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Showing papers by "Kyoto University published in 2003"


Journal ArticleDOI
14 Feb 2003-Science
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
Abstract: Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naive T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.

8,082 citations


Journal ArticleDOI
John W. Belmont1, Paul Hardenbol, Thomas D. Willis, Fuli Yu1, Huanming Yang2, Lan Yang Ch'Ang, Wei Huang3, Bin Liu2, Yan Shen3, Paul K.H. Tam4, Lap-Chee Tsui4, Mary M.Y. Waye5, Jeffrey Tze Fei Wong6, Changqing Zeng2, Qingrun Zhang2, Mark S. Chee7, Luana Galver7, Semyon Kruglyak7, Sarah S. Murray7, Arnold Oliphant7, Alexandre Montpetit8, Fanny Chagnon8, Vincent Ferretti8, Martin Leboeuf8, Michael S. Phillips8, Andrei Verner8, Shenghui Duan9, Denise L. Lind10, Raymond D. Miller9, John P. Rice9, Nancy L. Saccone9, Patricia Taillon-Miller9, Ming Xiao10, Akihiro Sekine, Koki Sorimachi, Yoichi Tanaka, Tatsuhiko Tsunoda, Eiji Yoshino, David R. Bentley11, Sarah E. Hunt11, Don Powell11, Houcan Zhang12, Ichiro Matsuda13, Yoshimitsu Fukushima14, Darryl Macer15, Eiko Suda15, Charles N. Rotimi16, Clement Adebamowo17, Toyin Aniagwu17, Patricia A. Marshall18, Olayemi Matthew17, Chibuzor Nkwodimmah17, Charmaine D.M. Royal16, Mark Leppert19, Missy Dixon19, Fiona Cunningham20, Ardavan Kanani20, Gudmundur A. Thorisson20, Peter E. Chen21, David J. Cutler21, Carl S. Kashuk21, Peter Donnelly22, Jonathan Marchini22, Gilean McVean22, Simon Myers22, Lon R. Cardon22, Andrew P. Morris22, Bruce S. Weir23, James C. Mullikin24, Michael Feolo24, Mark J. Daly25, Renzong Qiu26, Alastair Kent, Georgia M. Dunston16, Kazuto Kato27, Norio Niikawa28, Jessica Watkin29, Richard A. Gibbs1, Erica Sodergren1, George M. Weinstock1, Richard K. Wilson9, Lucinda Fulton9, Jane Rogers11, Bruce W. Birren25, Hua Han2, Hongguang Wang, Martin Godbout30, John C. Wallenburg8, Paul L'Archevêque, Guy Bellemare, Kazuo Todani, Takashi Fujita, Satoshi Tanaka, Arthur L. Holden, Francis S. Collins24, Lisa D. Brooks24, Jean E. McEwen24, Mark S. Guyer24, Elke Jordan31, Jane Peterson24, Jack Spiegel24, Lawrence M. Sung32, Lynn F. Zacharia24, Karen Kennedy29, Michael Dunn29, Richard Seabrook29, Mark Shillito, Barbara Skene29, John Stewart29, David Valle21, Ellen Wright Clayton33, Lynn B. Jorde19, Aravinda Chakravarti21, Mildred K. Cho34, Troy Duster35, Troy Duster36, Morris W. Foster37, Maria Jasperse38, Bartha Maria Knoppers39, Pui-Yan Kwok10, Julio Licinio40, Jeffrey C. Long41, Pilar N. Ossorio42, Vivian Ota Wang33, Charles N. Rotimi16, Patricia Spallone29, Patricia Spallone43, Sharon F. Terry44, Eric S. Lander25, Eric H. Lai45, Deborah A. Nickerson46, Gonçalo R. Abecasis41, David Altshuler47, Michael Boehnke41, Panos Deloukas11, Julie A. Douglas41, Stacey Gabriel25, Richard R. Hudson48, Thomas J. Hudson8, Leonid Kruglyak49, Yusuke Nakamura50, Robert L. Nussbaum24, Stephen F. Schaffner25, Stephen T. Sherry24, Lincoln Stein20, Toshihiro Tanaka 
18 Dec 2003-Nature
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Abstract: The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

