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Showing papers by "Kyoto University published in 2012"


Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2964 moreInstitutions (200)
TL;DR: In this article, a search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9.

9,282 citations


Journal ArticleDOI
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

4,316 citations


Journal ArticleDOI
TL;DR: KEGG Mapper, a collection of tools for KEGG PATHWAY, BRITE and MODULE mapping, enabling integration and interpretation of large-scale data sets and recent enhancements to the K EGG content, especially the incorporation of disease and drug information used in practice and in society, to support translational bioinformatics.
Abstract: Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp/kegg/ or http://www.kegg.jp/) is a database resource that integrates genomic, chemical and systemic functional information. In particular, gene catalogs from completely sequenced genomes are linked to higher-level systemic functions of the cell, the organism and the ecosystem. Major efforts have been undertaken to manually create a knowledge base for such systemic functions by capturing and organizing experimental knowledge in computable forms; namely, in the forms of KEGG pathway maps, BRITE functional hierarchies and KEGG modules. Continuous efforts have also been made to develop and improve the cross-species annotation procedure for linking genomes to the molecular networks through the KEGG Orthology system. Here we report KEGG Mapper, a collection of tools for KEGG PATHWAY, BRITE and MODULE mapping, enabling integration and interpretation of large-scale data sets. We also report a variant of the KEGG mapping procedure to extend the knowledge base, where different types of data and knowledge, such as disease genes and drug targets, are integrated as part of the KEGG molecular networks. Finally, we describe recent enhancements to the KEGG content, especially the incorporation of disease and drug information used in practice and in society, to support translational bioinformatics.

4,259 citations


Journal ArticleDOI
TL;DR: In this article, Advanced Camera for Surveys, NICMOS and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey was presented.
Abstract: We present Advanced Camera for Surveys, NICMOS, and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on board HST. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Union.

1,784 citations


Journal ArticleDOI
TL;DR: The English version of the JSCCR Guidelines 2016 is presented, which can be used as a tool for treating colorectal cancer in actual clinical practice settings and as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient.
Abstract: Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms in women and the third largest number in men. Many new treatment methods have been developed over the last few decades. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer (JSCCR Guidelines 2010) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2010.

1,709 citations


Journal ArticleDOI
P. L. Nolan1, A. A. Abdo2, A. A. Abdo3, Markus Ackermann  +290 moreInstitutions (53)
TL;DR: The second Fermi-LAT catalog (2FGL) as mentioned in this paper includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms either power-law, exponentially cutoff power law, or log-normal forms.
Abstract: We present the second catalog of high-energy γ-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), derived from data taken during the first 24 months of the science phase of the mission, which began on 2008 August 4. Source detection is based on the average flux over the 24 month period. The second Fermi-LAT catalog (2FGL) includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms of power-law, exponentially cutoff power-law, or log-normal forms. Also included are flux measurements in five energy bands and light curves on monthly intervals for each source. Twelve sources in the catalog are modeled as spatially extended. We provide a detailed comparison of the results from this catalog with those from the first Fermi-LAT catalog (1FGL). Although the diffuse Galactic and isotropic models used in the 2FGL analysis are improved compared to the 1FGL catalog, we attach caution flags to 162 of the sources to indicate possible confusion with residual imperfections in the diffuse model. The 2FGL catalog contains 1873 sources detected and characterized in the 100 MeV to 100 GeV range of which we consider 127 as being firmly identified and 1171 as being reliably associated with counterparts of known or likely γ-ray-producing source classes.

1,541 citations


Journal ArticleDOI
TL;DR: The comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists and have increased the sensitivity of diagnosis to 100% for Igg4-related MD, KD, and AIP.
Abstract: IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz’s disease (MD) and kidney disease (KD) In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists

1,417 citations


Journal ArticleDOI
TL;DR: It is demonstrated that an optic cup structure can form by self-organization in human ESC culture and an optimized vitrification method enables en bloc cryopreservation of stratified neural retina of human origin.

1,200 citations


Journal ArticleDOI
TL;DR: The results showed that the new intracellular thermometry could determine an intrinsic relationship between the temperature and organelle function, and not just the spatial and temperature resolutions.
Abstract: Intracellular temperature mapping has not previously been achieved. Now, a fluorescent polymeric thermometer has been developed that can be used in combination with fluorescence-lifetime imaging microscopy to allow thermometry with spatial and temperature resolutions of 200 nm and 0.18–0.58 ° C.

