Showing papers by "Kyoto University published in 2014"

Data, information, knowledge and principle: back to metabolism in KEGG

Abstract: In the hierarchy of data, information and knowledge, computational methods play a major role in the initial processing of data to extract information, but they alone become less effective to compile knowledge from information. The Kyoto Encyclopedia of Genes and Genomes (KEGG) resource (http://www.kegg.jp/ or http://www.genome.jp/kegg/) has been developed as a reference knowledge base to assist this latter process. In particular, the KEGG pathway maps are widely used for biological interpretation of genome sequences and other high-throughput data. The link from genomes to pathways is made through the KEGG Orthology system, a collection of manually defined ortholog groups identified by K numbers. To better automate this interpretation process the KEGG modules defined by Boolean expressions of K numbers have been expanded and improved. Once genes in a genome are annotated with K numbers, the KEGG modules can be computationally evaluated revealing metabolic capacities and other phenotypic features. The reaction modules, which represent chemical units of reactions, have been used to analyze design principles of metabolic networks and also to improve the definition of K numbers and associated annotations. For translational bioinformatics, the KEGG MEDICUS resource has been developed by integrating drug labels (package inserts) used in society.

Metal–Organic Frameworks (MOFs)

Abstract: 슈퍼캐패시터(supercapacitor)는 배터리와 함께 많은 양의 전기에너지를 저장 및 공급하 는 중요한 에너지 저장 장치이다. 특히 슈퍼캐 패시터는 고출력이 가능하고 크기와 형태가 조절가능하여 전자기기 부터 자동차 까지 그 사용분야가 매우 넓다 [1-3]. 최근에 웨어러블 (wearable) 디바이스와 플렉서블(flexible) 전 자기기의 발달과 함께 구부릴 수 있고, 당길 수 있는(stretchable) 슈퍼캐패시터의 개발 또한 활발히 진행되고 있다 [4-8]. 슈퍼캐패시터의 작동원리에 따라 전기이중층 캐패시터(electric double-layer capacitor, EDLC)와 의사캐패시터 (pseudocapacitor)로 나뉜다. EDLC는 전하분 리현상을 이용하기 때문에 넓은 표면적을 갖 는 활성탄(activated carbon)과 같은 전극 재료 를 사용하며 의사캐패시터는 전극 재료의 산 화·환원반응(reduction and oxidation, redox) 을 이용하므로 redox반응을 잘 일으키면서 넓 은 표면적을 갖는 전도성 고분자와 금속산화 물 등의 전극 재료를 사용하게된다 [9]. 슈퍼캐 패시터의 전극 재료로서 높은 에너지 저장능 력 및 성능을 갖으려면, 일반적으로 높은 표면 적을 갖도록 해야하며, 슈퍼캐패시터의 성능 은 전극 활물질의 모폴로지(morphology), 기 공크기분포(pore size distribution), 전기전도 도(electrical conductivity), 표면 특성, 열 특성 등의 다양한 성질에 의해 결정되며, 이를 최적 화 했을 때 높은 성능의 슈퍼캐패시터의 제조 가 가능하다 [1]. 일반적으로 다공성 구조의 카 본 및 금속산화물을 만들기 위해서 그 재료의 전구체를 계면활성제(surfactant)를 이용하여 모폴러지 및 다공성을 조절하였다. 계면활성 제의 사용은 다양한 모양과 구조의 활물질제 조를 가능하게 하였지만, 많은 양의 계면활성 제의 사용은 시약의 가격, 후처리, 환경적인 측 면에서 단점을 가진다. 금속유기구조체(metal-organic frameworks, MOFs)는 금속이온과 유기물 연결체(organic linker)로 만들어진 조성물로서, 합성 시 이러한 추가적인 계면활성제의 사용없이 매우 높은 표 면적을 갖는 금속유기 조성물을 만들 수 있다 (그림 1). 이러한 MOF는 사용되는 금속이온, 유 기연결체, 결정구조 등에 따라 MOF-N, HKUSTN, ZIF-N 등 (N: number)으로 구분되어 명명된 다 (그림 1(b)) [10, 11] . 또한, 사용하는 금속이 온과 유기물 연결체의 종류에 따라 다공성 특 성을 조절할 수 있고, 이들의 열처리를 통해서 다공성 카본체 및 금속산화물의 제조가 가능하 다 [12]. 더욱이, MOF는 기존의 다양한 재료에 적용이 가능하여 다양한 에너지저장 재료로 만 들어 질 수 있으며, 나노기술 및 다양한 접근 방 법을 통해 나노구조체 및 조성물의 합성이 가 능하다 [13]. 이러한 장점으로 인해 최근 많은 종류의 MOF 물질들이 슈퍼캐패시터 및 2차전 지의 에너지 저장시스템(energy storage systems, ESSs) 에 응용되고 있다 (그림 2). MOF 중 이미다졸(imidazole) 유도체를 유기연결체로

