Showing papers by "University of Tokyo published in 2000"

The Sloan Digital Sky Survey: Technical summary

Abstract: The Sloan Digital Sky Survey (SDSS) will provide the data to support detailed investigations of the distribution of luminous and nonluminous matter in the universe: a photometrically and astrometrically calibrated digital imaging survey of π sr above about Galactic latitude 30° in five broad optical bands to a depth of g' ~ 23 mag, and a spectroscopic survey of the approximately 106 brightest galaxies and 105 brightest quasars found in the photometric object catalog produced by the imaging survey. This paper summarizes the observational parameters and data products of the SDSS and serves as an introduction to extensive technical on-line documentation.

Titanium dioxide photocatalysis

Abstract: Scientific studies on photocatalysis started about two and a half decades ago. Titanium dioxide (TiO 2 ), which is one of the most basic materials in our daily life, has emerged as an excellent photocatalyst material for environmental purification. In this review, current progress in the area of TiO 2 photocatalysis, mainly photocatalytic air purification, sterilization and cancer therapy are discussed together with some fundamental aspects. A novel photoinduced superhydrophilic phenomenon involving TiO 2 and its applications are presented.

Loop-mediated isothermal amplification of DNA

Abstract: We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem–loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem–loop DNA and a new stem–loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 109 copies of target in less than an hour. The final products are stem–loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.

The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease.

Abstract: ContextAcute aortic dissection is a life-threatening medical emergency associated with high rates of morbidity and mortality. Data are limited regarding the effect of recent imaging and therapeutic advances on patient care and outcomes in this setting.ObjectiveTo assess the presentation, management, and outcomes of acute aortic dissection.DesignCase series with patients enrolled between January 1996 and December 1998. Data were collected at presentation and by physician review of hospital records.SettingThe International Registry of Acute Aortic Dissection, consisting of 12 international referral centers.ParticipantsA total of 464 patients (mean age, 63 years; 65.3% male), 62.3% of whom had type A dissection.Main Outcome MeasuresPresenting history, physical findings, management, and mortality, as assessed by history and physician review of hospital records.ResultsWhile sudden onset of severe sharp pain was the single most common presenting complaint, the clinical presentation was diverse. Classic physical findings such as aortic regurgitation and pulse deficit were noted in only 31.6% and 15.1% of patients, respectively, and initial chest radiograph and electrocardiogram were frequently not helpful (no abnormalities were noted in 12.4% and 31.3% of patients, respectively). Computed tomography was the initial imaging modality used in 61.1%. Overall in-hospital mortality was 27.4%. Mortality of patients with type A dissection managed surgically was 26%; among those not receiving surgery (typically because of advanced age and comorbidity), mortality was 58%. Mortality of patients with type B dissection treated medically was 10.7%. Surgery was performed in 20% of patients with type B dissection; mortality in this group was 31.4%.ConclusionsAcute aortic dissection presents with a wide range of manifestations, and classic findings are often absent. A high clinical index of suspicion is necessary. Despite recent advances, in-hospital mortality rates remain high. Our data support the need for continued improvement in prevention, diagnosis, and management of acute aortic dissection.

Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis

Abstract: A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis.

Orbital Physics in Transition-Metal Oxides

Abstract: An electron in a solid, that is, bound to or nearly localized on the specific atomic site, has three attributes: charge, spin, and orbital. The orbital represents the shape of the electron cloud in solid. In transition-metal oxides with anisotropic-shaped d-orbital electrons, the Coulomb interaction between the electrons (strong electron correlation effect) is of importance for understanding their metal-insulator transitions and properties such as high-temperature superconductivity and colossal magnetoresistance. The orbital degree of freedom occasionally plays an important role in these phenomena, and its correlation and/or order-disorder transition causes a variety of phenomena through strong coupling with charge, spin, and lattice dynamics. An overview is given here on this "orbital physics," which will be a key concept for the science and technology of correlated electrons.

Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

Abstract: In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.

Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution

Abstract: Calcium ATPase is a member of the P-type ATPases that transport ions across the membrane against a concentration gradient. Here we have solved the crystal structure of the calcium ATPase of skeletal muscle sarcoplasmic reticulum (SERCA1a) at 2.6 A resolution with two calcium ions bound in the transmembrane domain, which comprises ten alpha-helices. The two calcium ions are located side by side and are surrounded by four transmembrane helices, two of which are unwound for efficient coordination geometry. The cytoplasmic region consists of three well separated domains, with the phosphorylation site in the central catalytic domain and the adenosine-binding site on another domain. The phosphorylation domain has the same fold as haloacid dehalogenase. Comparison with a low-resolution electron density map of the enzyme in the absence of calcium and with biochemical data suggests that large domain movements take place during active transport.

Plat-E: an efficient and stable system for transient packaging of retroviruses.

Abstract: A potent retrovirus packaging cell line named Platinum-E (Plat-E) was generated based on the 293T cell line. Plat-E is superior to existing packaging cell lines regarding efficiency, stability and safety. The novel packaging constructs utilized in establishment of Plat-E ensure high and stable expression of viral structural proteins. Conventional packaging constructs made use of the promoter of MuLV-LTR for expression of viral structural genes gag-pol and env, while our packaging constructs utilized the EF1alpha promoter, which is 100-fold more potent than the MuLV-LTR in 293T cells in combination with the Kozak's consensus sequence upstream of the initiation codon resulting in high expression of virus structural proteins in Plat-E cells. To maintain the high titers of retroviruses under drug selection pressure, we inserted the IRES (internal ribosome entry site) sequence between the gene encoding gag-pol or env, and the gene encoding a selectable marker in the packaging constructs. Plat-E cells can stably produce retroviruses with an average titer of 1 x 107/ml for at least 4 months. In addition, as we used only the coding sequences of viral structural genes to avoid inclusion of unnecessary retrovirus sequences in the packaging constructs, the probability of generating the replication competent retroviruses (RCR) by recombination can virtually be ruled out.

Review of Particle Physics

Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions., plus 2778 new measurements from 645 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors., probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, top quark, muon anomalous magnetic moment, extra dimensions, particle detectors, cosmic background radiation, dark matter, cosmological parameters, and big bang cosmology.

Kinetically driven quintessence

Abstract: Recently, a novel class of models for inflation has been found in which theinflationary dynamics is driven solely by (non-canonical) kinetic terms ratherthan by potential terms. As an obvious extension, we show that a scalar fieldwith non-canonical kinetic terms alone behaves like an energy componentwhich is time-varying and has negative pressure presently, i.e. quintessence.We present a model which has a constant equation of state, that is, a “kinetic”counterpart of the Ratra-Peebles model of a quintessence field with a potentialterm. We make clear the structure of the phase plane and show that thequintessential solution is a late-time attractor. We also give a model for the“phantom” component which has an equation of state with w = p/ρ < −1.PACS numbers: 98.80.Cq Typeset using REVTEX ∗ Electronic address: chiba@utap.phys.s.u-tokyo.ac.jp, JSPS research fellow. † Electronic address: okabe@utap.phys.s.u-tokyo.ac.jp ‡ Electronic address: gucci@utap.phys.s.u-tokyo.ac.jp, JSPS research fellow.

The DNA sequence of human chromosome 21

Abstract: Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

The Einstein equations on the 3-brane world

Abstract: We carefully investigate the gravitational equations of the brane world, in which all the matter forces except gravity are confined on the 3-brane in a 5-dimensional spacetime with ${Z}_{2}$ symmetry. We derive the effective gravitational equations on the brane, which reduce to the conventional Einstein equations in the low energy limit. From our general argument we conclude that the first Randall-Sundrum-type theory predicts that the brane with a negative tension is an antigravity world and hence should be excluded from the physical point of view. Their second-type theory where the brane has a positive tension provides the correct signature of gravity. In this latter case, if the bulk spacetime is exactly anti--de Sitter spacetime, generically the matter on the brane is required to be spatially homogeneous because of the Bianchi identities. By allowing deviations from anti--de Sitter spacetime in the bulk, the situation will be relaxed and the Bianchi identities give just the relation between the Weyl tensor and the energy momentum tensor. In the present brane world scenario, the effective Einstein equations cease to be valid during an era when the cosmological constant on the brane is not well defined, such as in the case of the matter dominated by the potential energy of the scalar field.

T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma.