5,926 citations


Journal ArticleDOI
30 Oct 2003-Nature
TL;DR: A silicon-based two-dimensional photonic-crystal slab is used to fabricate a nanocavity with Q = 45,000 and V = 7.0 × 10-14 cm3; the value of Q/V is 10–100 times larger than in previous studies, underlying the realization that light should be confined gently in order to be confined strongly.
Abstract: Photonic cavities that strongly confine light are finding applications in many areas of physics and engineering, including coherent electron-photon interactions, ultra-small filters, low-threshold lasers, photonic chips, nonlinear optics and quantum information processing. Critical for these applications is the realization of a cavity with both high quality factor, Q, and small modal volume, V. The ratio Q/V determines the strength of the various cavity interactions, and an ultra-small cavity enables large-scale integration and single-mode operation for a broad range of wavelengths. However, a high-Q cavity of optical wavelength size is difficult to fabricate, as radiation loss increases in inverse proportion to cavity size. With the exception of a few recent theoretical studies, definitive theories and experiments for creating high-Q nanocavities have not been extensively investigated. Here we use a silicon-based two-dimensional photonic-crystal slab to fabricate a nanocavity with Q = 45,000 and V = 7.0 x 10(-14) cm3; the value of Q/V is 10-100 times larger than in previous studies. Underlying this development is the realization that light should be confined gently in order to be confined strongly. Integration with other photonic elements is straightforward, and a large free spectral range of 100 nm has been demonstrated.

2,715 citations


Journal ArticleDOI
TL;DR: The biomimetic process has been used to deposit nano-sized bone- like apatite on fine polymer fibers, which were textured into a three-dimensional knit framework, which is expected to ultimately lead to bioactive composites that have a bone-like structure and, hence,Bone-like mechanical properties.

1,744 citations


Journal ArticleDOI
TL;DR: In claudin-5–deficient mice, the size-selective loosening of the blood-brain barrier was selectively affected, which provides new insight into the basic molecular physiology of BBB and opens a new way to deliver potential drugs across the BBB into the central nervous system.
Abstract: Tight junctions are well-developed between adjacent endothelial cells of blood vessels in the central nervous system, and play a central role in establishing the blood-brain barrier (BBB). Claudin-5 is a major cell adhesion molecule of tight junctions in brain endothelial cells. To examine its possible involvement in the BBB, claudin-5–deficient mice were generated. In the brains of these mice, the development and morphology of blood vessels were not altered, showing no bleeding or edema. However, tracer experiments and magnetic resonance imaging revealed that in these mice, the BBB against small molecules (<800 D), but not larger molecules, was selectively affected. This unexpected finding (i.e., the size-selective loosening of the BBB) not only provides new insight into the basic molecular physiology of BBB but also opens a new way to deliver potential drugs across the BBB into the central nervous system.

1,617 citations


Journal ArticleDOI
TL;DR: In this paper, a summary and evaluation of the experimental properties of spin-triplet superconductivity in a quasi-two-dimensional Fermi liquid is presented. But the authors do not consider the effect of symmetry-breaking magnetic fields on the phase diagram.
Abstract: This review presents a summary and evaluation of the experimental properties of unconventional superconductivity in ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ as they were known in the spring of 2002. At the same time, the paper is intended to be useful as an introduction to the physics of spin-triplet superconductivity. First, the authors show how the normal-state properties of ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ are quantitatively described in terms of a quasi-two-dimensional Fermi liquid. Then they summarize its phenomenological superconducting parameters in the framework of the Ginzburg-Landau model, and discuss the existing evidence for spin-triplet pairing. After a brief introduction to the vector order parameter, they examine the most likely symmetry of the triplet state. The structure of the superconducting energy gap is discussed, as is the effect of symmetry-breaking magnetic fields on the phase diagram. The article concludes with a discussion of some outstanding issues and desirable future work. Appendixes on additional details of the normal state, difficulty in observing the bulk Fermi surface by angle-resolved photoemission, and the enhancement of superconducting transition temperature in a two-phase ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}\ensuremath{-}\mathrm{Ru}$ system are included.