Physics of Liquid Crystals

Abstract: Over the 100 years since its discovery, liquid crystals have been the intriguing subject for both academia and industries. The textbook of de Gennes The Physics of Liquid Crystals published in 1974 is still the bible for many LC researchers, but new subjects unmentioned in the book have also risen for these years. This chapter describes the story of the recent developments and the future perspectives in physics of liquid crystals, especially focusing on the contributions by Japanese research groups for the last decade.

Scenarios for 5G mobile and wireless communications: the vision of the METIS project

Abstract: METIS is the EU flagship 5G project with the objective of laying the foundation for 5G systems and building consensus prior to standardization. The METIS overall approach toward 5G builds on the evolution of existing technologies complemented by new radio concepts that are designed to meet the new and challenging requirements of use cases today?s radio access networks cannot support. The integration of these new radio concepts, such as massive MIMO, ultra dense networks, moving networks, and device-to-device, ultra reliable, and massive machine communications, will allow 5G to support the expected increase in mobile data volume while broadening the range of application domains that mobile communications can support beyond 2020. In this article, we describe the scenarios identified for the purpose of driving the 5G research direction. Furthermore, we give initial directions for the technology components (e.g., link level components, multinode/multiantenna, multi-RAT, and multi-layer networks and spectrum handling) that will allow the fulfillment of the requirements of the identified 5G scenarios.

Genetics of rheumatoid arthritis contributes to biology and drug discovery

Abstract: A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Photochromism of Diarylethene Molecules and Crystals: Memories, Switches, and Actuators

Abstract: Switches, and Actuators Masahiro Irie,*,† Tuyoshi Fukaminato,‡ Kenji Matsuda, and Seiya Kobatake †Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro 3-34-1, Toshima-ku, Tokyo 171-8501, Japan ‡Research Institute for Electronic Science, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan Department of Applied Chemistry, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan

A chromosome-based draft sequence of the hexaploid bread wheat (Triticum aestivum) genome

Abstract: An ordered draft sequence of the 17-gigabase hexaploid bread wheat (Triticum aestivum) genome has been produced by sequencing isolated chromosome arms. We have annotated 124,201 gene loci distributed nearly evenly across the homeologous chromosomes and subgenomes. Comparative gene analysis of wheat subgenomes and extant diploid and tetraploid wheat relatives showed that high sequence similarity and structural conservation are retained, with limited gene loss, after polyploidization. However, across the genomes there was evidence of dynamic gene gain, loss, and duplication since the divergence of the wheat lineages. A high degree of transcriptional autonomy and no global dominance was found for the subgenomes. These insights into the genome biology of a polyploid crop provide a springboard for faster gene isolation, rapid genetic marker development, and precise breeding to meet the needs of increasing food demand worldwide.

