (RDU) is thought to be a good indicator of renal vascular resistance caused by atherosclerosis. In the present study, we investigated whether RI could be used to evaluate the pathogenesis of renal damage and predict the renal prognosis and investigated the correlation between RI and blood pressure (BP) fluctuations in patients with or without hypertension. The total study population included 194 patients (mean age: 66.2 years), who underwent RDU in our hospital ward between February 2009 and July 2010. We investigated the correlation between RI and multiple clinical parameters, including ambulatory blood pressure monitoring (ABPM). RI significantly correlated with age, eGFR, diastolic BP, pulse pressure and level of albuminuria. Patients with diabetes mellitus (DM) showed a significantly higher RI than patients without DM, although their eGFR was similar; thus, DM might accelerate renal vascular damage and RI could detect earlier changes of vascular damage proceeding the time eGFR is reduced. Regarding ABPM, patients with a larger morning surge [systolic blood pressure (SBP) in the early morning--lowest SBP during sleep] showed a significantly higher RI. The present study indicated that RI might be very useful for the evaluation of very early renal damage more effectively than eGFR and that diurnal BP change might be partly due to the progression of atherosclerotic change in the kidney evaluated by RI. Source

Tano Y.,Osaka University | Ohji M.,Shiga University of Medical Science
Acta Ophthalmologica | Year: 2010

Purpose: To evaluate the efficacy and safety of intravitreal ranibizumab for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in Japanese patients. Methods: This open-label, multicentre, Phase I/II study enroled patients into Group A (single injection of ranibizumab nonrandomized doses of 0.3 or 0.5 mg followed by 11 monthly injections of the same dose) and Group B (12 monthly injections of ranibizumab randomized to 0.3 or 0.5 mg). The primary efficacy endpoint was the mean change from baseline in best-corrected visual acuity (BCVA) score at Month 6. Safety was evaluated in all patients who received ranibizumab. Results: Of 88 patients enroled, 12 entered Group A (six per dose) and 76 entered Group B (0.3 mg: n = 35; 0.5 mg: n = 41). Mean change from baseline in BCVA was significantly increased for both doses (Group B) at Month 6 (0.3 mg: +8.1 letters, p = 0.0006; 0.5 mg: +9.0 letters, p < 0.0001) and Month 12 (0.3 mg: +9.5 letters, p = 0.0001; 0.5 mg: +10.5 letters, p < 0.0001). At Month 12, one patient (0.3 mg) and 0 patients (0.5 mg) lost ≥15 letters, while 37.1% (0.3 mg) and 31.7% (0.5 mg) of patients gained ≥15 letters. Ocular serious adverse events (SAEs) of the study eye were reported in 1 and 2 patients in the 0.3- and 0.5-mg groups, respectively. Nonocular SAEs were experienced by 2 and 5 patients in the 0.3- and 0.5-mg groups, respectively. No cases of endophthalmitis were reported. Conclusion: Ranibizumab was effective and well tolerated in Japanese patients with subfoveal CNV secondary to AMD. © 2010 Acta Ophthalmol. Source

Kuno Y.,Osaka University
Progress of Theoretical and Experimental Physics | Year: 2013

Anew experimental search for the charged-lepton-flavor-violating process of neutrinoless muonto- electron conversion by J-PARC E21 (the COMET experiment), which aims at a factor of 10 000 improvement over the current limit, is described, together with the physics motivation of charged lepton flavor violation. The first-stage approach of the COMET experiment (COMET Phase-I), which has recently been taken for earlier realization of the measurement, is also mentioned. © The Author(s) 2013. Source

Tamii A.,Osaka University
Acta Physica Polonica B | Year: 2013

The electric dipole (E1) response of 208Pb has been precisely determined by proton inelastic scattering measurement at very forward angles. The electric dipole polarizability, which is an inversely energy-weighted sum-rule of the electric dipole strength, has been extracted as 20:1±0:6 fm3. The data has been used to constrain the neutron skin thickness of 208Pb as 0:168 ± 0:22 fm and the slope parameter of the symmetry energy as L = 46 ± 15 MeV. The determination of the slope parameter is important for nuclear physics as well as for astrophysical simulations related to neutron stars. Source

Naumov P.,Osaka University
Topics in Current Chemistry | Year: 2012

X-ray photodiffraction (in the chemical literature also referred to as photocrystallography), which is based on the combination of X-ray diffraction methods with samples excited by UV or visible light to solve fundamental photochemical or photophysical issues, has developed in the last couple of decades into a very promising technique for direct observation of photoinduced chemical species in the solid state. The capability of providing direct information on very small perturbations in atomic positions and thus on the minute changes in molecular geometry during (or as a consequence of) photoexcitation appears to be the most important asset of this emerging analytical technique. When combined with other physicochemical methods, X-ray photodiffraction can be a powerful tool for analysis of steady-state photoinduced structures as well as slow or very fast time-dependent phenomena. Despite being a very useful approach, however, due to a number of practical requirements that it places with regard to the system to be studied, at the present stage of developments the technique is not widely and indiscriminately applicable to any photoinduced process. In some particular chemical systems the inherent pitfalls could be practically overcome by practical or theoretical means. In this short chapter, the basic principles of X-ray photodiffraction are briefly summarized, and the prospects of its application to "physical" and "chemical" problems is illustrated with selected examples from recent literature. Some possible future developments and alternative approaches with this and related methods are also presented. © 2011 Springer-Verlag Berlin Heidelberg. Source

Ichihashi N.,Osaka University
Cold Spring Harbor perspectives in biology | Year: 2010

Understanding the origin of life requires knowledge not only of the origin of biological molecules such as amino acids, nucleotides and their polymers, but also the manner in which those molecules are integrated into the organized systems that characterize cellular life. In this article, we introduce a constructive approach to understand how biological molecules can be arranged to achieve a higher-order biological function: replication of genetic information. Source

Haba N.,Osaka University | Takahashi R.,Max Planck Institute for Nuclear Physics
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

We investigate a relation among neutrino observables, three mixing angles and two mass squared differences, from a cascade texture of neutrino mass matrix. We show an allowed region of the correlation by use of current data of neutrino oscillation experiments. The relation predicts sharp correlations among neutrino mixing angles as 0.315≲sin2θ12≲0.332 and 0.480≲sin2θ23≲0.500 with a large θ13 (0.03 Source

Koide Y.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The observed sign of a deviation from the e-μ universality in tau decays suggests family gauge bosons with an inverted mass hierarchy. Under the constraints from the observed K0-K̄0 and D0-D̄0 mixing, we investigate a possibility that a mass M33 of the lightest gauge boson A33 which couples with only the third generation quarks and leptons is of the order of TeV. It is concluded that M33∼1 TeV is possible if we adopt a specific model phenomenologically. © 2013 American Physical Society. Source

Asakawa M.,Osaka University | Bass S.A.,Duke University | Muller B.,Duke University
Physical Review Letters | Year: 2013

We argue that the domain structure of deconfined QCD matter, which can be inferred from the properties of the Polyakov loop, can simultaneously explain the two most prominent experimentally verified features of the quark-gluon plasma, namely its large opacity as well as its near ideal fluid properties. © 2013 American Physical Society. Source

Unverzagt C.,University of Bayreuth | Kajihara Y.,Osaka University
Chemical Society Reviews | Year: 2013

Incremental developments in the chemistry of peptides, proteins and carbohydrates have enabled researchers to assemble entire glycoproteins with high precision. Based on sophisticated ligation chemistries pure glycoproteins bearing a single glycosylation pattern have become available. The impact of N-glycosylation on the function of glycoproteins is generally recognized but not well understood. Based on the recent advances in the synthesis of glycoproteins by chemical methods researchers can finally start to elucidate the various roles of carbohydrates in complex biomolecules in detail. © 2013 The Royal Society of Chemistry. Source

Nakano H.,Osaka University
International Journal of Molecular Sciences | Year: 2010

Photoinduced surface relief grating (SRG) formation for a single crystal of 4-aminoazobenzene was investigated. It was found that SRG could be inscribed on the (001) surface of the crystal, which might suggest that the photoinduced SRG formation is a general phenomenon observed for single crystals of azobenzene-based molecules as well as for azobenzene-based amorphous systems. In addition, the dependences of the SRG formation upon the orientation of the sample crystal and upon the polarization of the writing beams were found to be different from those observed for previously reported crystalline systems. © 2010 by the authors. Source

Tomiyama Y.,Osaka University
Blood | Year: 2014

In this issue of Blood, Stefanini and colleagues report a new way to regulate platelet function. Mice expressing a talin-1 mutant (W359A) that disrupts its binding to the NPxY motif in β3 were protected from experimental thrombosis without undermining hemostasis by decelerating αIIbβ3 activation. © 2014 by The American Society of Hematology. Source