Abstract: Bone resorption is regulated by the immune system, where T-cell expression of RANKL (receptor activator of nuclear factor (NF)-kappaB ligand), a member of the tumour-necrosis factor family that is essential for osteoclastogenesis, may contribute to pathological conditions, such as autoimmune arthritis However, whether activated T cells maintain bone homeostasis by counterbalancing the action of RANKL remains unknown Here we show that T-cell production of interferon (IFN)-gamma strongly suppresses osteoclastogenesis by interfering with the RANKL-RANK signalling pathway IFN-gamma induces rapid degradation of the RANK adapter protein, TRAF6 (tumour necrosis factor receptor-associated factor 6), which results in strong inhibition of the RANKL-induced activation of the transcription factor NF-kappaB and JNK This inhibition of osteoclastogenesis is rescued by overexpressing TRAF6 in precursor cells, which indicates that TRAF6 is the target critical for the IFN-gamma action Furthermore, we provide evidence that the accelerated degradation of TRAF6 requires both its ubiquitination, which is initiated by RANKL, and IFN-gamma-induced activation of the ubiquitin-proteasome system Our study shows that there is cross-talk between the tumour necrosis factor and IFN families of cytokines, through which IFN-gamma provides a negative link between T-cell activation and bone resorption Our results may offer a therapeutic approach to treat the inflammation-induced tissue breakdown

Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp. APS.

Abstract: Almost all aphid species (Homoptera, Insecta) have 60-80 huge cells called bacteriocytes, within which are round-shaped bacteria that are designated Buchnera. These bacteria are maternally transmitted to eggs and embryos through host generations, and the mutualism between the host and the bacteria is so obligate that neither can reproduce independently. Buchnera is a close relative of Escherichia coli, but it contains more than 100 genomic copies per cell, and its genome size is only a seventh of that of E. coli. Here we report the complete genome sequence of Buchnera sp. strain APS, which is composed of one 640,681-base-pair chromosome and two small plasmids. There are genes for the biosyntheses of amino acids essential for the hosts in the genome, but those for non-essential amino acids are missing, indicating complementarity and syntrophy between the host and the symbiont. In addition, Buchnera lacks genes for the biosynthesis of cell-surface components, including lipopolysaccharides and phospholipids, regulator genes and genes involved in defence of the cell. These results indicate that Buchnera is completely symbiotic and viable only in its limited niche, the bacteriocyte.

Effects of the Surface Roughness on Sliding Angles of Water Droplets on Superhydrophobic Surfaces

Abstract: Various superhydrophobic films having different surface roughnesses were prepared, and the relationships between the sliding angle, the contact angle, and the surface structure were investigated. In the highly hydrophobic region, the sliding angles of water droplets decreased with increasing contact angles. Microstructural observation revealed that surface structures that can trap air are important for the preparation of low-sliding-angle surfaces. We have also derived an equation that describes the relationship between sliding angles and contact angles on superhydrophobic surfaces with roughness. The results calculated on the basis of this equation agreed well with the experimental ones. Moreover, we have successfully prepared a transparent superhydrophobic film whose sliding angle is ∼1° for a 7 mg water droplet. On this film, there was almost no resistance to the sliding of water droplets. The film obtained satisfies the requirements of superhydrophobicity, transparency, and a low water sliding angle.

AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1

Abstract: The Wnt signalling pathway is essential for development and organogenesis1,2,3. Wnt signalling stabilizes β-catenin, which accumulates in the cytoplasm, binds to T-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes4,5,6. Mutations in CTNNB1 (encoding β-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas7,8,9,10,11,12,13 (HCCs). Because HCCs tend to show accumulation of β-catenin more often than mutations in CTNNB1 , we looked for mutations in AXIN1, encoding a key factor for Wnt signalling, in 6 HCC cell lines and 100 primary HCCs. Among the 4 cell lines and 87 HCCs in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with β-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXIN1 induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated β-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.

Modulation of Akt kinase activity by binding to Hsp90

Abstract: Serine/threonine kinase Akt/PKB is a downstream effector molecule of phosphoinositide 3-kinase and is thought to mediate many biological actions toward anti-apoptotic responses. We found that Akt formed a complex with a 90-kDa heat-shock protein (Hsp90) in vivo. By constructing deletion mutants, we identified that amino acid residues 229–309 of Akt were involved in the binding to Hsp90 and amino acid residues 327–340 of Hsp90β were involved in the binding to Akt. Inhibition of Akt-Hsp90 binding led to the dephosphorylation and inactivation of Akt, which increased sensitivity of the cells to apoptosis-inducing stimulus. The dephosphorylation of Akt was caused by an increase in protein phosphatase 2A (PP2A)-mediated dephosphorylation and not by a decrease in 3-phosphoinositide-dependent protein kinase-1-mediated phosphorylation. These results indicate that Hsp90 plays an important role in maintaining Akt kinase activity by preventing PP2A-mediated dephosphorylation.