951 citations




Journal ArticleDOI
TL;DR: Findings show that preinvasion perception of plant-derived signals substantially reprograms fungal gene expression and indicate previously unknown functions for particular fungal cell types.
Abstract: Colletotrichum species are fungal pathogens that devastate crop plants worldwide. Host infection involves the differentiation of specialized cell types that are associated with penetration, growth inside living host cells (biotrophy) and tissue destruction (necrotrophy). We report here genome and transcriptome analyses of Colletotrichum higginsianum infecting Arabidopsis thaliana and Colletotrichum graminicola infecting maize. Comparative genomics showed that both fungi have large sets of pathogenicity-related genes, but families of genes encoding secreted effectors, pectin-degrading enzymes, secondary metabolism enzymes, transporters and peptidases are expanded in C. higginsianum. Genome-wide expression profiling revealed that these genes are transcribed in successive waves that are linked to pathogenic transitions: effectors and secondary metabolism enzymes are induced before penetration and during biotrophy, whereas most hydrolases and transporters are upregulated later, at the switch to necrotrophy. Our findings show that preinvasion perception of plant-derived signals substantially reprograms fungal gene expression and indicate previously unknown functions for particular fungal cell types.

Journal ArticleDOI
Shinya Yamanaka1
TL;DR: The development of iPSCs reflected the merging of three major scientific streams and has in turn led to additional new branches of investigation, but there is still debate about whetheriPSCs are functionally equivalent to ESCs.

Journal ArticleDOI
23 Feb 2012-Nature
TL;DR: The structure of the antagonist-bound human M2 receptor is reported, the first human acetylcholine receptor to be characterized structurally, to the authors' knowledge, and provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.
Abstract: The X-ray crystal structure of the M2 muscarinic acetylcholine receptor, which is essential for the physiological control of cardiovascular function, is reported. The muscarinic acetylcholine receptors (mAChRs) constitute a family of G-protein-coupled receptors. These membrane proteins are targets for treatment of a broad range of conditions, including Alzheimer's disease, schizophrenia and chronic obstructive pulmonary disease. The five mAChR subtypes (M1–M5) share a high degree of sequence homology, but show marked differences in G-protein-coupling preference and physiological function. This pair of papers from Brian Kobilka's group presents the structures of two of the five subtypes. Haga et al. report the X-ray crystal structure of the M2 receptor, which is essential for the physiological control of cardiovascular function; Kruse et al. determine the structure of the M3 receptor, active in the bronchial airways and elsewhere. Comparison of the two structures reveals key differences that could potentially be exploited to develop subtype-selective drugs. The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves1,2,3,4,5. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.

Journal ArticleDOI
12 Jul 2012-PLOS ONE
TL;DR: New ITS primers with improved coverage across diverse taxonomic groups of fungi compared to existing primers are designed to provide a basis for ecological studies on the diversity and community structures of fungi in the era of massive DNA sequencing.
Abstract: The kingdom Fungi is estimated to include 1.5 million or more species, playing key roles as decomposers, mutualists, and parasites in every biome on the earth. To comprehensively understand the diversity and ecology of this huge kingdom, DNA barcoding targeting the internal transcribed spacer (ITS) region of the nuclear ribosomal repeat has been regarded as a prerequisite procedure. By extensively surveying ITS sequences in public databases, we designed new ITS primers with improved coverage across diverse taxonomic groups of fungi compared to existing primers. An in silico analysis based on public sequence databases indicated that the newly designed primers matched 99% of ascomycete and basidiomycete ITS taxa (species, subspecies or varieties), causing little taxonomic bias toward either fungal group. Two of the newly designed primers could inhibit the amplification of plant sequences and would enable the selective investigation of fungal communities in mycorrhizal associations, soil, and other types of environmental samples. Optimal PCR conditions for the primers were explored in an in vitro investigation. The new primers developed in this study will provide a basis for ecological studies on the diversity and community structures of fungi in the era of massive DNA sequencing.