The human genome harbors approximately 2000 genes that encode microRNAs (miRNAs), small non-coding RNAs of approximately 20-22 nt that mediate post-transcriptional gene silencing. MiRNAs are generated from long transcripts through stepwise processing by the Drosha/DGCR8, Exportin-5/RanGTP and Dicer/TRBP complexes. Given that the expression of each individual miRNA is tightly regulated, the altered expression of certain miRNAs plays a pivotal role in human diseases. For instance, germline and somatic mutations in the genes encoding the miRNA processing machinery have been reported in different cancers. Furthermore, certain miRNA genes are encoded within regions that are deleted or duplicated in individuals with chromosomal abnormalities, and the fact that the knockout of these miRNAs in animal models results in lethality or the abnormal development of certain tissues indicates that these miRNA genes contribute to the disease phenotypes. It has also been reported that mutations in miRNA genes or in miRNA-binding sites, which result in the impairment of tight regulation of target mRNA expression, cause human genetic diseases, although these cases are rare. This is in contrast to the aberrant expression of certain miRNAs that results from the impairment of transcriptional or post-transcriptional regulation, which has been reported frequently in various human diseases. The present review focuses on human diseases caused by mutations in genes encoding miRNAs and the miRNA processing machinery as well as in miRNA-binding sites. Furthermore, human diseases caused by chromosomal abnormalities that involve the deletion or duplication of regions harboring genes that encode miRNAs or the miRNA processing machinery are also introduced. © 2013 Japanese Teratology Society. Source

Minamino T.,Osaka University
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2014

For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V. Source

Di Ventra M.,University of California at San Diego | Taniguchi M.,Osaka University
Nature Nanotechnology | Year: 2016

Drugs and treatments could be precisely tailored to an individual patient by extracting their cellular- and molecular-level information. For this approach to be feasible on a global scale, however, information on complete genomes (DNA), transcriptomes (RNA) and proteomes (all proteins) needs to be obtained quickly and at low cost. Quantum mechanical phenomena could potentially be of value here, because the biological information needs to be decoded at an atomic level and quantum tunnelling has recently been shown to be able to differentiate single nucleobases and amino acids in short sequences. Here, we review the different approaches to using quantum tunnelling for sequencing, highlighting the theoretical background to the method and the experimental capabilities demonstrated to date. We also explore the potential advantages of the approach and the technical challenges that must be addressed to deliver practical quantum sequencing devices. © 2016 Macmillan Publishers Limited. Source

Morita Y.,Osaka University | Suzuki S.,Osaka City University | Sato K.,Osaka City University | Takui T.,Osaka City University
Nature Chemistry | Year: 2011

Graphene, a two-dimensional layer of sp 2-hybridized carbon atoms, can be viewed as a sheet of benzene rings fused together. Three benzene rings can be combined in three different ways, to yield linear anthracene and angular phenanthrene, where the rings share two C-C bonds, and the phenalenyl structure where three C-C bonds are shared between the rings. This third structure contains an uneven number of carbon atoms and, hence, in its neutral state, an uneven number of electrons - that is, it is a radical. All three structures may be viewed as being sections of graphene. Extension of this concept leads to an entire family of phenalenyl derivatives - 'open-shell graphene fragments' - that are of substantial interest from the standpoint of fundamental science as well as in view of their potential applications in materials chemistry, in particular quantum electronic devices. Here we discuss current trends and challenges in this field. © 2011 Macmillan Publishers Limited. All rights reserved. Source

Hamada H.,Osaka University
Seminars in Cell and Developmental Biology | Year: 2015

Physical forces play essential roles in animal development. Given that embryonic development takes place under spatial constraints, cells experience forces from neighboring cells and/or remote tissues and can transduce such forces into biochemical signals. Cells can also generate forces through active migration, movement, or deformation and thereby influence the behavior of their neighbors. Although the contribution of mechanical forces to development has been well established in general, here I will focus on recent findings that address the involvement of physical forces in body axis determination, gastrulation and cardiovascular development. © 2015 Elsevier Ltd. Source

Yamanaka N.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We evaluate the Barr-Zee-type two-loop level contribution to the fermion electric and chromo-electric dipole moments with sfermion loop in R-parity violating supersymmetric models. It is found that the Barr-Zee-type fermion dipole moment with sfermion loop acts destructively to the currently known fermion loop contribution, and that it has small effect when the mass of squarks or charged sleptons in the loop is larger than or comparable to that of the sneutrinos, but cannot be neglected if the sneutrinos are much heavier than loop sfermions. © 2012 American Physical Society. Source

Takami K.,Institute For Theoretische Physik | Rezzolla L.,Institute For Theoretische Physik | Rezzolla L.,Max Planck Institute For Gravitationsphysik | Baiotti L.,Osaka University
Physical Review Letters | Year: 2014

Determining the equation of state of matter at nuclear density and hence the structure of neutron stars has been a riddle for decades. We show how the imminent detection of gravitational waves from merging neutron star binaries can be used to solve this riddle. Using a large number of accurate numerical-relativity simulations of binaries with nuclear equations of state, we find that the postmerger emission is characterized by two distinct and robust spectral features. While the high-frequency peak has already been associated with the oscillations of the hypermassive neutron star produced by the merger and depends on the equation of state, a new correlation emerges between the low-frequency peak, related to the merger process, and the total compactness of the stars in the binary. More importantly, such a correlation is essentially universal, thus providing a powerful tool to set tight constraints on the equation of state. If the mass of the binary is known from the inspiral signal, the combined use of the two frequency peaks sets four simultaneous constraints to be satisfied. Ideally, even a single detection would be sufficient to select one equation of state over the others. We test our approach with simulated data and verify it works well for all the equations of state considered. © 2014 American Physical Society. Source

Ito T.,Osaka University | Cappelli M.A.,Stanford University
Applied Physics Letters | Year: 2012

Photon-enhanced thermionic emission from semiconducting cathodes is a promising means of increasing cathode current density in low temperature vacuum thermionic energy devices [J. W. Schwede, Nature Mater. 9, 762 (2010)]. However, the space charge resulting from high emission current densities prevents emitted electrons from reaching the collector, even with gaps as small as 100 μm and at voltages as high as 1 V. We demonstrate by particle-in-cell simulations that one possible solution to overcoming the space charge is to add cesium filling and generation of a space charge-neutralizing plasma by continuous laser excitation of the cesium resonance level. © 2012 American Institute of Physics. Source

Matsumoto C.,Osaka University
European journal of endocrinology / European Federation of Endocrine Societies | Year: 2013

3,5,3'-Triiodothyronine (T(3))-predominant Graves' disease is characterized by the increasing volume of thyroid goiter resulting in poor prognosis. Although type 1 and type 2 iodothyronine deiodinases (DIO1 and DIO2 respectively) are known to be overexpressed in the thyroid tissues of T(3)-predominant Graves' disease, the pathogenesis of this disease is still unclear. The aim of our study is to identify genes that characterize T(3)-predominant Graves' disease tissue in order to clarify the molecular mechanism of this disease. mRNAs from two thyroid tissues of both typical T(3)-predominant and common-type Graves' disease were analyzed with DNA microarrays with probes for 28 869 genes. Genes identified to be differentially expressed between the two groups were further analyzed in the second and third screenings using 70 Graves' thyroid tissues by real-time quantitative RT-PCR. Twenty-three candidate genes were selected as being differentially expressed in the first screening with microarrays. Among these, seven genes, leucine-rich repeat neuronal 1 (LRRN1), bone morphogenetic protein 8a (BMP8A), N-cadherin (CDH2), phosphodiesterase 1A (PDE1A), creatine kinase mitochondrial 2 (CKMT2), integrin beta-3 (ITGB3), and protein tyrosine phosphatase non-receptor type 4 (PTPN4), were confirmed to be differentially expressed in DIO1 or DIO2 over- and underexpressing Graves' tissues. These genes are related to the characteristics of T(3)-predominant Graves' disease, such as high titer level of serum anti-TSH receptor antibody, high free T(3) to free thyroxine ratio, and a large goiter size. They might play a role in the pathogenesis of T(3)-predominant Graves' disease. Source

Uezumi A.,Health Science University | Fukada S.-I.,Osaka University | Yamamoto N.,Aichi University | Takeda S.,National Institute of Neuroscience | Tsuchida K.,Health Science University
Nature Cell Biology | Year: 2010

Ectopic fat deposition in skeletal muscle is closely associated with several disorders, however, the origin of these adipocytes is not clear, nor is the mechanism of their formation. Satellite cells function as adult muscle stem cells but are proposed to possess multipotency. Here, we prospectively identify PDGFRα+ mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRα+ cells show efficient adipogenic differentiation both in vitro and in vivo. Reciprocal transplantations between regenerating and degenerating muscles, and co-culture experiments revealed that adipogenesis of PDGFRα+ cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFRα+ mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellitecells, has a considerable impact on muscle homeostasis. © 2010 Macmillan Publishers Limited. All rights reserved. Source

Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus—conserved across mice and humans—contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype. We identified miR-484 as the responsible gene using a combination of expression and functional analyses. Mature miR-484 was expressed during active cortical neurogenesis, and overexpression of miR-484 decreased proliferation and increased neural progenitor differentiation in vivo. Luciferase screening identified the 3'-untranslated region of protocadherin-19 (Pcdh19) as a target of miR-484. The effect of miR-484 on neurogenesis was rescued by ectopic PCDH19 expression. These results demonstrate that miR-484 promotes neurogenesis by inhibiting PCDH19. Dysregulation of neurogenesis by imbalanced miR-484/PCDH19 expression contributes to the pathogenesis of 16p13.11 microduplication syndrome.Molecular Psychiatry advance online publication, 5 July 2016; doi:10.1038/mp.2016.106. © 2016 Macmillan Publishers Limited Source

Kim S.-W.,Osaka University | Nishimura J.,High Energy Accelerator Research Organization | Nishimura J.,Graduate University for Advanced Studies | Tsuchiya A.,University of Shizuoka
Physical Review Letters | Year: 2012

We reconsider the matrix model formulation of type IIB superstring theory in (9+1)-dimensional space-time. Unlike the previous works in which the Wick rotation was used to make the model well defined, we regularize the Lorentzian model by introducing infrared cutoffs in both the spatial and temporal directions. Monte Carlo studies reveal that the two cutoffs can be removed in the large-N limit and that the theory thus obtained has no parameters other than one scale parameter. Moreover, we find that three out of nine spatial directions start to expand at some "critical time," after which the space has SO(3) symmetry instead of SO(9). © 2012 American Physical Society. Source

Miyazaki J.,University of Electro - Communications | Kinoshita S.,Osaka University
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We investigate the dynamics of exciton hopping in a CdSe/ZnS quantum dot (QD) array composed of an inhomogeneously broadened ensemble. Time- and spectrally resolved fluorescence intensities are measured by varying the excitation photon energy at the absorption edge. This method allows us to observe fluorescence from only the subdistribution of the QD ensemble, thereby allowing the dynamics of exciton hopping, which depends on the initial (donor) exciton energy, to be elucidated. Experimental results along with numerical calculations using a model of a coupled QD array show that when high-energy QDs are selectively excited, exciton energy transfer occurs repeatedly to a site of low energy, leading to a large exciton hopping length. In contrast, when the low-energy end of the QD ensemble is excited, the exciton tends to be trapped in the initial QD. Furthermore, from the analysis of the decay time of fluorescence intensities, it is suggested that there are dark QDs associated with the defect and/or off state of blinking QDs in the ensemble and energy transfer to such a site is mainly followed by quenching. © 2012 American Physical Society. Source

Yamanishi Y.,Osaka University
Dental materials : official publication of the Academy of Dental Materials | Year: 2012

Occlusal overloading is one of the causes of peri-implant bone resorption, and many studies on stress distribution in the peri-implant bone by three-dimensional finite element analysis (3D FEA) have been performed. However, the FEA models previously reported were simplified and far from representing what occurs in clinical situations. In this study, 3D FEA was conducted with simulation of the complex structure of dental implants, and the influences of neck design and connections with an abutment on peri-implant bone stress and abutment micromovement were investigated. Three types of two-piece implant CAD models were designed: external joint with a conical tapered neck (EJ), internal joint with a straight neck (IJ), and conical joint with a reverse conical neck (CJ). 3D FEA was performed with the setting of a "contact" condition at the component interface, and stress distribution in the peri-implant bone and abutment micromovement were analyzed. The shear stress was concentrated on the mesiodistal side of the cortical bone for EJ. EJ had the largest amount of abutment micromovement. While the von Mises and shear stresses around the implant neck were concentrated on the labial bone for IJ, they were distributed on the mesiodistal side of the cortical bone for CJ. CJ had the least amount of abutment micromovement. Implants with a conical joint with an abutment and reverse conical neck design may effectively control occlusal overloading on the labial bone and abutment micromovement. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved. Source

Murai T.,Osaka University
International Journal of Cell Biology | Year: 2012

Lipid rafts are cholesterol-enriched microdomains of the cell membrane and possess a highly dynamic nature. They have been involved in various cellular functions including the regulation of cell adhesion and membrane signaling through proteins within lipid rafts. The dynamic features of the cancer cell surface may modulate the malignant phenotype of cancer, including adhesion disorders and aggressive phenotypes of migration and invasion. Recently, it was demonstrated that lipid rafts play critical roles in cancer cell adhesion and migration. This article summarizes the important roles of lipid rafts in cancer cell adhesion and migration, with a focus on the current state of knowledge. This article will improve the understanding of cancer progression and lead to the development of novel targets for cancer therapy. © © 2012 Toshiyuki Murai. Source

Tumor cells are characterized by uncontrolled proliferation, often driven by activation of oncogenes, and apoptosis resistance. The oncogenic kinase inhibitor sorafenib can significantly prolong median survival of patients with advanced hepatocellular carcinoma (HCC), although the response is disease-stabilizing and cytostatic rather than one of tumor regression. Bcl-xL (B cell lymphoma extra large), an antiapoptotic member of the B cell lymphoma-2 (Bcl-2) family, is frequently overexpressed in HCC. Here, we present in vivo evidence that Bcl-xL overexpression is directly linked to the rapid growth of solid tumors. We also examined whether ABT-737, a small molecule that specifically inhibits Bcl-xL but not myeloid cell leukemia-1 (Mcl-1), could control HCC progression, especially when used with sorafenib. Administration of ABT-737, even at an in vivo effective dose, failed to suppress Huh7 xenograft tumors in mice. ABT-737 caused the levels of Mcl-1 expression to rapidly increase by protein stabilization. This appeared to be related to resistance to ABT-737, because decreasing Mcl-1 expression levels to the baseline by a small interfering RNA-mediated strategy made hepatoma cells sensitive to this agent. Importantly, administration of ABT-737 to Mcl-1 knockout mice induced severe liver apoptosis, suggesting that tumor-specific inhibition of Mcl-1 is required for therapeutic purposes. Sorafenib transcriptionally down-regulated Mcl-1 expression specifically in tumor cells and abolished Mcl-1 up-regulation induced by ABT-737. Sorafenib, not alone but in combination with ABT-737, efficiently induced apoptosis in hepatoma cells. This combination also led to stronger suppression of xenograft tumors than sorafenib alone. CONCLUSION: Bcl-xL inactivation by ABT-737 in combination with sorafenib was found to be safe and effective for anti-HCC therapy in preclinical models. Direct activation of the apoptosis machinery seems to unlock the antitumor potential of oncogenic kinase inhibitors and may produce durable clinical responses against HCC. Source

Yamamoto M.,Osaka University
Advances in Data Analysis and Classification | Year: 2012

To find optimal clusters of functional objects in a lower-dimensional subspace of data, a sequential method called tandem analysis, is often used, though such a method is problematic. A new procedure is developed to find optimal clusters of functional objects and also find an optimal subspace for clustering, simultaneously. The method is based on the k-means criterion for functional data and seeks the subspace that is maximally informative about the clustering structure in the data. An efficient alternating least-squares algorithm is described, and the proposed method is extended to a regularized method. Analyses of artificial and real data examples demonstrate that the proposed method gives correct and interpretable results. © 2012 Springer-Verlag. Source

Uchiyama S.,Osaka University
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2014

Currently many biopharmaceuticals are in use due to their high efficacy and low adverse effects. For antibody drug formulation, liquid ones are being increasingly used. This review focuses on rational liquid antibody formulation development based on the proposed aggregation mechanism of antibody, considering colloidal and conformational stabilities. This review also describes the importance of assessment of physicochemical properties including second virial coefficient of antibody solutions, for the rational and efficient formulation development. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. © 2014 Elsevier B.V. All rights reserved. Source

Yamanaka N.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

The contribution of the R-parity violating minimal supersymmetric standard model at the one-loop level to the Hg199 atomic electric dipole moment through P, CP-odd electron-nucleon (e-N) interaction is calculated. We show that the current experimental data of the Hg199 electric dipole moment give tighter constraints on some of the imaginary parts of R-parity violating coupling than those currently known. We add also the analysis of the P, CP-odd 4-quark interaction generated by R-parity violating interactions at the one-loop level, and discuss the possibility to constrain them in future experiments. © 2012 American Physical Society. Source

Ueno M.,Cincinnati Childrens Hospital Medical Center | Ueno M.,Japan Science and Technology Agency | Yamashita T.,Osaka University | Yamashita T.,Japan Science and Technology Agency
Current Opinion in Neurobiology | Year: 2014