1,573 citations


Journal ArticleDOI
23 Oct 2003-Nature
TL;DR: A wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathways antagonist.
Abstract: Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.

1,297 citations


Journal ArticleDOI
TL;DR: The origin, allorecognition properties and molecular basis for the suppressive activity of CD4+CD25+ TReg cells, as well as their relationship to other populations of regulatory cells that exist after transplantation, remain a matter of debate.
Abstract: The identification and characterization of regulatory T (T(Reg)) cells that can control immune responsiveness to alloantigens have opened up exciting opportunities for new therapies in transplantation. After exposure to alloantigens in vivo, alloantigen-specific immunoregulatory activity is enriched in a population of CD4+ T cells that express high levels of CD25. In vivo, common mechanisms seem to underpin the activity of CD4+CD25+ T(Reg) cells in both naive and manipulated hosts. However, the origin, allorecognition properties and molecular basis for the suppressive activity of CD4+CD25+ T(Reg) cells, as well as their relationship to other populations of regulatory cells that exist after transplantation, remain a matter of debate..

1,293 citations


Journal ArticleDOI
TL;DR: Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrences, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepaticRecurrence after hepatectomy for HCC.

1,283 citations


Journal ArticleDOI
27 Jun 2003-Science
TL;DR: The use of a polymerizable ionic liquid as the gelling medium allows for the fabrication of a highly electroconductive polymer/nanotube composite material, which showed a substantial enhancement in dynamic hardness.
Abstract: When mixed with imidazolium ion-based room-temperature ionic liquid, pristine single-walled carbon nanotubes formed gels after being ground. The heavily entangled nanotube bundles were found to untangle within the gel to form much finer bundles. Phase transition and rheological properties suggest that the gels are formed by physical cross-linking of the nanotube bundles, mediated by local molecular ordering of the ionic liquids rather than by entanglement of the nanotubes. The gels were thermally stable and did not shrivel, even under reduced pressure resulting from the nonvolatility of the ionic liquids, but they would readily undergo a gel-to-solid transition on absorbent materials. The use of a polymerizable ionic liquid as the gelling medium allows for the fabrication of a highly electroconductive polymer/nanotube composite material, which showed a substantial enhancement in dynamic hardness.

1,258 citations


Journal ArticleDOI
26 Jun 2003-Nature
TL;DR: An atomic model of the closed pore of the nicotinic acetylcholine receptor, obtained by electron microscopy of crystalline postsynaptic membranes, is presented.
Abstract: The nicotinic acetylcholine receptor controls electrical signalling between nerve and muscle cells by opening and closing a gated, membrane-spanning pore. Here we present an atomic model of the closed pore, obtained by electron microscopy of crystalline postsynaptic membranes. The pore is shaped by an inner ring of 5 α-helices, which curve radially to create a tapering path for the ions, and an outer ring of 15 α-helices, which coil around each other and shield the inner ring from the lipids. The gate is a constricting hydrophobic girdle at the middle of the lipid bilayer, formed by weak interactions between neighbouring inner helices. When acetylcholine enters the ligand-binding domain, it triggers rotations of the protein chains on opposite sides of the entrance to the pore. These rotations are communicated through the inner helices, and open the pore by breaking the girdle apart.