Journal ArticleDOI
TL;DR: Although IgG4RD forms a distinct, clinically independent disease category and is attracting strong attention as a new clinical entity, many questions and problems still remain to be elucidated, including its pathogenesis, the establishment of diagnostic criteria, and the role of IgG 4.
Abstract: IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz’s disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor. Although IgG4RD forms a distinct, clinically independent disease category and is attracting strong attention as a new clinical entity, many questions and problems still remain to be elucidated, including its pathogenesis, the establishment of diagnostic criteria, and the role of IgG4. Here we describe the concept of IgG4RD and up-to-date information on this emerging disease entity.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, W. B. Atwood2, Luca Baldini3  +176 moreInstitutions (36)
TL;DR: In this paper, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmicray confinement volume (halo), and distribution of interstellar gas.
Abstract: The gamma-ray sky >100 MeV is dominated by the diffuse emissions from interactions of cosmic rays with the interstellar gas and radiation fields of the Milky Way. Observations of these diffuse emissions provide a tool to study cosmic-ray origin and propagation, and the interstellar medium. We present measurements from the first 21 months of the Fermi-LAT mission and compare with models of the diffuse gamma-ray emission generated using the GALPROP code. The models are fitted to cosmic-ray data and incorporate astrophysical input for the distribution of cosmic-ray sources, interstellar gas and radiation fields. To assess uncertainties associated with the astrophysical input, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmic-ray confinement volume (halo), and the distribution of interstellar gas. An all-sky maximum-likelihood fit is used to determine the Xco-factor, the ratio between integrated CO-line intensity and molecular hydrogen column density, the fluxes and spectra of the gamma-ray point sources from the first Fermi-LAT catalogue, and the intensity and spectrum of the isotropic background including residual cosmic rays that were misclassified as gamma rays, all of which have some dependency on the assumed diffuse emission model. The models are compared on the basis of their maximum likelihood ratios as well as spectra, longitude, and latitude profiles. We also provide residual maps for the data following subtraction of the diffuse emission models. The models are consistent with the data at high and intermediate latitudes but under-predict the data in the inner Galaxy for energies above a few GeV. Possible explanations for this discrepancy are discussed, including the contribution by undetected point source populations and spectral variations of cosmic rays throughout the Galaxy.

Journal ArticleDOI
Markus Ackermann1, Marco Ajello1, Alice Allafort1, W. B. Atwood2  +155 moreInstitutions (31)
TL;DR: The Fermi Large Area Telescope measured separate cosmic-ray electron and positron spectra to distinguish the two species by exploiting Earth's shadow, and it is confirmed that the fraction rises with energy in the 20-100 GeV range.
Abstract: We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting the Earth's shadow, which is offset in opposite directions for opposite charges due to the Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 GeV and 200 GeV. We confirm that the fraction rises with energy in the 20--100 GeV range and determine for the first time that it continues to rise between 100 and 200 GeV.

Journal ArticleDOI
16 Nov 2012-Science
TL;DR: It is shown that female (XX) embryonic stem cells and induced pluripotent stem cells in mice are induced into primordial germ cell–like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, undergo X-reactivation, imprint erasure, and cyst formation, and exhibit meiotic potential.
Abstract: In mice, male embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to differentiate into primordial germ cell–like cells (PGCLCs) in vitro. Upon transplantation into testes, these PGCLCs can form fully functional sperm. Again working in mice, Hayashi et al. (p. [971][1], published online 4 October) found that female ESCs and iPSCs can also differentiate into PGCLCs, which, when aggregated in reconstituted ovaries, exhibited epigenetic reprogramming and meiotic potential in vitro. Upon transplantation of the reconstituted ovaries under ovarian bursa, female PGCLCs developed into fully grown oocytes that contributed to healthy offspring upon in vitro maturation and fertilization. [1]: /lookup/volpage/338/971

Journal ArticleDOI
16 Nov 2012-Immunity
TL;DR: It is shown that Treg cell development was achieved by the combination of two independent processes, i.e., the expression of Foxp3 and the establishment of TReg cell-specific CpG hypomethylation pattern, and those T cells in which the two events have concurrently occurred are developmentally set into the T Reg cell lineage.