•Microglia play bidirectional roles in neurogenesis.•Microglia control the survival and death of developing neurons.•Microglia engage in maintenance of axons and synapses.•Possible therapeutic strategy using microglia. The developing brain employs multi-step processes to construct neural circuitry. Recent studies have highlighted that microglia, traditionally known to be the resident immune cells in the brain, have essential roles in these processes, which range from neurogenesis to establishing synaptic connections. Microglia play bidirectional roles for maintaining proper circuitry: eliminating unnecessary cells, axons, and synapses, while supporting the neighboring ones. Although these processes are performed in different parts of the neuron, similar molecular mechanisms are possibly involved. This paper reviews recent progress on the knowledge of the roles of microglia in brain development, and further discusses the application of this knowledge in therapies for brain disorders and injuries. © 2014 Elsevier Ltd. Source

Gao X.,Guangdong University of Technology | Katayama S.,Osaka University
IEEE Transactions on Industrial Informatics | Year: 2014

In order to optimize the productivity of industrial manufacturing, a multisensor fusion system based on support vector machine (SVM) was researched to monitor and identify weld defects during high-power disk laser welding. Three different sensing technologies were integrated: 1) photodiode sensing for the monitoring of visible light radiation, which was generated from laser focus position; 2) ultraviolet and visible (UVV) sensing for plume and molten pool; and 3) visual sensing based on auxiliary illumination for the monitoring of the dynamic behavior of molten pool and keyhole. Time and frequency domains of the features that were extracted from the sensors constituted the eigenvector used for SVM classification. Experimental results showed that the integration of photodiode and visual sensing provided a more accurate and comprehensive estimation on the laser welding process. The proposed SVM-based approach has been proven to be efficient for inspecting defects in the laser welding process. © 2005-2012 IEEE. Source

Mann I.,Belgian Institute for Space Aeronomy | Mann I.,Osaka University
Annual Review of Astronomy and Astrophysics | Year: 2010

A fraction of the dust in the interstellarmedium (ISM) enters the heliosphere and is measured in situ from spacecraft. This review surveys the in situ measurements and discusses a hence derived model of dust in the local interstellar cloud (LIC). The LIC dustmodel bears similarities to pristine cometary dust and is characteristic of the warm ISM clouds that fill a part of the ISM in the vicinity of the Sun. Recent and future dust in situ measurements provide a basis for closely studying physical processes in the ISM surrounding the Solar System. The LIC dust is the only dust component measurable in the Solar System that was not previously incorporated in larger Solar System objects. Issues for future LIC dust studies are measuring dust fluxes at the outer heliosphere, measuring the mass distribution with meteor observations and observations from spacecraft, and measuring the LIC dust composition in situ in space. © 2010 by Annual Reviews. Source

Ohira Y.,High Energy Accelerator Research Organization | Takahara F.,Osaka University
Astrophysical Journal Letters | Year: 2010

Hα emission from supernova remnants (SNRs) implies the existence of neutral hydrogens in the ambient medium. In the precursor of an SNR shock modified by cosmic rays (CRs), upstream plasmas are pushed by the CR pressure, but neutral particles are not, so that the relative velocity appears and some neutral particles become pickup ions by the charge exchange process in the precursor. We investigate how the pickup ions generated in the precursor affect the shock structure and the particle acceleration. If the CR pressure is larger than 20% of the shock ram pressure, the compression of the subshock becomes smaller than that without pickup ions because of the pressure of the pickup ions. Moreover, even if the shock is modified by CRs, the total compression ratio can be smaller than 4. In addition, the pickup ions play an important role for the injection into the particle acceleration. If the shock is a quasi-perpendicular shock and if the multiply reflected ion acceleration occurs, the CR spectrum can be harder than that of the test particle diffusive shock acceleration below GeV. © 2010. The American Astronomical Society. All rights reserved. Source

The Nkx3.2 transcription factor promotes chondrogenesis by forming a positive regulatory loop with a crucial chondrogenic transcription factor, Sox9. Previous studies have indicated that factors other than Sox9 may promote chondrogenesis directly, but these factors have not been identified. Here, we test the hypothesis that Nkx3.2 promotes chondrogenesis directly by Sox9-independent mechanisms and indirectly by previously characterized Sox9-dependent mechanisms. C3H10T1/2 pluripotent mesenchymal cells were cultured with bone morphogenetic protein 2 (BMP2) to induce endochondral ossification. Overexpression of wild-type Nkx3.2 (WT-Nkx3.2) upregulated glycosaminoglycan (GAG) production and expression of type II collagen α1 (Col2a1) mRNA, and these effects were evident before WT-Nkx3.2-mediated upregulation of Sox9. RNAi-mediated inhibition of Nkx3.2 abolished GAG production and expression of Col2a1 mRNA. Dual luciferase reporter assays revealed that WT-Nkx3.2 upregulated Col2a1 enhancer activity in a dose-dependent manner in C3H10T1/2 cells and also in N1511 chondrocytes. In addition, WT-Nkx3.2 partially restored downregulation of GAG production, Col2 protein expression, and Col2a1 mRNA expression induced by Sox9 RNAi. ChIP assays revealed that Nkx3.2 bound to the Col2a1 enhancer element. Nkx3.2 promoted primary chondrogenesis by two mechanisms: Direct and Sox9-independent upregulation of Col2a1 transcription and upregulation of Sox9 mRNA expression under positive feedback system. Source

Okada M.,Osaka University
International Journal of Biological Sciences | Year: 2012

The non-receptor tyrosine kinase Csk serves as an indispensable negative regulator of the Src family tyrosine kinases (SFKs) by specifically phosphorylating the negative regulatory site of SFKs, thereby suppressing their oncogenic potential. Csk is primarily regulated through its SH2 domain, which is required for membrane translocation of Csk via binding to scaffold proteins such as Cbp/PAG1. The binding of scaffolds to the SH2 domain can also upregulate Csk kinase activity. These regulatory features have been elucidated by analyses of Csk structure at the atomic levels. Although Csk itself may not be mutated in human cancers, perturbation of the regulatory system consisting of Csk, Cbp/PAG1, or other scaffolds, and certain tyrosine phosphatases may explain the upregulation of SFKs frequently observed in human cancers. This review focuses on the molecular bases for the function, structure, and regulation of Csk as a unique regulatory tyrosine kinase for SFKs. Source

Fujinaga Y.,Osaka University
Journal of Biomedicine and Biotechnology | Year: 2010

Botulinum neurotoxin (BoNT) is a protein toxin (∼150 kDa), which possesses a metalloprotease activity. Food-borne botulism is manifested when BoNT is absorbed from the digestive tract to the blood stream and enters the peripheral nerves, where the toxin cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The initial obstacle to orally ingested BoNT entering the body is the epithelial barrier of the digestive tract. Recent cell biology and molecular biology studies are beginning to elucidate the mechanism by which this large protein toxin crosses the epithelial barrier. In this review, we provide an overview of the structural features of botulinum toxins (BoNT and BoNT complex) and the interaction of these toxins with the epithelial barrier. Copyright © 2010 Yukako Fujinaga. Source

Kimura T.,Osaka University
Annual Review of Condensed Matter Physics | Year: 2012

Magnetoelectric (ME) multiferroics are materials that combine coupled electric and magnetic dipoles. Studies of ME multiferroics are a time-honored research subject because of their potential for future electronic devices. Recent discoveries have revealed that ferroelectricity can be induced by complex internal arrangements of magnetic moments. This new family of multiferroics is called magnetically induced ferroelectrics. Magnetically induced ferroelectrics are known to show giant ME effects, i.e., changes in ferroelectric polarization upon application of an external magnetic field. However, their ME effects usually occur at temperatures that are too low and at applied external fields (> ∼0.1 T) that are too high to be of practical use. Thus, the quest for a robust room-temperature ME effect is a major challenge in ME research. Lately, some ferrites with hexagonal crystal structures, termed hexaferrites, have been found to show ME effects at room temperature and low magnetic fields (∼0.01 T). The results represented an important step toward practical applications using the ME effect in magnetically induced ferroelectrics. This review introduces structure, magnetism, and resulting magnetoelectricity of hexaferrite systems, which are promising candidate materials for ME devices. Copyright © 2012 by Annual Reviews. All rights reserved. Source

Matsumoto M.,Osaka University
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2012

Fiber-based all-optical signal regeneration techniques are reviewed. In the first half of the paper, amplitude regeneration schemes for ON-OFF keying signals using self-phase modulation and four-wave mixing in fibers are classified and their features are described. In the second half of the paper, focus is placed on regeneration schemes of phase-encoded signals. In particular, we discuss the performance of the regenerators in which phase information is converted to/from amplitude information and noise suppression is done on the amplitude. Usefulness of phase-preserving amplitude-only regeneration in reducing nonlinear phase noise is also discussed. Some experimental results are shown. Finally, issues in applying all-optical regeneration to real transmission systems are mentioned. © 2011 IEEE. Source