Journal ArticleDOI
TL;DR: In this article, the cosmological evolution of the hard X-ray luminosity function (HXLF) of active galactic nuclei (AGNs) in the 2-10 keV luminosity range of 1041.5-1046.5 ergs s-1 was investigated.
Abstract: We investigate the cosmological evolution of the hard X-ray luminosity function (HXLF) of active galactic nuclei (AGNs) in the 2-10 keV luminosity range of 1041.5-1046.5 ergs s-1 as a function of redshift up to 3. From a combination of surveys conducted at photon energies above 2 keV with HEAO 1, ASCA, and Chandra, we construct a highly complete (>96%) sample consisting of 247 AGNs over the wide flux range of 10-10 to 3.8 × 10-15 ergs cm-2 s-1 (2-10 keV). For our purpose, we develop an extensive method of calculating the intrinsic (before absorption) HXLF and the absorption (NH) function. This utilizes the maximum likelihood method, fully correcting for observational biases with consideration of the X-ray spectrum of each source. We find that (1) the fraction of X-ray absorbed AGNs decreases with the intrinsic luminosity and (2) the evolution of the HXLF of all AGNs (including both type I and type II AGNs) is best described with a luminosity-dependent density evolution (LDDE) where the cutoff redshift increases with the luminosity. Our results directly constrain the evolution of AGNs that produce a major part of the hard X-ray background, thus solving its origin quantitatively. A combination of the HXLF and the NH function enables us to construct a purely observation-based population synthesis model. We present basic consequences of this model and discuss the contribution of Compton-thick AGNs to the rest of the hard X-ray background.

Journal ArticleDOI
TL;DR: A map of GFP distribution in the knock‐in mouse brain is constructed and many medium‐sized spherical somata emitting intense GFP fluorescence were observed in layer I, in accord with unidentified GFP‐positive cells.
Abstract: Gamma-aminobutyric acid (GABA)ergic neurons in the central nervous system regulate the activity of other neurons and play a crucial role in information processing. To assist an advance in the research of GABAergic neurons, here we produced two lines of glutamic acid decarboxylase-green fluorescence protein (GAD67-GFP) knock-in mouse. The distribution pattern of GFP-positive somata was the same as that of the GAD67 in situ hybridization signal in the central nervous system. We encountered neither any apparent ectopic GFP expression in GAD67-negative cells nor any apparent lack of GFP expression in GAD67-positive neurons in the two GAD67-GFP knock-in mouse lines. The timing of GFP expression also paralleled that of GAD67 expression. Hence, we constructed a map of GFP distribution in the knock-in mouse brain. Moreover, we used the knock-in mice to investigate the colocalization of GFP with NeuN, calretinin (CR), parvalbumin (PV), and somatostatin (SS) in the frontal motor cortex. The proportion of GFP-positive cells among NeuN-positive cells (neocortical neurons) was approximately 19.5%. All the CR-, PV-, and SS-positive cells appeared positive for GFP. The CR-, PV, and SS-positive cells emitted GFP fluorescence at various intensities characteristics to them. The proportions of CR-, PV-, and SS-positive cells among GFP-positive cells were 13.9%, 40.1%, and 23.4%, respectively. Thus, the three subtypes of GABAergic neurons accounted for 77.4% of the GFP-positive cells. They accounted for 6.5% in layer I. In accord with unidentified GFP-positive cells, many medium-sized spherical somata emitting intense GFP fluorescence were observed in layer I.


Journal ArticleDOI
TL;DR: Michael reaction of malonates to nitrooleolefins with chiral bifunctional organocatalysts, bearing both a thiourea and tertiary amino group, afforded Michael adducts with high yields and enantioselectivities.
Abstract: Michael reaction of malonates to nitroolefins with chiral bifunctional organocatalysts, bearing both a thiourea and tertiary amino group, afforded Michael adducts with high yields and enantioselectivities (up to 95%, up to 93% ee).

Journal ArticleDOI
TL;DR: The authors would like to thank Drs.W.K. van der Klei, Beth Levine, Fulvio Reggiori, and Takahiro Shintani for helpful comments on the manuscript, and the many researchers in the yeast field who have agreed to changes in the standard names of various genes.

Journal ArticleDOI
TL;DR: The data underscore the selective presence of distinct histone lysine methylation states in partitioning chromosomal subdomains but also reveal a surprising plasticity in propagating methylation patterns in eukaryotic chromatin.