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)

Abstract: OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

Unusual Stability of Acetonitrile-Based Superconcentrated Electrolytes for Fast-Charging Lithium-Ion Batteries

Abstract: The development of a stable, functional electrolyte is urgently required for fast-charging and high-voltage lithium-ion batteries as well as next-generation advanced batteries (e.g., Li–O2 systems). Acetonitrile (AN) solutions are one of the most promising electrolytes with remarkably high chemical and oxidative stability as well as high ionic conductivity, but its low stability against reduction is a critical problem that hinders its extensive applications. Herein, we report enhanced reductive stability of a superconcentrated AN solution (>4 mol dm–3). Applying it to a battery electrolyte, we demonstrate, for the first time, reversible lithium intercalation into a graphite electrode in a reduction-vulnerable AN solvent. Moreover, the reaction kinetics is much faster than in a currently used commercial electrolyte. First-principle calculations combined with spectroscopic analyses reveal that the peculiar reductive stability arises from modified frontier orbital characters unique to such superconcentrated ...

Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies.

Abstract: Summary Background The decision of whether to treat incidental intracranial saccular aneurysms is complicated by limitations in current knowledge of their natural history. We combined individual patient data from prospective cohort studies to determine predictors of aneurysm rupture and to construct a risk prediction chart to estimate 5-year aneurysm rupture risk by risk factor status. Methods We did a systematic review and pooled analysis of individual patient data from 8382 participants in six prospective cohort studies with subarachnoid haemorrhage as outcome. We analysed cumulative rupture rates with Kaplan-Meier curves and assessed predictors with Cox proportional-hazard regression analysis. Findings Rupture occurred in 230 patients during 29 166 person-years of follow-up. The mean observed 1-year risk of aneurysm rupture was 1·4% (95% CI 1·1–1·6) and the 5-year risk was 3·4% (2·9–4·0). Predictors were age, hypertension, history of subarachnoid haemorrhage, aneurysm size, aneurysm location, and geographical region. In study populations from North America and European countries other than Finland, the estimated 5-year absolute risk of aneurysm rupture ranged from 0·25% in individuals younger than 70 years without vascular risk factors with a small-sized ( 20 mm) posterior circulation aneurysm. By comparison with populations from North America and European countries other than Finland, Finnish people had a 3·6-times increased risk of aneurysm rupture and Japanese people a 2·8-times increased risk. Interpretation The PHASES score is an easily applicable aid for prediction of the risk of rupture of incidental intracranial aneurysms. Funding Netherlands Organisation for Health Research and Development.

Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

Abstract: Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing “westernization” or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes.

Structuring of metal–organic frameworks at the mesoscopic/macroscopic scale

Abstract: The assembly of metal ions with organic ligands through the formation of coordination bonds gives crystalline framework materials, known as metal–organic frameworks (MOFs), which recently emerged as a new class of porous materials. Besides the structural designability of MOFs at the molecular length scale, the researchers in this field very recently made important advances in creating more complex architectures at the mesoscopic/macroscopic scale, in which MOF nanocrystals are used as building units to construct higher-order superstructures. The structuring of MOFs in such a hierarchical order certainly opens a new opportunity to improve the material performance via design of the physical form rather than altering the chemical component. This review highlights these superstructures and their applications by categorizing them into four dimensionalities, zero-dimensional (0D), one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) superstructures. Because the key issue for structuring of MOFs is to spatially control the nucleation process in desired locations, this review conceptually categorizes the available synthetic methodologies from the viewpoint of the reaction system.

Photocarrier recombination dynamics in perovskite CH3NH3PbI3 for solar cell applications.

Abstract: Using time-resolved photoluminescence and transient absorption measurements at room temperature, we report excitation-intensity-dependent photocarrier recombination processes in thin films made from the organo-metal halide perovskite semiconductor CH3NH3PbI3 for solar-cell applications. The photocarrier dynamics are well described by a simple rate equation including single-carrier trapping and electron–hole radiative recombination. This result provides clear evidence that the free-carrier model is better than the exciton model for interpreting the optical properties of CH3NH3PbI3. The observed large two-carrier recombination rate suggests the promising potential of perovskite semiconductors for optoelectronic device applications. Our findings provide the information about the dynamical behaviors of photoexcited carriers that is needed for developing high-efficiency perovskite solar cells.