Ajiki H.,Osaka University
Journal of Physics Condensed Matter | Year: 2012

Exciton states and related optical properties of a single-walled carbon nanotube are reviewed, primarily from a theoretical viewpoint. The energies and wavefunctions of excitons are discussed using a screened Hartree-Fock approximation with an effective-mass or k p approximation. The close relationship between a long-range electron-hole exchange interaction and a depolarization effect is clarified. I discuss optical properties including the radiative lifetime of excitons, absorption spectra and radiation force. To describe these properties in a unified scheme, a self-consistent method is introduced for calculating the scattering light and induced current density due to excitons. I also briefly review experimental results on the Aharonov-Bohm effect in excitons and quasi-dark excitons excited by light polarized perpendicular to the tube axis. © 2012 IOP Publishing Ltd. Source

Morita A.,Osaka University
Science Technology and Human Values | Year: 2014

Context holds a significant place mediating the conceptual and the empirical in ethnography. This modality of knowledge has also become a significant part of science and technology studies since the rise of laboratory studies. However, conventional modes of contextualization that locate the object of study within a whole-such as within a society or culture-have become a target of suspicion and criticism since the 1980s. This led to the radical alteration of the contextualizing strategies of actor-network theory (ANT) and multisited ethnography. Anthropologist Marilyn Strathern is also responding to this crisis by renovating the practice of ethnography in a way significantly different from both strategies. Since contextualization occupies a significant place in the formation of ethnography as a representation of a larger "out there" reality, her alternative contextualization requires a new characterization of ethnography other than representation. This article tries to expound the complicated, and often perplexing, ethnography of Strathern by making an analogy with objects familiar to most science, technology, and society scholars, namely, machines. By doing so, this article argues that Strathern is opening up a new way of dealing with context that is radically different both from ANT and from multisited ethnography. © The Author(s) 2013. Source

Minamino T.,Osaka University
Circulation Journal | Year: 2012

Because ischemic heart diseases (IHDs) are a major cause of mortality and heart failure, novel therapeutic approaches are expected to improve the clinical outcomes of patients with IHDs such as acute myocardial infarction and ischemic heart failure. Brief episodes of nonlethal ischemia and reperfusion before sustained ischemia or at the onset of reperfusion can reduce ischemia-reperfusion injury. These ischemic conditioning phenomena are termed "ischemic preconditioning" and "ischemic postconditioning", respectively. Furthermore, brief episodes of nonlethal ischemia and reperfusion applied to the organ or tissue distal to the heart reduce myocardial infarct size, known as "remote ischemic conditioning". The cardioprotection afforded by these ischemic conditionings can be used to treat patients with acute myocardial infarction or cardiac operations. Extensive research has determined that autacoids (eg, adenosine, bradykinin opioid) and cytokines, their respective receptors, kinase signaling pathways and mitochondrial modulation are involved in ischemic conditioning. Modification of these factors by pharmacological agents mimics the cardioprotection by ischemic conditioning and provides a novel therapeutic intervention for IHDs. Here, the potential mechanisms of ischemic conditioning and its "proof-of-concept" translational studies are reviewed. In the near future, large, multicenter, randomized, placebo-controlled, clinical trials will be required to determine whether pharmacological and ischemic conditioning can improve the clinical outcomes of patients with IHDs. Source

Nagasawa Y.,Osaka University
Journal of Photochemistry and Photobiology C: Photochemistry Reviews | Year: 2011

Three-pulse photon echo (3PPE) experiment has been applied to liquids, amorphous, and biological systems to elucidate the origin of the spectral line-broadening mechanism of optical transitions. 3PPE is a third-order nonlinear coherent optical process which is a part of the degenerate four-wave-mixing (DFWM) technique. Originally it was developed to determine electronic dephasing time in low-temperature glass and/or amorphous systems and simultaneously applied to solvation dynamics and/or spectral diffusion in condensed phase. Moreover, when a sufficiently short femtosecond laser pulse is utilized, it could also induce and control intramolecular coherent nuclear wavepacket motions. In the present review, we introduce the development and application of 3PPE spectroscopy in condensed phase, together with its basic background. © 2011 Elsevier B.V. Source

Suzuki T.,Osaka University
Chemical Reviews | Year: 2011

The progress made in the area of iridium-catalyzed oxidation is discussed. Gelman reported the oxidation of secondary alcohols using an air-stable Ir pincer complex and Jensen developed a dihydride iridium PCP pincer complex and applied it to the oxidation of phenylethanol in the presence of tert-butylethylene as an oxidant. Lin reported the oxidative lactonization of 1,4- and 1,5-diols using IrH5(P-iPr3)2 with acetone as the oxidant. Suzuki reported a mild Tishchenko-type reaction using an iridium aminoalkoxide catalyst and Williams reported the one-pot synthesis of amides from alcohols. Williams reported that N-alkylation of phenylethylamine and tryptamine with alcohols proceeds with the [Ir(cod)Cl]2-dppf catalyst system. Ishii reported the synthesis of quinolines and pyroles from aminoalcohols and ketones in the presence of several iridium catalyst systems and KOH without any solvent. Source

Kozawa T.,Osaka University
Japanese Journal of Applied Physics | Year: 2012

The line edge roughness (LER) of resist patterns is a critical issue in the high-volume production of semiconductor devices. LER is inversely proportional to the square root of exposure dose. However, LER cannot be reduced below a certain value when exposure dose is increased or when sensitivity is decreased. In this study, the cause of this lower limit was investigated by Monte Carlo simulation. The dependences of the lower limit of LER on acid generator concentration, feature size, optical image contrast, and flare intensity were clarified. The decomposition effect of acid generators during exposure is a dominant factor for the lower limit of LER in the relationship between LER and exposure dose (or sensitivity). © 2012 The Japan Society of Applied Physics. Source

Nakano T.,Osaka University
IEEE Transactions on Systems, Man and Cybernetics Part C: Applications and Reviews | Year: 2011

The emerging interdisciplinary area of biologically inspired network systems research is reviewed. Examples of such systems found in the literature are grouped into two classes: in silico and in vitro/vivo network systems. For each class, background knowledge is provided concerning the biological systems, mechanisms, or materials used, and the manner in which they are applied to the design of the network systems is reviewed. Conclusions are drawn with the aim of providing future challenges for each class of biologically inspired network systems. © 2010 IEEE. Source

Naylor W.,Osaka University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2015

We separate Maxwell's equations for background media that allow for both electric and magnetic time dependence in a generalized Lorenz gauge. In a process analogous to the dynamical Casimir effect (DCE) we discuss how surface plasmon polaritons (SPPs) can be created out of vacuum via the time-dependent variation of a dielectric and magnetic insulator at a metal interface for TM and TE branches, respectively. We suggest how to extend currently proposed DCE experiments to set up and detect these excitations. Numerical simulations (without any approximation) indicate that vacuum-excited SPPs can be of a similar magnitude to the photon creation rate in such experiments. Potential benefits of detecting vacuum-excited SPPs, as opposed to DCE photons, are that parametric enhancement does not require a sealed cavity in the axial direction and the detection apparatus might be able to use simple phase-matching techniques. For the case of constant permeability μ, TM branch SPPs and photons do not suffer from detuning and attenuation like TE photons. © 2015 American Physical Society. Source

Kaisho T.,Osaka University | Kaisho T.,RIKEN
Vaccine | Year: 2012

Pathogen sensors such as Toll-like receptors (TLRs) detect microorganism- or host-derived conserved molecular structures, including lipids or nucleic acids and provoke activation of Ag presenting cells such as dendritic cells (DCs). Several synthetic TLR ligands, especially oligonucleotides, are being developed as promising vaccines for infectious diseases, cancers or allergies. DCs are heterogeneous and consist of various subsets, each of which expresses a subset-specific repertoire of TLRs and responds to the TLR signaling in a subset-specific manner. Furthermore, each DC subset expresses a set of chemokine receptors that regulate its function and behavior. Here I review the functions of two DC subsets and how chemokine receptors function in these subsets. One is the plasmacytoid DC (pDC), which expresses nucleic acid sensing receptors TLR7 and TLR9 and secretes large amounts of type I interferons in response to TLR7/9 signaling. The other is splenic CD8α+ conventional DC (cDC). This DC subset expresses lipid sensors, TLR2 and TLR4, and nucleic acid sensors, TLR3, TLR9 and TLR13 and is specialized for antigen crosspresentation. Several chemokine receptors are differentially expressed on these DC subsets. The homologues of these murine DC subsets are also found in humans. Understanding how these DC subsets function and respond to TLR ligands and chemokines should be important for development of effective vaccines. © 2012 Elsevier Ltd. Source

This paper proposes a low polarization- or phase-dependent fiber parametric amplifier system with a clamped output phase, which consists of an orthogonally pumped nonlinear fiber and a fiber loop with a polarization beam splitter. Numerical calculations show that the proposed system exhibits a constant output phase, low insensitive to the signal input phase or polarization state. © 2015 Optical Society of America. Source

