ALBERT

Description: Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. More than 90% of patients with SSc are positive for autoantibodies. In addition, serum B cell activating factor (BAFF) level is correlated with SSc severity and activity. Thus, B cells are considered to play a pathogenic role in SSc. However, there are two opposing subsets: regulatory B cells (Bregs) and effector B cells (Beffs). Interleukin-10 (IL-10)–producing Bregs negatively regulate the immune response, while IL-6–producing Beffs positively regulate it. Therefore, a protocol that selectively depletes Beffs would represent a potent therapy for SSc. The aims of this study were to investigate the roles of Bregs and Beffs in SSc and to provide a scientific basis for developing a new treatment strategy targeting B cells. A bleomycin-induced scleroderma model was induced in mice with a B cell–specific deficiency in IL-6 or IL-10. We also examined whether BAFF regulates cytokine-producing B cells and its effects on the scleroderma model. IL-6–producing Beffs increased in number and infiltrated the inflamed skin in the scleroderma model. The skin and lung fibrosis was attenuated in B cell–specific IL-6–deficient mice, whereas B cell–specific IL-10–deficient mice showed more severe fibrosis. In addition, BAFF increased Beffs but suppressed Bregs. Furthermore, BAFF antagonist attenuated skin and lung fibrosis in the scleroderma model with reduction of Beffs but not of Bregs. The current study indicates that Beffs play a pathogenic role in the scleroderma model, while Bregs play a protective role. BAFF inhibition is a potential therapeutic strategy for SSc via alteration of B cell balance.

Description: Author(s): Y. Matsuda, H. Sakaguchi, H. Takeda, S. Terashima, J. Zenihiro, T. Kobayashi, T. Murakami, Y. Iwao, T. Ichihara, T. Suda, T. Ohnishi, Y. Watanabe, H. Otsu, K. Yoneda, Y. Satou, K. Ozeki, and M. Kanazawa The angular distribution of proton- 9 C elastic scattering at 277–300 MeV/nucleon was measured with a newly designed recoil proton spectrometer. The angular distribution was analyzed using the relativistic impulse approximation. The root-mean-square matter radius of 9 C was deduced to be 2.43 −0.28 +0.55 ... [Phys. Rev. C 87, 034614] Published Tue Mar 12, 2013

Description: We report the first finding of diamond and moissanite in metasedimentary crustal rocks of Pohorje Mountains (Slovenia) in the Austroalpine ultrahigh-pressure metamorphic terrane of the Eastern Alps. Microscopic observations and Raman spectroscopy show that diamond occurs in situ as inclusions in garnet, being heterogeneously distributed. Under the optical microscope, diamond–bearing inclusions are of cuboidal to rounded shape and of pinkish, yellow to brownish colour. The Raman spectra of the investigated diamond show a sharp, first order peak of sp 3 -bonded carbon, in most cases centred between 1332 and 1330 cm -1 , with a full width at half maximum (FWHM) between 3 and 5 cm -1 . Several spectra show Raman bands typical for disordered graphitic (sp 2 -bonded) carbon. Detailed observations show that diamond occurs either as a monomineralic, single-crystal inclusion or it is associated with SiC (moissanite), CO 2 and CH 4 in polyphase inclusions . This rare record of diamond occurring with moissanite as fluid-inclusion daughter minerals implies the crystallization of diamond and moissanite from a supercritical fluid at reducing conditions. Thermodynamic modelling suggests that diamond-bearing gneisses attained P-T conditions of ≥3.5 GPa and 800-850 ºC, similar to eclogites and garnet peridotites. We argue that diamond formed when carbonaceous sediment underwent UHP metamorphism at mantle depth exceeding 100 km during continental subduction in the Late Cretaceous ( c . 95 to 92 Ma). The finding of diamond confirms UHP metamorphism in the Pohorje Mountains, the most deeply subducted part of Austroalpine units. This article is protected by copyright. All rights reserved.