Journal ArticleDOI
TL;DR: Periodic nanostructures are observed inside silica glass after irradiation by a focused beam of a femtosecond Ti:sapphire laser, resulting in the periodic modulation of electron plasma concentration and the structural changes in glass.
Abstract: Periodic nanostructures are observed inside silica glass after irradiation by a focused beam of a femtosecond Ti:sapphire laser Backscattering electron images of the irradiated spot reveal a periodic structure of stripelike regions of ~20 nm width with a low oxygen concentration, which are aligned perpendicular to the laser polarization direction These are the smallest embedded structures ever created by light The period of self-organized grating structures can be controlled from ~140 to 320 nm by the pulse energy and the number of irradiated pulses The phenomenon is interpreted in terms of interference between the incident light field and the electric field of the bulk electron plasma wave, resulting in the periodic modulation of electron plasma concentration and the structural changes in glass

Journal ArticleDOI
TL;DR: In this article, the authors investigated the cosmological evolution of the hard X-ray luminosity function (HXLF) of Active Galactic Nuclei (AGN) in the 2-10 keV luminosity range of 10^{41.5} - 10^{46.5] erg s^-1 as a function of redshift up to 3.8*10^{-15} erg cm^-2 s
Abstract: We investigate the cosmological evolution of the hard X-ray luminosity function (HXLF) of Active Galactic Nuclei (AGN) in the 2-10 keV luminosity range of 10^{41.5} - 10^{46.5} erg s^-1 as a function of redshift up to 3. From a combination of surveys conducted at photon energies above 2 keV with HEAO1, ASCA, and Chandra, we construct a highly complete (>96%) sample consisting of 247 AGNs over the wide flux range of 10^{-10} - 3.8*10^{-15} erg cm^-2 s^-1 (2-10 keV). For our purpose, we develop an extensive method of calculating the intrinsic (before-absorption) HXLF and the absorption (N_H) function. This utilizes the maximum likelihood method fully correcting for observational biases with consideration of the X-ray spectrum of each source. We find that (i) the fraction of X-ray absorbed AGNs decreases with the intrinsic luminosity and (ii) the evolution of the HXLF of all AGNs (including both type-I and type-II AGNs) is best described with a luminosity dependent density evolution (LDDE) where the cutoff redshift increases with the luminosity. Our results directly constrain the evolution of AGNs that produce a major part of the hard X-ray background, thus solving its origin quantitatively. A combination of the HXLF and the NH function enables us to construct a purely "observation based" population synthesis model. We present basic consequences of this model, and discuss the contribution of Compton-thick AGNs to the rest of the hard X-ray background.

Journal ArticleDOI
Shigekazu Morito1, H. Tanaka, R. Konishi1, Tadashi Furuhara1, Tadashi Maki1 
TL;DR: In this article, the morphology and crystallography of lath martensite in Fe-C alloys containing various carbon contents from 0.0026 to 0.61% were studied by analyzing electron back scattered diffraction patterns in scanning electron microscopy and Kikuchi diffraction pattern in transmission electron microscope.

Journal ArticleDOI
TL;DR: The results indicate that the r-SBf and i-SBF are less stable than the c- SBF and m-SBFs in terms of changes in ion concentrations relative to storage period.
Abstract: A simulated body fluid (SBF) with ion concentrations approximately equal to those of human blood plasma has been used widely for in vitro assessment of the bioactivity of artificial materials and for the formation of bone-like apatite on various substrates. The ion concentrations of a conventional SBF (c-SBF) are, however, not exactly equal to those of blood plasma. In the present study, a revision of c-SBF was made to prepare new SBFs (r-SBF, i-SBF, and m-SBF) with ion concentrations equal to or closer to those of blood plasma. The ion concentrations of the r-SBF and i-SBF were designed to be equal to those of blood plasma in total and dissociated amounts, respectively. The m-SBF was designed to have a total ion concentration equal to that of blood plasma, except for the concentration of HCO(-) (3), which was set to the saturated level with respect to calcite. The ion concentrations and pH of the as-prepared new SBFs were found to be equal to those of the nominal values. Upon sealed storage, the r-SBF and i-SBF showed no change in ion concentrations for up to 4 weeks at 5 degrees C, and up to 2 weeks at 36.5 degrees C, but thereafter they showed a decrease in HCO(-) (3) concentration and an increase in pH. Under the same storage conditions, the c-SBF and m-SBF showed no change in ion concentrations and pH values over a period of up to 8 weeks. These results indicate that the r-SBF and i-SBF are less stable than the c-SBF and m-SBF in terms of changes in ion concentrations relative to storage period. The m-SBF is optimal for in vitro bioactivity assessment of artificial materials and for biomimetic production of bone-like apatite.