Hayashi M.,Nagoya Institute of Technology | Sano M.,Nagoya Institute of Technology | Funahashi Y.,Osaka University | Nakamura S.,Nagoya Institute of Technology
Angewandte Chemie - International Edition | Year: 2013

Managing the Mannich: The first enantioselective vinylogous Mannich reaction of siloxyfurans with ketimines derived from unactivated ketones has been developed. Excellent yields and enantioselectivities were obtained using a new class of readily accessible cinchona alkaloid amide/Cu(OAc)2 catalysts on a range of substrates. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kondo S.,Osaka University | Miura T.,Kyoto University
Science | Year: 2010

The Turing, or reaction-diffusion (RD), model is one of the best-known theoretical models used to explain self-regulated pattern formation in the developing animal embryo. Although its real-world relevance was long debated, a number of compelling examples have gradually alleviated much of the skepticism surrounding the model. The RD model can generate a wide variety of spatial patterns, and mathematical studies have revealed the kinds of interactions required for each, giving this model the potential for application as an experimental working hypothesis in a wide variety of morphological phenomena. In this review, we describe the essence of this theory for experimental biologists unfamiliar with the model, using examples from experimental studies in which the RD model is effectively incorporated. Source

Nishida M.,Osaka University
Journal of High Energy Physics | Year: 2015

Abstract: Frustration is an important phenomenon in condensed matter physics because it can introduce a new order parameter such as chirality. Towards understanding a mechanism of the frustration in strongly correlated systems, we study a holographic superconductor model with three scalar fields and an interband Josephson coupling, which is important for the frustration. We analyze free energy of solutions of the model to determine ground states. We find chiral ground states, which have nonzero chirality. © 2015, The Author(s). Source

The fluctuation of the line edge of resist patterns, called line edge roughness (LER), has been the most serious problem in the development of next-generation lithography. The major root cause of LER is the chemical inhomogeneity at the boundary between the insoluble and soluble regions of the resist. In this study, the stochastic effect induced in the processes of formation of resist patterns was investigated using a Monte Carlo method. The relative standard deviation of acid concentration was smaller than that of absorbed photons. The relative standard deviation of protected units was smaller than that of acid concentration. By comparing the simulation results with the reported values of LER, it was found that the stochastic effect is further reduced in the development and rinse processes. © 2012 The Japan Society of Applied Physics. Source

Yang C.,Sichuan University | Inoue Y.,Osaka University
Chemical Society Reviews | Year: 2014

Supramolecular photochirogenesis is a rapidly growing interdisciplinary area of science at the boundary of photochemistry, asymmetric synthesis and supramolecular chemistry. The major advantage of supramolecular photochirogenesis over the conventional molecular one is entropic in origin, being achieved by preorganizing substrate(s) in the ground state and manipulating subsequent photochemical transformation by weak but non-transient interactions in chiral supramolecular media. The chirality transfer often becomes more efficient through the cooperative non-covalent interactions and the confinement by host in both ground and excited states. Thus, all of the ground- and excited-state events, including complexation stoichiometry and affinity, chiroptical properties, photophysical behaviour and photochemical reactivity, jointly play pivotal roles in supramolecular photochirogenesis. This may appear to cause complication but in reality expands the range of manipulable factors and available experimental/theoretical tools for elucidating the mechanism and controlling photochirogenic processes both thermodynamically and kinetically, from which some new concepts/methodologies unique to supramolecular photochemistry, such as non-sensitizing catalytic photochirogenesis and wavelength-controlled photochirogenesis, have already been developed. In this review, we will discuss the recent progress and future perspective of supramolecular photochirogenesis. This journal is © the Partner Organisations 2014. Source

Hatano N.,Kansai Electric Power Co. | Ise T.,Osaka University
IEEE Transactions on Power Delivery | Year: 2010

This paper presents a control scheme of cascaded H-bridge STATCOM in three-phase power systems. Cascaded H-bridge STATCOM has merits in point of switching losses, output harmonics, and the number of circuit components. But every H-bridge cell has isolated dc capacitors. So the balancing problem of capacitor voltages exists. Since STATCOM is often requested to operate under asymmetrical condition by power system faults, capacitor voltage balancing between phase clusters is particularly important. Solving this problem, a technique using zero-sequence voltage and negative-sequence current is proposed. By this scheme, the STATCOM is allowed to operate under asymmetrical conditions by power system faults. The validity is examined by digital simulation under one line and two-lines fault circuit condition. © 2010 IEEE. Source

Takeuchi Y.,Osaka University
International Journal of Innovative Computing, Information and Control | Year: 2012

In this paper, we study an optimization problem for the observations of the stationary LQG stochastic control systems that employ the stationary Kalman filter. The performance criterion for the selection of the gain matrix is assumed to be the sum of the LQG regulator performance value, which is a linear function of the estimation error co-variance matrix, and a quadratic function of the observation gain matrix. By introducing the eigenvalues-eigenvectors representation of a nonnegative definite symmetric matrix that is a function of the gain matrix, we reformulate the problem as that of optimization with respect to a pair of orthogonal and diagonal matrices. The condition of optimality for this problem is derived under a weaker assumption than already known. For easy numerical calculations, we represent the orthogonal matrix in a multi-dimensional polar coordinates system with angular parameters. Moreover, we apply the connection rule of the angular parameters that was previously shown by the author. Using this rule, we can always find a point in the domain of the angular parameters, with the same value of the performance criterion, from any point outside the domain. A numerical example is provided for better understanding of the results of this paper. © 2012 ISSN 1349-4198. Source

Fujita Y.,Osaka University | Ohira Y.,High Energy Accelerator Research Organization
Astrophysical Journal | Year: 2012

We study non-thermal emissions from cool cores in galaxy clusters. We adopted a recent model in which cosmic rays (CRs) prevail in the cores and stably heat them through CR streaming. The non-thermal emissions come from the interaction between CR protons and intracluster medium (ICM). Comparison between the theoretical predictions and radio observations shows that the overall CR spectra must be steep, and most of the CRs in the cores are low-energy CRs. Assuming that the CRs are injected through active galactic nucleus activities, we study the nature of the shocks that are responsible for the CR acceleration. The steep CR spectra are likely to reflect the fact that the shocks travel in hot ICM with fairly small Mach numbers. We also study the dependence on the CR streaming velocity. The results indicate that synchrotron emissions from secondary electrons should be observed as radio mini-halos in the cores. In particular, low-frequency observations (e.g., LOFAR) are promising. However, the steepness of the spectra makes it difficult to detect non-thermal X-ray and gamma-ray emissions from the cores. The low-energy CRs may be heating optical filaments observed in the cores. © 2012. The American Astronomical Society. All rights reserved. Source

Kusunose M.,Kwansei Gakuin University | Takahara F.,Osaka University
Astrophysical Journal | Year: 2012

Recent observations of Sgr A* by Fermi and HESS have detected steady γ-ray emission in the GeV and TeV bands. We present a new model to explain the GeV γ-ray emission by inverse Compton scattering by nonthermal electrons supplied by the NIR/X-ray flares of Sgr A*. The escaping electrons from the flare regions accumulate in a region with a size of 10 18 cm and magnetic fields of ≲ 10-4 G. Those electrons produce γ-rays by inverse Compton scattering off soft photons emitted by stars and dust around the central black hole. By fitting the GeV spectrum, we find constraints on the magnetic field and the energy density of optical-UV radiation in the central 1 pc region around the supermassive black hole. While the GeV spectrum is well fitted by our model, the TeV γ-rays, whose spectral index is different from that of the GeV emission, may be from different sources such as pulsar wind nebulae. © 2012 The American Astronomical Society. All rights reserved. Source

Maeda N.,Osaka University
Molecular Aspects of Medicine | Year: 2012

The discovery of water channel protein (aquaporin [AQP]) has made a great impact on life sciences. So far, 13 AQPs have been identified in human. AQP3, 7, 9, and 10 are subcategorized as aquaglyceroporins which permeabilize glycerol as well as water. Many investigators have demonstrated that AQPs play a crucial role in the maintenance of water homeostasis, but the physiological significance of some AQPs as glycerol channels remains elusive. Adipocyte is a major source of glycerol, which is one of the substrates for hepatic gluconeogenesis. This review focuses on recent studies on glycerol metabolism through AQP7 and AQP9, and briefly discusses the importance of glycerol channel in adipocytes, liver, and heart. © 2012 Elsevier Ltd. All rights reserved. Source

Nagai T.,Chiba University | Komuro I.,Osaka University
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012

Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Many new therapeutic strategies, including cell transplantation, gene delivery, and cytokines or other small molecules, have been explored to treat HF. Recent advancement of our understanding of the molecules that regulate cardiac function uncover many of the therapeutic key molecules to treat HF. Furthermore, a theory of paracrine mechanism, which underlies the beneficial effects of cell therapy, leads us to search novel target molecules for genetic or pharmacological strategy. Gene therapy means delivery of genetic materials into cells to achieve therapeutic effects. Recently, gene transfer technology in the cardiovascular system has been improved and several therapeutic target genes have been started to examine in clinical research, and some of the promising results have been emerged. Among the various bioactive reagents, cytokines such as granulocyte colony-stimulating factor and erythropoietin have been well examined, and a number of clinical trials for acute myocardial infarction and chronic HF have been conducted. Although further research is needed in both preclinical and clinical areas in terms of molecular mechanisms, safety, and efficiency, both gene and cytokine therapy have a great possibility to open the new era of the treatment of HF. © 2012 the American Physiological Society. Source

Kin K.,Osaka University
Journal of the American Heart Association | Year: 2012

Atherosclerotic abdominal aortic aneurysm (AAA) is a progressive, gradual aortic rupture that results in death in the absence of surgical intervention. Key factors that regulate initiation and progression of AAA are unknown, making targeted interventions difficult. MicroRNAs play a fundamental role in atherosclerosis, and atherosclerotic coronary artery disease is characterized by tissue- and plasma-specific microRNA signatures. However, little is known about microRNAs involved in AAA pathology. This study examined tissue and plasma microRNAs specifically associated with AAA. AAA and normal wall tissues were sampled from patients undergoing AAA repair (n=13; mean age, 68±6 years) and aortic valve replacement surgery (n=7; mean age, 66±4 years), respectively. MicroRNA expression was assessed by high-throughput microRNA arrays and validated by real-time polymerase chain reaction for individual microRNAs that showed significant expression differences in the initial screening. MicroRNAs related to fibrosis (miR-29b), inflammation (miR-124a, miR-146a, miR-155, and miR-223), and endothelium (miR-126, let-7 family members, and miR-21) were significantly upregulated in AAA tissue. Significant negative correlations were seen in expression levels of monocyte chemoattractant protein-1 and miR-124a, -146a, and -223; tumor necrosis factor-α and miR-126 and -223; and transforming growth factor-β and miR-146a. Expression of microRNAs, such as miR-29b, miR-124a, miR-155, and miR-223, that were upregulated in AAA tissue was significantly reduced in plasma of patients with AAA (n=23; mean age, 72±9 years) compared to healthy controls (n=12; mean age, 51±11 years) and patients with coronary artery disease (n=17; mean age, 71±9 years). The expression of some microRNAs was specifically upregulated in AAA tissue, warranting further studies on the microRNA function in AAA pathogenesis and on the possibility of using a microRNA biomarker for AAA diagnosis. Source

In this paper, we study robust failure diagnosis of discrete event systems. Given a set of possible models, each of which has its own nonfailure specification, we consider the existence of a single diagnoser such that, for all possible models, it detects any occurrence of a failure within a uniformly bounded number of steps. We call such a diagnoser a robust diagnoser. We introduce a notion of robust diagnosability, and prove that it serves as a necessary and sufficient condition for the existence of a robust diagnoser. We then present an algorithm for verifying the robust diagnosability condition. © 2012 Elsevier Ltd. All rights reserved. Source

Aoki S.,University of Tsukuba | Fukaya H.,Osaka University | Taniguchi Y.,University of Tsukuba
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We reconsider constraints on the eigenvalue density of the Dirac operator in the chiral-symmetric phase of two-flavor QCD at finite temperature. To avoid possible ultraviolet divergences, we work on a lattice, employing the overlap Dirac operator, which ensures the exact "chiral" symmetry at finite lattice spacings. Studying multipoint correlation functions in various channels and taking their thermodynamical limit (and then taking the chiral limit), we obtain stronger constraints than those found in the previous studies: both the eigenvalue density at the origin and its first and second derivatives vanish in the chiral limit of two-flavor QCD. In addition, we show that the axial U(1) anomaly becomes invisible in susceptibilities of scalar and pseudoscalar mesons, suggesting that the second-order chiral phase transition with the O(4) scaling is not realized in two-flavor QCD. Possible lattice artifacts when the nonchiral lattice Dirac operator is employed are briefly discussed. © 2012 American Physical Society. Source

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

In a series of papers, we have established the existence of two gauge-invariant decompositions of the nucleon spin, which are physically nonequivalent. The orbital angular momenta of quarks and gluons appearing in these two decompositions are gauge-invariant dynamical orbital angular momenta and "generalized" canonical orbital angular momenta with gauge-invariance, respectively. The key quantity, which characterizes the difference between these two types of orbital angular momenta is what-we-call the potential angular momentum. We argue that the physical meaning of the potential angular momentum in the nucleon can be made more transparent, by investigating a related but much simpler example from electrodynamics. We also make clear several remaining issues in the spin and momentum decomposition problem of the nucleon. We clarify the relationship between the evolution equations of orbital angular momenta corresponding to the two different decompositions above. We also try to answer the question whether the two different decompositions of the nucleon momentum really lead to different evolution equations, thereby predicting conflicting asymptotic values for the quark and gluon momentum fractions in the nucleon. © 2012 American Physical Society. Source

Horiguchi Y.,Osaka University
Current Topics in Microbiology and Immunology | Year: 2012

Atrophic rhinitis is a widespread and economically important swine disease caused by Pasteurella multocida and Bordetella bronchiseptica. The disease is characterized by atrophy of the nasal turbinate bones, which results in a shortened and deformed snout in severe cases. P. multocida toxin and B. bronchiseptica dermonecrotic toxin have been considered to independently or cooperatively disturb the osteogenesis of the turbinate bone by inhibiting osteoblastic differentiation and/or stimulating bone resorption by osteoclasts. Recently, the intracellular targets and molecular actions of both toxins have been clarified, enabling speculation on the intracellular signals leading to the inhibition of osteogenesis. © 2012 Springer-Verlag Berlin Heidelberg. Source

Walczak H.,Imperial College London | Iwai K.,Osaka University | Dikic I.,Goethe University Frankfurt
BMC Biology | Year: 2012

Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation. © 2012 Walczak et al; licensee BioMed Central Ltd. Source

Koh S.,Osaka University
Clinical Ophthalmology | Year: 2015

Diquafosol is a drug used for dry eye treatment with a novel mechanism of action. It stimulates the secretion of tear fluid and mucin on the ocular surface, thus enabling us to selectively treat the tear film layer, playing an important role in the establishment of the concept of “Tear Film Oriented Therapy (TFOT)”, an effective therapeutic approach to dry eye in Japan. The 3% diquafosol ophthalmic solution has been widely used for the treatment of dry eye in clinical practice, and it is currently available in Japan and South Korea. This review provides an overview of the clinical utility of 3% diquafosol ophthalmic solution, focusing on the results of clinical studies on various types of dry eye, including aqueous-deficient dry eye, short tear film breakup time-type dry eye, and post dry eye after laser in situ keratomileusis. It also introduces the additive effect of diquafosol on sodium hyaluronate monotherapy for dry eye, and the effect of 3% diquafosol ophthalmic solution for dry eye-related conditions. Additionally, it summarizes the ocular effects of diquafosol in healthy human eyes. Lastly, the importance of improving tear film stability in dry eye treatment, as well as general advances in dry eye treatments, are described. © 2015 Koh. Source

Kumano G.,Osaka University
Development Growth and Differentiation | Year: 2012

The localization of mRNAs in developing animal cells is essential for establishing cellular polarity and setting up the body plan for subsequent development. Cellular and molecular mechanisms by which maternal mRNAs are localized during oogenesis have been extensively studied in Drosophila and Xenopus. In contrast, evidence for mechanisms used in the localization of mRNAs encoded by developmentally important genes has also been accumulating in several other organisms. This offers the opportunity to unravel the fundamental mechanisms of mRNA localization shared among many species, as well as unique mechanisms specifically acquired or retained by animals based on their developmental needs. In addition to maternal mRNAs, the localization of zygotically expressed mRNAs in the cells of cleaving embryos is also important for early development. In this review, mRNA localization dynamics in the oocytes/eggs of Drosophila and Xenopus are first summarized, and evidence for localized mRNAs in the oocytes/eggs and cleaving embryos of other organisms is then presented. © 2011 The Author. Development, Growth & Differentiation © 2011 Japanese Society of Developmental Biologists. Source

Nakai M.,Osaka University
Plant Cell | Year: 2015

This response to a recent Commentary article by de Vries et al. highlights critical errors in the annotation and identification of Ycf1 homologs in the sequenced chloroplast genomes. Contrary to what is reported by de Vries et al., the majority of chloroplast genomes sequenced to date appear to have retained a typical Ycf1 sequence (i.e., including the N-terminal 6TM domain and a variable hydrophilic C-terminal domain) as my group previously reported. Our evidence continues to support the model that Ycf1 forms an essential component of a “green TIC” that is largely conserved among the Chlorophyta and land plants. Since the establishment of this green TIC with Tic20 as the core component, some cases of loss of Ycf1 during the evolution of the green lineages might be regarded as modifications or alterations of the complex. Here, I discuss our working model that the presence of an alternative “nonphotosynthetic-type” or “ancestral-type” TIC might explain other (or specific) cases of the lack of Ycf1, not only in early lineages, including Glaucophyta and Rhodophyta, but also in the grasses. © 2015 American Society of Plant Biologists. All rights reserved. Source