Journal ArticleDOI
TL;DR: The systematic evolution of the electronic structure and comprehensive analysis of steady-state and transient PL along with photoluminescence excitation (PLE) spectroscopy measurements indicate that two different types of electronically excited states are responsible for the observed emission characteristics.
Abstract: Graphene oxide (GO) is a graphene sheet modified with oxygen functional groups in the form of epoxy and hydroxy groups on the basal plane and various other types at the edges. It exhibits interesting steady-state photoluminescence (PL) properties. For example, low-energy fluorescence in red to near infrared (NIR) wavelengths (from 600– 1100 nm) has been detected for suspensions and solid thin films of as-synthesized GO. 3] In addition, broad luminescence from 400 to 800 nm from oxygen plasma-treated, mechanically exfoliated, single-layer graphene sheet has been reported. Blue fluorescence with a relatively narrow bandwidth when excited with UV irradiation has also been detected from chemically reduced GO (rGO) and graphene quantum dots. 6] Recently, chemically modified GO or rGO with n-butylamine or Mn has also demonstrated PL emission at a range of energies. 10] A detailed explanation of the origin of such variable energy PL in GO has yet to be elucidated. This is partly because the sample preparation and reduction methods varied, making it difficult to compare the results. Herein, we have prepared GO suspensions that exhibit virtually all of the PL features observed by different groups, through careful and gradual reduction of the GO. The systematic evolution of the electronic structure and comprehensive analysis of steady-state and transient PL along with photoluminescence excitation (PLE) spectroscopy measurements indicate that two different types of electronically excited states are responsible for the observed emission characteristics. GO was synthesized using the modified Hummers method, the details of which have been reported. GO usually contains a large fraction of sp hybridized carbon atoms bound to oxygen functional groups, which makes it an insulator. Reduction can be achieved chemically (e.g. hydrazine exposure) or by thermal annealing in inert environments. Photothermal reduction of GO can be achieved by exposing GO samples to a Xenon flash in ambient conditions. In this study, we prepared aqueous GO solutions and subjected them to steady-state Xe lamp irradiation (500 W) with different exposure times of up to three hours. In contrast to reduction by an instantaneous flash, this method provides a controllable, gradual transformation from GO to rGO, allowing exploration of the PL evolution and emission mechanisms from as-synthesized GO to rGO. The deoxygenation of GO after reduction was confirmed by X-ray photoelectron spectroscopy (XPS), as shown in Figure 1. The C 1s signals of the original GO can be deconvoluted into signals for the C=C bond in aromatic rings (284.6 eV), C O bond (286.1 eV), C=O bond (287.5 eV), and C(=O) OH bond (289.2 eV), in agreement with previous assignments. Increased sp carbon bonding with increased reduction time can be clearly measured, which

Journal ArticleDOI
15 Mar 2012-Nature
TL;DR: This study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
Abstract: Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.

Journal ArticleDOI
TL;DR: Nanoporous carbon shows much higher porosity than other carbon materials (such as activated carbons and mesoporous carbons) and exhibits superior sensing capabilities toward toxic aromatic substances.
Abstract: Nanoporous carbon (NPC) is prepared by direct carbonization of Al-based porous coordination polymers (Al-PCP). By applying the appropriate carbonization temperature, both high surface area and large pore volume are realized for the first time. Our NPC shows much higher porosity than other carbon materials (such as activated carbons and mesoporous carbons). This new type of carbon material exhibits superior sensing capabilities toward toxic aromatic substances.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek  +3081 moreInstitutions (197)
TL;DR: A combined search for the Standard Model Higgs boson with the ATLAS experiment at the LHC using datasets corresponding to integrated luminosities from 1.04 fb(-1) to 4.9 fb(1) of pp collisions is described in this paper.

Journal ArticleDOI
TL;DR: The 2012 plasma road map as mentioned in this paper provides guidance to the field by reviewing the major challenges of low-temperature plasma physics and their many sub-fields, as well as a review of the current state of the art in the field.
Abstract: Low-temperature plasma physics and technology are diverse and interdisciplinary fields. The plasma parameters can span many orders of magnitude and applications are found in quite different areas of daily life and industrial production. As a consequence, the trends in research, science and technology are difficult to follow and it is not easy to identify the major challenges of the field and their many sub-fields. Even for experts the road to the future is sometimes lost in the mist. Journal of Physics D: Applied Physics is addressing this need for clarity and thus providing guidance to the field by this special Review article, The 2012 Plasma Roadmap.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, Andrea Albert2, Alice Allafort1  +220 moreInstitutions (42)
TL;DR: The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the FermI Gamma-ray Space Telescope (fermi) mission, is an imaging, wide field-of-view, high-energy \gamma-ray telescope, covering the energy range from 20 MeV to more than 300 GeV as discussed by the authors.
Abstract: The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy \gamma-ray telescope, covering the energy range from 20 MeV to more than 300 GeV. During the first years of the mission the LAT team has gained considerable insight into the in-flight performance of the instrument. Accordingly, we have updated the analysis used to reduce LAT data for public release as well as the Instrument Response Functions (IRFs), the description of the instrument performance provided for data analysis. In this paper we describe the effects that motivated these updates. Furthermore, we discuss how we originally derived IRFs from Monte Carlo simulations and later corrected those IRFs for discrepancies observed between flight and simulated data. We also give details of the validations performed using flight data and quantify the residual uncertainties in the IRFs. Finally, we describe techniques the LAT team has developed to propagate those uncertainties into estimates of the systematic errors on common measurements such as fluxes and spectra of astrophysical sources.