Description: Anion exchanger 1 (AE1), also known as band 3 or SLC4A1, plays a key role in the removal of carbon dioxide from tissues by facilitating the exchange of chloride and bicarbonate across the plasma membrane of erythrocytes. An isoform of AE1 is also present in the kidney. Specific mutations in human AE1 cause several types of hereditary hemolytic anemias and/or distal renal tubular acidosis. Here we report the crystal structure of the band 3 anion exchanger domain (AE1(CTD)) at 3.5 angstroms. The structure is locked in an outward-facing open conformation by an inhibitor. Comparing this structure with a substrate-bound structure of the uracil transporter UraA in an inward-facing conformation allowed us to identify the anion-binding position in the AE1(CTD), and to propose a possible transport mechanism that could explain why selected mutations lead to disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arakawa, Takatoshi -- Kobayashi-Yurugi, Takami -- Alguel, Yilmaz -- Iwanari, Hiroko -- Hatae, Hinako -- Iwata, Momi -- Abe, Yoshito -- Hino, Tomoya -- Ikeda-Suno, Chiyo -- Kuma, Hiroyuki -- Kang, Dongchon -- Murata, Takeshi -- Hamakubo, Takao -- Cameron, Alexander D -- Kobayashi, Takuya -- Hamasaki, Naotaka -- Iwata, So -- BB/D019516/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G023425/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- WT089809/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Nov 6;350(6261):680-4. doi: 10.1126/science.aaa4335.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. ; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. ; Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire OX11 0FA, UK. ; Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan. ; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch-cho, Sasebo, Nagasaki 859-3298, Japan. ; Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. ; Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ; Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. ; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage, Chiba 263-8522, Japan. ; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire OX11 0FA, UK. School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. ; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Platform for Drug Discovery, Informatics, and Structural Life Science, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. ; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire OX11 0FA, UK. Platform for Drug Discovery, Informatics, and Structural Life Science, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26542571" target="_blank"〉PubMed〈/a〉

Description: We explore the effect of varying the mass of a seed black hole on the resulting black hole mass–bulge mass relation at z ~ 0, using a semi-analytic model of galaxy formation combined with large cosmological N -body simulations. We constrain our model by requiring that the observed properties of galaxies at z ~ 0 are reproduced. In keeping with previous semi-analytic models, we place a seed black hole immediately after a galaxy forms. When the mass of the seed is set at 10 5 M , we find that the model results become inconsistent with recent observational results of the black hole mass–bulge mass relation for dwarf galaxies. In particular, the model predicts that bulges with ~10 9 M harbour larger black holes than observed. On the other hand, when we employ seed black holes of 10 3 M or select their mass randomly within a 10 3–5 M range, the resulting relation is consistent with observation estimates, including the observed dispersion. We find that, to obtain stronger constraints on the mass of seed black holes, observations of less massive bulges at z ~ 0 are a more powerful comparison than the relations at higher redshifts.

Description: We report on electronic transport measurements through a silicon double quantum dot consisting of a donor and a quantum dot. Transport spectra show resonant tunneling peaks involving different valley states, which illustrate the valley splitting in a quantum dot on a Si/SiO 2 interface. The detailed gate bias dependence of double dot transport allows a first direct observation of the valley splitting in the quantum dot, which is controllable between 160 and 240  μ eV with an electric field dependence 1.2 ± 0.2 meV/(MV/m). A large valley splitting is an essential requirement for implementing a physical electron spin qubit in a silicon quantum dot.

Description: Abstract The Early Cretaceous Ontong Java Plateau (OJP) in the southwestern Pacific Ocean is the largest oceanic plateau by volume on Earth, and a broad range of observations has been conducted to reveal its formation and evolution. However, because seafloor seismic observations of the OJP and surrounding areas have been insufficient so far, such experiments are capable of generating additional information regarding the crustal and mantle structure of the OJP. To image seismic velocity discontinuities from the crust to the uppermost mantle, we applied receiver function (RF) analysis to seismic records acquired by 17 broadband ocean bottom seismometers deployed across the region in and around the OJP and 3 broadband stations located on ocean islands in Micronesia (one: permanent, two: temporary). The results revealed mid‐crustal discontinuities and the Moho at depths of 10–20 km and 30–40 km (from the top of the basement), respectively, in the central OJP. Moreover, a mantle discontinuity was also imaged at the depth of 55–60 km (from the top of the basement) in the central OJP. These boundaries were not imaged outside the OJP, implying they are characteristic features of the OJP. In addition, RF images showed Moho signals at the depth of 20 km in the eastern OJP, where few previous seismic exploration surveys have been conducted. This depth is comparable with that found in the Manihiki and Hikurangi plateaus that were potentially separated from the OJP.

Description: We present newly developed tapered capillaries with a scintillator window, which enable us to count single protons at the RIKEN cell irradiation setup. Their potential for performing single proton irradiation experiments at our beamline setup is demonstrated with CR39 samples, showing a single proton detection fidelity of 98%.

Description: This paper describes the development study of the beam emission spectroscopy (BES) for the turbulent transport study in Heliotron J. Modification of the sightlines (10 × 4 for edge and 10 × 2 for edge) enables us to obtain 2-dimensional BES imaging. The cooling effect on the reduction in the electrical noise of avalanche photodiode (APD) assembly has been investigated using a refrigerant cooling system. When the temperature of the APD element has set to be −20 °C, the electrical noise can be reduced more than 50%. The measurement error of the phase difference in the case of low signal level has been tested by two light-emitting diode lamps. The APD cooling has an effect to improve the measurement error at the low signal level of APD.