Cellular senescence and its effector programs

Abstract: Cellular senescence is a stress response that accompanies stable exit from the cell cycle. Classically, senescence, particularly in human cells, involves the p53 and p16/Rb pathways, and often both of these tumor suppressor pathways need to be abrogated to bypass senescence. In parallel, a number of effector mechanisms of senescence have been identified and characterized. These studies suggest that senescence is a collective phenotype of these multiple effectors, and their intensity and combination can be different depending on triggers and cell types, conferring a complex and diverse nature to senescence. Series of studies on senescence-associated secretory phenotype (SASP) in particular have revealed various layers of functionality of senescent cells in vivo. Here we discuss some key features of senescence effectors and attempt to functionally link them when it is possible.

Stereospecific PARP Trapping by BMN 673 and Comparison with Olaparib and Rucaparib

Abstract: Anti-poly(ADP-ribose)polymerase (PARP) drugs were initially developed as catalytic inhibitors to block the repair of DNA single-strand breaks. We recently reported that several PARP inhibitors have an additional cytotoxic mechanism by trapping PARP-DNA complexes, and that both olaparib and niraparib act as PARP poisons at pharmacological concentrations. Therefore, we have proposed that PARP inhibitors should be evaluated based both on catalytic PARP inhibition and PARP-DNA trapping. Here, we evaluated the novel PARP inhibitor, BMN 673, and compared its effects on PARP1 and PARP2 with two other clinical PARP inhibitors, olaparib and rucaparib, using biochemical and cellular assays in genetically-modified chicken DT40 and human cancer cell lines. Although BMN 673, olaparib and rucaparib are comparable at inhibiting PARP catalytic activity, BMN 673 is ~100-fold more potent at trapping PARP-DNA complexes and more cytotoxic as single agent than olaparib, while olaparib and rucaparib show similar potencies in trapping PARP-DNA complexes. The high level of resistance of PARP1/2 knockout cells to BMN 673 demonstrates the selectivity of BMN 673 for PARP1/2. Moreover, we show that BMN 673 acts by stereospecific binding to PARP1 as its enantiomer, LT674, is several orders of magnitude less efficient. BMN 673 is also ~100-fold more cytotoxic than olaparib and rucaparib in combination with the DNA alkylating agents methyl methane sufonate (MMS) and temozolomide. Our study demonstrates that BMN 673 is the most potent clinical PARP inhibitor tested to date with the highest efficiency at trapping PARP-DNA complexes.

The evolution of self-control

Abstract: Cognition presents evolutionary research with one of its greatest challenges. Cognitive evolution has been explained at the proximate level by shifts in absolute and relative brain volume and at the ultimate level by differences in social and dietary complexity. However, no study has integrated the experimental and phylogenetic approach at the scale required to rigorously test these explanations. Instead, previous research has largely relied on various measures of brain size as proxies for cognitive abilities. We experimentally evaluated these major evolutionary explanations by quantitatively comparing the cognitive performance of 567 individuals representing 36 species on two problem-solving tasks measuring self-control. Phylogenetic analysis revealed that absolute brain volume best predicted performance across species and accounted for considerably more variance than brain volume controlling for body mass. This result corroborates recent advances in evolutionary neurobiology and illustrates the cognitive consequences of cortical reorganization through increases in brain volume. Within primates, dietary breadth but not social group size was a strong predictor of species differences in self-control. Our results implicate robust evolutionary relationships between dietary breadth, absolute brain volume, and self-control. These findings provide a significant first step toward quantifying the primate cognitive phenome and explaining the process of cognitive evolution.

Negative electrodes for Na-ion batteries.