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage

Abstract: The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and γ-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.

Potentiometric Selectivity Coefficients of Ion-Selective Electrodes. Part I. Inorganic Cations (Technical Report)

Abstract: Potentiometric selectivity coefficients, K p o t A , B , have been collected for ionophore-based ion-selective electrodes (ISEs) for inorganic cations reported from 1988-1997. In addition to numerical values of K p o t A , B , together with the methods and conditions for their determination response slopes, linear concentration ranges, chemical compositions, and ionophore structures for the ISE membranes are tabulated.

Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition.

Abstract: Alzheimer amyloid beta-peptide (Abeta) is a physiological peptide constantly anabolized and catabolized under normal conditions. We investigated the mechanism of catabolism by tracing multiple-radiolabeled synthetic peptide injected into rat hippocampus. The Abeta1-42 peptide underwent full degradation through limited proteolysis conducted by neutral endopeptidase (NEP) similar or identical to neprilysin as biochemically analyzed. Consistently, NEP inhibitor infusion resulted in both biochemical and pathological deposition of endogenous Abeta42 in brain. This NEP-catalyzed proteolysis therefore limits the rate of Abeta42 catabolism, up-regulation of which could reduce the risk of developing Alzheimer's disease by preventing Abeta accumulation.

Automatic recognition of multi-word terms:. the C-value/NC-value method

Abstract: Technical terms (henceforth called terms ), are important elements for digital libraries. In this paper we present a domain-independent method for the automatic extraction of multi-word terms, from machine-readable special language corpora. The method, (C-value/NC-value ), combines linguistic and statistical information. The first part, C-value, enhances the common statistical measure of frequency of occurrence for term extraction, making it sensitive to a particular type of multi-word terms, the nested terms. The second part, NC-value, gives: 1) a method for the extraction of term context words (words that tend to appear with terms); 2) the incorporation of information from term context words to the extraction of terms.

Toward a protein–protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins

Abstract: tions, constituting '10% of the total to be tested, has revealed 183 independent two-hybrid interactions, more than half of which are entirely novel. Notably, the obtained binary data allow us to extract more complex interaction networks, including the one that may explain a currently unsolved mechanism for the connection between distinct steps of vesicular transport. The approach de- scribed here thus will provide many leads for integration of various cellular functions and serve as a major driving force in the com- pletion of the protein-protein interaction map.

Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer.

Abstract: Tumor cells stimulate the formation of stroma that secretes various mediators pivotal for tumor growth, including growth factors, cytokines, and proteases. However, little is known about the local regulation of these soluble mediators in the human tumor microenvironment. In this study, the local expression of cytokines, chemokines, and angiogenic factors was investigated in primary breast cancer tissue. The concentrations of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-8, macrophage chemoattractant protein (MCP)-1, epithelial-neutrophil activating peptide-78, vascular endothelial growth factor, and thymidine phosphorylase (TP) were measured in 151 primary breast cancer extracts by ELISA. Tumor-associated macrophages (TAMs) were also examined by immunohistochemistry with anti-CD68 antibodies. The correlation between soluble mediators and the relationship between TAM count and soluble mediators were evaluated. MCP-1 concentration was correlated significantly with the level of vascular endothelial growth factor, TP, TNF-alpha, and IL-8, which are potent angiogenic factors. IL-4 concentration was correlated significantly with IL-8 and IL-10. On the other hand, an inverse association was observed between TP and IL-12. The level of MCP-1 was associated significantly with TAM accumulation. In the immunohistochemical analysis, MCP-1 expression was observed in both infiltrating macrophages and tumor cells. Prognostic analysis revealed that high expression of MCP-1, as well as of VEGF, was a significant indicator of early relapse. These findings indicate that interaction between the immune network system and angiogenesis is important for progression of human breast cancer, and that MCP-1 may play an important role in the regulation of angiogenesis and the immune system.