Journal ArticleDOI
TL;DR: In vitro culture of spermatogonial stem cells that proliferate for long periods of time are reported, and gonocytes isolated from neonatal mouse testis proliferated over a 5-month period and restored fertility to congenitally infertile recipient mice following transplantation into seminiferous tubules.
Abstract: Spermatogenesis is a complex process that originates in a small population of spermatogonial stem cells. Here we report the in vitro culture of spermatogonial stem cells that proliferate for long periods of time. In the presence of glial cell line-derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor, gonocytes isolated from neonatal mouse testis proliferated over a 5-month period (>10(14)-fold) and restored fertility to congenitally infertile recipient mice following transplantation into seminiferous tubules. Long-term spermatogonial stem cell culture will be useful for studying spermatogenesis mechanism and has important implications for developing new technology in transgenesis or medicine.


Journal ArticleDOI
TL;DR: It is found that CD25+ CD4+ T cells can proliferate in the absence of added cytokines in culture and in vivo when stimulated by antigen-loaded dendritic cells (DCs), especially mature DCs.
Abstract: An important pathway for immune tolerance is provided by thymic-derived CD25+ CD4+ T cells that suppress other CD25− autoimmune disease–inducing T cells. The antigen-presenting cell (APC) requirements for the control of CD25+ CD4+ suppressor T cells remain to be identified, hampering their study in experimental and clinical situations. CD25+ CD4+ T cells are classically anergic, unable to proliferate in response to mitogenic antibodies to the T cell receptor complex. We now find that CD25+ CD4+ T cells can proliferate in the absence of added cytokines in culture and in vivo when stimulated by antigen-loaded dendritic cells (DCs), especially mature DCs. With high doses of DCs in culture, CD25+ CD4+ and CD25− CD4+ populations initially proliferate to a comparable extent. With current methods, one third of the antigen-reactive T cell receptor transgenic T cells enter into cycle for an average of three divisions in 3 d. The expansion of CD25+ CD4+ T cells stops by day 5, in the absence or presence of exogenous interleukin (IL)-2, whereas CD25− CD4+ T cells continue to grow. CD25+ CD4+ T cell growth requires DC–T cell contact and is partially dependent upon the production of small amounts of IL-2 by the T cells and B7 costimulation by the DCs. After antigen-specific expansion, the CD25+ CD4+ T cells retain their known surface features and actively suppress CD25− CD4+ T cell proliferation to splenic APCs. DCs also can expand CD25+ CD4+ T cells in the absence of specific antigen but in the presence of exogenous IL-2. In vivo, both steady state and mature antigen-processing DCs induce proliferation of adoptively transferred CD25+ CD4+ T cells. The capacity to expand CD25+ CD4+ T cells provides DCs with an additional mechanism to regulate autoimmunity and other immune responses.