Abstract: Research interest in Na-ion batteries has increased rapidly because of the environmental friendliness of sodium compared to lithium. Throughout this Perspective paper, we report and review recent scientific advances in the field of negative electrode materials used for Na-ion batteries. This paper sheds light on negative electrode materials for Na-ion batteries: carbonaceous materials, oxides/phosphates (as sodium insertion materials), sodium alloy/compounds and so on. These electrode materials have different reaction mechanisms for electrochemical sodiation/desodiation processes. Moreover, not only sodiation-active materials but also binders, current collectors, electrolytes and electrode/electrolyte interphase and its stabilization are essential for long cycle life Na-ion batteries. This paper also addresses the prospect of Na-ion batteries as low-cost and long-life batteries with relatively high-energy density as their potential competitive edge over the commercialized Li-ion batteries.

Fast Computation of Wasserstein Barycenters

Abstract: We present new algorithms to compute the mean of a set of empirical probability measures under the optimal transport metric. This mean, known as the Wasserstein barycenter, is the measure that minimizes the sum of its Wasserstein distances to each element in that set. We propose two original algorithms to compute Wasserstein barycenters that build upon the subgradient method. A direct implementation of these algorithms is, however, too costly because it would require the repeated resolution of large primal and dual optimal transport problems to compute subgradients. Extending the work of Cuturi (2013), we propose to smooth the Wasserstein distance used in the definition of Wasserstein barycenters with an entropic regularizer and recover in doing so a strictly convex objective whose gradients can be computed for a considerably cheaper computational cost using matrix scaling algorithms. We use these algorithms to visualize a large family of images and to solve a constrained clustering problem.

Sustainable sediment management in reservoirs and regulated rivers: Experiences from five continents

Abstract: By trapping sediment in reservoirs, dams interrupt the continuity of sediment transport through rivers, resulting in loss of reservoir storage and reduced usable life, and depriving downstream reaches of sediments essential for channel form and aquatic habitats. With the acceleration of new dam construction globally, these impacts are increasingly widespread. There are proven techniques to pass sediment through or around reservoirs, to preserve reservoir capacity and to minimize downstream impacts, but they are not applied in many situations where they would be effective. This paper summarizes collective experience from five continents in managing reservoir sediments and mitigating downstream sediment starvation. Where geometry is favorable it is often possible to bypass sediment around the reservoir, which avoids reservoir sedimentation and supplies sediment to downstream reaches with rates and timing similar to pre-dam conditions. Sluicing (or drawdown routing) permits sediment to be transported through the reservoir rapidly to avoid sedimentation during high flows; it requires relatively large capacity outlets. Drawdown flushing involves scouring and re-suspending sediment deposited in the reservoir and transporting it downstream through low-level gates in the dam; it works best in narrow reservoirs with steep longitudinal gradients and with flow velocities maintained above the threshold to transport sediment. Turbidity currents can often be vented through the dam, with the advantage that the reservoir need not be drawn down to pass sediment. In planning dams, we recommend that these sediment management approaches be utilized where possible to sustain reservoir capacity and minimize environmental impacts of dams.

Observation of Electron Neutrino Appearance in a Muon Neutrino Beam

Abstract: The T2K experiment has observed electron neutrino appearance in a muon neutrino beam produced 295 km from the Super-Kamiokande detector with a peak energy of 0.6 GeV. A total of 28 electron neutrino events were detected with an energy distribution consistent with an appearance signal, corresponding to a significance of 7.3 sigma when compared to 4.92 +/- 0.55 expected background events. In the Pontecorvo-Maki-Nakagawa-Sakata mixing model, the electron neutrino appearance signal depends on several parameters including three mixing angles theta(12), theta(23), theta(13), a mass difference vertical bar Delta m(32)(2)vertical bar and a CP violating phase delta(CP). In this neutrino oscillation scenario, assuming vertical bar Delta m(32)(2)vertical bar = 2.4 x 10(-3) eV(2), sin theta(2)(23) = 0.5, and vertical bar Delta m(32)(2)vertical bar > 0 (vertical bar Delta m(32)(2)vertical bar <0), a best- fit value of sin2 theta(2)(13) = 0.140(- 0.032)(+0.038) (0.170(-0.037)(+0.045)) is obtained at delta(CP) = 0. When combining the result with the current best knowledge of oscillation parameters including the world average value of theta(13) from reactor experiments, some values of delta(CP) are disfavored at the 90% C. L.