Journal ArticleDOI
24 May 2012-Nature
TL;DR: Maehara et al. as discussed by the authors reported observations of 365 superflares, including some from slowly rotating solar-type stars, from about 83,000 stars observed over 120 days.
Abstract: Observations of superflares on solar-type stars indicate that they are associated with much larger starspots than appear on the Sun, occur more frequently on rapidly rotating stars and, contrary to a previous proposal, are not frequently associated with hot Jupiters. Solar flares are the most energetic explosions in the solar atmosphere, and similar flares occur on many stars. 'Superflares' many thousands of times more energetic than the average solar flare have been observed from a variety of stars, but the relatively small number observed on solar-type stars has hitherto precluded a detailed study of them. Now, on the basis of an analysis of data from the Kepler satellite, Maehara et al. report observations of 365 superflares, including 101 from slowly rotating solar-type stars, from a sample of around 83,000 stars observed over 120 days. The data suggest that superflares occur more frequently on rapidly rotating stars and on stars with 'starspots' much larger than the sunspots with which we are familiar. There is no historical record of superflares on the Sun in the past 2,000 years, and it is probable that none has occurred in the past one billion years. Bradley Schaefer discusses these findings in an accompanying News and Views, and concludes that it is extremely unlikely that the Sun will host a superflare. Solar flares are caused by the sudden release of magnetic energy stored near sunspots. They release 1029 to 1032 ergs of energy on a timescale of hours1. Similar flares have been observed on many stars, with larger ‘superflares’ seen on a variety of stars2,3, some of which are rapidly rotating4,5 and some of which are of ordinary solar type3,6. The small number of superflares observed on solar-type stars has hitherto precluded a detailed study of them. Here we report observations of 365 superflares, including some from slowly rotating solar-type stars, from about 83,000 stars observed over 120 days. Quasi-periodic brightness modulations observed in the solar-type stars suggest that they have much larger starspots than does the Sun. The maximum energy of the flare is not correlated with the stellar rotation period, but the data suggest that superflares occur more frequently on rapidly rotating stars. It has been proposed that hot Jupiters may be important in the generation of superflares on solar-type stars7, but none have been discovered around the stars that we have studied, indicating that hot Jupiters associated with superflares are rare.

Journal ArticleDOI
TL;DR: It is suggested that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features, and formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the results of laboratory experiments that have provided initial constraints on the nuclear symmetry energy and on its density dependence at and somewhat below normal nuclear matter density.
Abstract: The symmetry energy contribution to the nuclear equation of state impacts various phenomena in nuclear astrophysics, nuclear structure, and nuclear reactions. Its determination is a key objective of contemporary nuclear physics, with consequences for the understanding of dense matter within neutron stars. We examine the results of laboratory experiments that have provided initial constraints on the nuclear symmetry energy and on its density dependence at and somewhat below normal nuclear matter density. Even though some of these constraints have been derived from properties of nuclei while others have been derived from the nuclear response to electroweak and hadronic probes, within experimental uncertainties-they are consistent with each other. We also examine the most frequently used theoretical models that predict the symmetry energy and its slope parameter. By comparing existing constraints on the symmetry pressure to theories, we demonstrate how contributions of three-body forces, which are essential ingredients in neutron matter models, can be determined.

Journal ArticleDOI
TL;DR: The new work provides an encouraging step toward using motor neurons generated from iPSCs derived from ALS patients to learn more about what triggers the death of motor neurons in this disease and to identify new candidate drugs that may be able to slow or reverse the devastating loss ofMotor neurons.
Abstract: Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which the motor neurons degenerate. The discovery of new drugs for treating ALS has been hampered by a lack of access to motor neurons from ALS patients and appropriate disease models. We generate motor neurons from induced pluripotent stem cells (iPSCs) from familial ALS patients, who carry mutations in Tar DNA binding protein-43 (TDP-43). ALS patient–specific iPSC–derived motor neurons formed cytosolic aggregates similar to those seen in postmortem tissue from ALS patients and exhibited shorter neurites as seen in a zebrafish model of ALS. The ALS motor neurons were characterized by increased mutant TDP-43 protein in a detergent-insoluble form bound to a spliceosomal factor SNRPB2. Expression array analyses detected small increases in the expression of genes involved in RNA metabolism and decreases in the expression of genes encoding cytoskeletal proteins. We examined four chemical compounds and found that a histone acetyltransferase inhibitor called anacardic acid rescued the abnormal ALS motor neuron phenotype. These findings suggest that motor neurons generated from ALS patient–derived iPSCs may provide a useful tool for elucidating ALS disease pathogenesis and for screening drug candidates.