Journal ArticleDOI
TL;DR: 1H NMR and static susceptibility measurements have been performed in an organic Mott insulator with a nearly isotropic triangular lattice and suggest that a quantum spin liquid state is realized in the close proximity of the superconducting state appearing under pressure.
Abstract: $^{1}\mathrm{H}$ NMR and static susceptibility measurements have been performed in an organic Mott insulator with a nearly isotropic triangular lattice, $\ensuremath{\kappa}\mathrm{\text{\ensuremath{-}}}(\mathrm{B}\mathrm{E}\mathrm{D}\mathrm{T}\mathrm{\text{\ensuremath{-}}}\mathrm{T}\mathrm{T}\mathrm{F}{)}_{2}{\mathrm{C}\mathrm{u}}_{2}(\mathrm{C}\mathrm{N}{)}_{3}$, which is a model system of frustrated quantum spins. The static susceptibility is described by the spin $S=1/2$ antiferromagnetic triangular-lattice Heisenberg model with the exchange constant $J\ensuremath{\sim}250\text{ }\text{ }\mathrm{K}$. Regardless of the large magnetic interactions, the $^{1}\mathrm{H}$ NMR spectra show no indication of long-range magnetic ordering down to 32 mK, which is 4 orders of magnitude smaller than $J$. These results suggest that a quantum spin liquid state is realized in the close proximity of the superconducting state appearing under pressure.

Journal ArticleDOI
TL;DR: In this article, the structural, magnetic, and electric properties of ferromagnetic perovskite structures were investigated and the changes in the dielectric constant were induced by the magnetic ordering.
Abstract: We have investigated the structural, magnetic, and electric properties of ferromagnetic ${\mathrm{BiMnO}}_{3}$ with a highly distorted perovskite structure. At ${T}_{E}=750--770\mathrm{K},$ a centrosymmetric--to--non-centrosymmetric structural transition takes place, which describes of the ferroelectricity in the system. The changes in the dielectric constant were induced by the magnetic ordering ${(T}_{M}\ensuremath{\approx}100\mathrm{K})$ as well as by the application of magnetic fields near ${T}_{M}.$ These features are attributed to the inherent coupling between the ferroelectric and ferromagnetic orders in the multiferroic system.

Journal ArticleDOI
TL;DR: A new approach for the comprehensive and quantitative analysis of charged metabolites by capillary electrophoresis mass spectrometry (CE-MS) is proposed, which enabled the determination of 352 metabolic standards and its utility was demonstrated in the analysis of 1692 metabolites from Bacillus subtilis extracts.
Abstract: A new approach for the comprehensive and quantitative analysis of charged metabolites by capillary electrophoresis mass spectrometry (CE−MS) is proposed. Metabolites are first separated by CE based...

Journal ArticleDOI
03 Jan 2003-Science
TL;DR: A correlation between geographic distance and cultural difference, a correlation between the abundance of opportunities for social learning and the size of the local cultural repertoire, and no effect of habitat on the content of culture mean that great-ape cultures exist and may have done so for at least 14 million years.
Abstract: Geographic variation in some aspects of chimpanzee behavior has been interpreted as evidence for culture Here we document similar geographic variation in orangutan behaviors Moreover, as expected under a cultural interpretation, we find a correlation between geographic distance and cultural difference, a correlation between the abundance of opportunities for social learning and the size of the local cultural repertoire, and no effect of habitat on the content of culture Hence, great-ape cultures exist, and may have done so for at least 14 million years

Journal ArticleDOI
31 Jan 2003-Science
TL;DR: The structure of Escherichia colisuccinate dehydrogenase (SQR), analogous to the mitochondrial respiratory complex II, has been determined, revealing the electron transport pathway from the electron donor, succinate, to the terminal electron acceptor, ubiquinone.
Abstract: The structure of Escherichia coli succinate dehydrogenase (SQR), analogous to the mitochondrial respiratory complex II, has been determined, revealing the electron transport pathway from the electron donor, succinate, to the terminal electron acceptor, ubiquinone It was found that the SQR redox centers are arranged in a manner that aids the prevention of reactive oxygen species (ROS) formation at the flavin adenine dinucleotide This is likely to be the main reason SQR is expressed during aerobic respiration rather than the related enzyme fumarate reductase, which produces high levels of ROS Furthermore, symptoms of genetic disorders associated with mitochondrial SQR mutations may be a result of ROS formation resulting from impaired electron transport in the enzyme

Journal ArticleDOI
TL;DR: In this article, the kinematic constitutive equation for the drift velocity has been studied for various two-phase flow regimes, and a comparison of the model with various experimental data over various flow regimes and a wide range of flow parameters shows a satisfactory agreement.