Iterative Bregman Projections for Regularized Transportation Problems

Abstract: This article details a general numerical framework to approximate so-lutions to linear programs related to optimal transport. The general idea is to introduce an entropic regularization of the initial linear program. This regularized problem corresponds to a Kullback-Leibler Bregman di-vergence projection of a vector (representing some initial joint distribu-tion) on the polytope of constraints. We show that for many problems related to optimal transport, the set of linear constraints can be split in an intersection of a few simple constraints, for which the projections can be computed in closed form. This allows us to make use of iterative Bregman projections (when there are only equality constraints) or more generally Bregman-Dykstra iterations (when inequality constraints are in-volved). We illustrate the usefulness of this approach to several variational problems related to optimal transport: barycenters for the optimal trans-port metric, tomographic reconstruction, multi-marginal optimal trans-port and in particular its application to Brenier's relaxed solutions of in-compressible Euler equations, partial un-balanced optimal transport and optimal transport with capacity constraints.

Extragalactic science, cosmology, and Galactic archaeology with the Subaru Prime Focus Spectrograph

Abstract: The Subaru Prime Focus Spectrograph (PFS) is a massively multiplexed fiber-fed optical and near-infrared three-arm spectrograph (N_fiber = 2400, 380 ≤ λ ≤ 1260 nm, 1 $_{.}^{\circ}$3 diameter field of view). Here, we summarize the science cases in terms of provisional plans for a 300-night Subaru survey. We describe plans to constrain the nature of dark energy via a survey of emission line galaxies spanning a comoving volume of 9.3 h^−3 Gpc^3 in the redshift range 0.8 < z < 2.4. In each of six redshift bins, the cosmological distances will be measured to 3% precision via the baryonic acoustic oscillation scale, and redshift-space distortion measures will constrain structure growth to 6% precision. In the near-field cosmology program, radial velocities and chemical abundances of stars in the Milky Way and M 31 will be used to infer the past assembly histories of spiral galaxies and the structure of their dark matter halos. Data will be secured for 10^6 stars in the Galactic thick-disk, halo, and tidal streams as faint as V ∼ 22, including stars with V < 20 to complement the goals of the Gaia mission. A medium-resolution mode with R = 5000 to be implemented in the red arm will allow the measurement of multiple α-element abundances and more precise velocities for Galactic stars. For the galaxy evolution program, our simulations suggest the wide wavelength range of PFS will be powerful in probing the galaxy population and its clustering over a wide redshift range. We plan to conduct a color-selected survey of 1 < z < 2 galaxies and AGN over 16 deg^2 to J ≃ 23.4, yielding a fair sample of galaxies with stellar masses above ∼10^10 M_⊙ at z ≃ 2. A two-tiered survey of higher redshift Lyman break galaxies and Lyman alpha emitters will quantify the properties of early systems close to the reionization epoch.

Toward the standard population synthesis model of the x-ray background: evolution of x-ray luminosity and absorption functions of active galactic nuclei including compton-thick populations

Abstract: We present the most up-to-date X-ray luminosity function (XLF) and absorption function of Active Galactic Nuclei (AGNs) over the redshift range from 0 to 5, utilizing the largest, highly complete sample ever available obtained from surveys performed with Swift/BAT, MAXI, ASCA, XMM-Newton, Chandra, and ROSAT. The combined sample, including that of the Subaru/XMM-Newton Deep Survey, consists of 4039 detections in the soft (0.5--2 keV) and/or hard ($>2$ keV) band. We utilize a maximum likelihood method to reproduce the count-rate versus redshift distribution for each survey, by taking into account the evolution of the absorbed fraction, the contribution from Compton-thick (CTK) AGNs, and broad band spectra of AGNs including reflection components from tori based on the luminosity and redshift dependent unified scheme. We find that the shape of the XLF at $z \sim 1-3$ is significantly different from that in the local universe, for which the luminosity dependent density evolution model gives much better description than the luminosity and density evolution model. These results establish the standard population synthesis model of the X-Ray Background (XRB), which well reproduces the source counts, the observed fractions of CTK AGNs, and the spectrum of the hard XRB. The number ratio of CTK AGNs to the absorbed Compton-thin (CTN) AGNs is constrained to be $\approx$0.5--1.6 to produce the 20--50 keV XRB intensity within present uncertainties, by assuming that they follow the same evolution as CTN AGNs. The growth history of supermassive black holes is discussed based on the new AGN bolometric luminosity function.