Monoclonal antibodies (mAbs) that are internalized into cells are a current focus in the development of antibody-drug conjugates (ADCs). We describe a phage display-based high-throughput screening system to rapidly isolate cell-internalizing mAbs. We simultaneously examined the cell-internalizing activities of several hundred independent mAbs and successfully isolated cell-internalizing mAbs against the tumor endothelial markers Roundabout homolog 4 (Robo4) and vascular endothelial growth factor receptor 2 (VEGFR2). Tumor accumulation of mAbs with high cell-internalizing activity was significantly higher than that of mAbs with low cell-internalizing activity. Furthermore, the antitumor effects of ADCs of mAbs with high cell-internalizing activity were significantly stronger than those of mAbs with low cell-internalizing activity. Although anti-VEGFR2 therapy caused a significant loss of body weight, anti-Robo4 therapy did not. These findings indicate that cell-internalizing activity plays an important role in the biodistribution and therapeutic effects of ADCs. Further, Robo4 can be an effective marker for tumor vascular targeting. Source

Arraut I.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

I derive the Komar mass/function for the Schwarszchild-de Sitter black hole inside the de Rham-Gabadadze-Tolley nonlinear theory of massive gravity by taking the usual notion of timelike Killing vector in unitary gauge. The de Rham-Gabadadze-Tolley Komar function depends on the dynamics of the Stückelberg fields through the gauge transformation function. It goes to the standard value obtained in general relativity if the spatial derivative of the gauge function vanishes. In such a case, the (gauge) function corresponds to the usual notion of time as in general relativity. © 2014 American Physical Society. Source

Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed. © 2013 AIP Publishing LLC. Source

Wakamatsu M.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

In recent papers, we have established the existence of gauge-invariant decomposition of nucleon spin, each term of which can be related to known high-energy deep-inelastic-scattering observables. A subtlety remains, however, for the intrinsic spin part of gluons at the quantum level. In fact, it was sometimes claimed that the evolution of gluon spin depends on the gauge choice and its physical interpretation makes sense only in the light-cone gauge. In the present paper, we will demonstrate explicitly that the gluon spin operator appearing in our decomposition evolves gauge-independently and that it properly reproduces the familiar evolution equation for the 1st moments of polarized quark and gluon distributions obtained with the Altarelli-Parisi method, which cannot directly be checked by the standard operator expansion method. © 2011 American Physical Society. Source

Haba N.,Osaka University | Seto O.,Hokkai Gakuen University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We investigate thermal leptogenesis in a supersymmetric neutrinophilic Higgs model by taking phenomenological constraints into account, where, in addition to the minimal supersymmetric standard model, we introduce an extra Higgs field with a tiny vacuum expectation value which generates neutrino masses. Thanks to this tiny vacuum expectation value of the neutrinophilic Higgs, our model allows us to reduce the mass of the lightest right-handed (s)neutrino to be O(105)GeV, keeping sufficiently large CP asymmetry in its decay. Therefore, the reheating temperature after inflation is not necessarily high; hence this scenario is free from the gravitino problem. © 2011 American Physical Society. Source

Hattori K.,Osaka University
Journal of the Physical Society of Japan | Year: 2011

Helical edge states that transport electrons with opposing spins in opposite directions are formed in a quantum spin Hall (QSH) system. These states are essentially robust against time-reversal-invariant perturbations such as nonmagnetic disorder, but are vulnerable to magnetic disorder that breaks time reversal symmetry. In this study, we explore how magnetic disorder affects charge and spin transport in the QSH system on the basis of the nonequilibrium Green's function formalism. We show that quantized charge transport is destroyed by any weak magnetic disorder in an infinitely large system, whereas quantized and conserved spin transport survives magnetic disorder under a specific bias condition as long as the bulk gap remains intact. These two contrasting features are explained in terms of the spinflip backward scattering allowed in helical edge channels and its effects on charge and spin currents. © 2011 The Physical Society of Japan. Source

Van Veen L.,University of Ontario Institute of Technology | Kawahara G.,Osaka University
Physical Review Letters | Year: 2011

Experiments and simulations lend mounting evidence for the edge state hypothesis on subcritical transition to turbulence, which asserts that simple states of fluid motion mediate between laminar and turbulent shear flow as their stable manifolds separate the two in state space. In this Letter we describe flows homoclinic to a time-periodic edge state that display the essential properties of turbulent bursting. During a burst, vortical structures and the associated energy dissipation are highly localized near the wall, in contrast with the familiar regeneration cycle. © 2011 American Physical Society. Source

Takai S.,Osaka University | Kumar R.,Iowa State University
IEEE Transactions on Automatic Control | Year: 2011

For discrete event systems, we study the problem of predicting failures prior to their occurrence, also referred to as prognosis, in the inference-based decentralized framework where multiple decision-makers interact to make the global prognostic decisions. We characterize the class of systems for which there are no missed detections (all failures can be prognosed prior to their occurrence) and no false alarms (all prognostic decisions are correct) by introducing the notion of N -inference-prognosability, where the parameter N represents the maximum ambiguity level of any winning prognostic decision. An algorithm for verifying N-inference-prognosability is presented. We also show that the notion of coprognosability introduced in our prior work is the same as 0-inference-prognosability, and as the parameter N is increased, a larger class of prognosable systems is obtained. © 2010 IEEE. Source

Ohtsuka T.,Osaka University
IEEE Transactions on Automatic Control | Year: 2011

In this paper, the Hamilton-Jacobi equation (HJE) with coefficients consisting of rational functions is considered, and its solutions with algebraic gradients are characterized in terms of commutative algebra. It is shown that there exists a solution with an algebraic gradient if and only if an involutive maximal ideal containing the Hamiltonian exists in a polynomial ring over the rational function field. If such an ideal is found, the gradient of the solution is defined implicitly by a set of algebraic equations. Then, the gradient is determined by solving the set of algebraic equations pointwise without storing the solution over a domain in the state space. Thus, the so-called curse of dimensionality can be removed when a solution to the HJE with an algebraic gradient exists. New classes of explicit solutions for a nonlinear optimal regulator problem are given as applications of the present approach. © 2010 IEEE. Source

Wakamatsu M.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

In a recent paper, we have shown that the way of gauge-invariant decomposition of the nucleon spin is not necessarily unique, but there still exists a preferable decomposition from the observational viewpoint. What was not complete in this argument is a fully satisfactory answer to the following questions. Does the proposed gauge-invariant decomposition, especially the decomposition of the gluon total angular momentum into its spin and orbital parts, correspond to observables which can be extracted from high-energy deep-inelastic-scattering measurements ? Is this decomposition not only gauge invariant but also Lorentz frame independent, so that it is legitimately thought to reflect an intrinsic property of the nucleon? We show that we can answer both of these questions affirmatively by making full use of a gauge-invariant decomposition of the covariant angular-momentum tensor of QCD in an arbitrary Lorentz frame. © 2011 American Physical Society. Source

Shiba N.,Osaka University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We study the entanglement entropy SC of the massless free scalar field on the outside region C of two black holes A and B whose radii are R 1 and R2 and how it depends on the distance r(R 1,R2) between two black holes. If we can consider the entanglement entropy as thermodynamic entropy, we can see the entropic force acting on the two black holes from the r dependence of SC. We develop the computational method based on that of Bombelli et al. to obtain the r dependence of SC of scalar fields whose Lagrangian is quadratic with respect to the scalar fields. First, we study SC in (d+1)-dimensional Minkowski spacetime. In this case the state of the massless free scalar field is the Minkowski vacuum state, and we replace two black holes by two imaginary spheres and take the trace over the degrees of freedom residing in the imaginary spheres. We obtain the leading term of SC with respect to 1/r. The result is SC=SA+SB+1r2d-2G(R 1,R2), where SA and SB are the entanglement entropy on the inside region of A and B, respectively, and G(R 1,R2)≤0. We do not calculate G(R1,R 2) in detail, but we show how to calculate it. In the black hole case we use the method used in the Minkowski spacetime case with some modifications. We show that SC can be expected to be the same form as that in the Minkowski spacetime case. But in the black hole case, SA and S B depend on r, so we do not fully obtain the r dependence of S C. Finally, we assume that the entanglement entropy can be regarded as thermodynamic entropy and consider the entropic force acting on two black holes. We argue how to separate the entanglement entropic force from other forces and how to cancel SA and SB whose r dependences are not obtained. Then we obtain the physical prediction, which can be tested experimentally in principle. © 2011 American Physical Society. Source