Effects of Extracranial–Intracranial Bypass for Patients With Hemorrhagic Moyamoya Disease: Results of the Japan Adult Moyamoya Trial

Abstract: Background and purpose About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial-intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. Methods This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial-intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Results Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan-Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P=0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148-1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan-Meier survival analysis (2.7%/y versus 7.6%/y; P=0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125-1.009). Conclusions Although statistically marginal, Kaplan-Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. Clinical trial registration url http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000166.

Nonscalable oxidation catalysis of gold clusters.

Abstract: Small, negatively charged gold clusters isolated in vacuum can oxidize CO via electron-transfer-mediated activation of O2. This suggests that Au clusters can act as aerobic oxidation catalysts in the real world when their structure parameters satisfy given required conditions. However, there is a technical challenge for the development of Au cluster oxidation catalysts; the structural parameters of the Au clusters, such as size and composition, must be precisely controlled because the intrinsic chemical properties of the clusters are strongly dependent on these parameters. This Account describes our efforts to achieve precision synthesis of small (diameter <2 nm) Au clusters, stabilized by polymers and immobilized on supports, for a variety of catalytic applications. Since we aim to develop Au cluster catalysts by taking full advantage of their intrinsic, size-specific chemical nature, we chose chemically inert materials for the stabilizers and supports.We began by preparing small Au clusters weakly stabi...

A critical time window for dopamine actions on the structural plasticity of dendritic spines.

Abstract: Animal behaviors are reinforced by subsequent rewards following within a narrow time window. Such reward signals are primarily coded by dopamine, which modulates the synaptic connections of medium spiny neurons in the striatum. The mechanisms of the narrow timing detection, however, remain unknown. Here, we optically stimulated dopaminergic and glutamatergic inputs separately and found that dopamine promoted spine enlargement only during a narrow time window (0.3 to 2 seconds) after the glutamatergic inputs. The temporal contingency was detected by rapid regulation of adenosine 3′,5′-cyclic monophosphate in thin distal dendrites, in which protein-kinase A was activated only within the time window because of a high phosphodiesterase activity. Thus, we describe a molecular basis of reinforcement plasticity at the level of single dendritic spines.

Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial

Abstract: Summary Background Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab. Methods In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy. Eligible patients were randomly assigned (1:1) using a central patient screening and randomisation system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m 2 ) or to placebo plus trastuzumab plus vinorelbine, in 3-week cycles, stratified by previous lapatinib use. The primary endpoint was progression-free survival (PFS) by local assessment in the intention-to-treat population. We report the final analysis for PFS; overall survival follow-up is still in progress. This trial is registered with ClinicalTrials.gov, number NCT01007942. Findings Between Oct 26, 2009, and May 23, 2012, 569 patients were randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at the time of analysis was 20·2 months (IQR 15·0–27·1). Median PFS was 7·00 months (95% CI 6·74–8·18) with everolimus and 5·78 months (5·49–6·90) with placebo (hazard ratio 0·78 [95% CI 0·65–0·95]; p=0·0067). The most common grade 3–4 adverse events were neutropenia (204 [73%] of 280 patients in the everolimus group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%] vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]). Serious adverse events were reported in 117 (42%) patients in the everolimus group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse events occurred in each group. Interpretation The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast cancer. The clinical benefit should be considered in the context of the adverse event profile in this population. Funding Novartis Pharmaceuticals Corporation.