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  • 1
    Publication Date: 2018-11-06
    Description: Human mucosal tissues and skin contain two distinct types of dendritic cell (DC) subsets, epidermal Langerhans cells (LCs) and dermal DCs, which can be distinguished by the expression of C-type lectin receptors, Langerin and DC-SIGN, respectively. Although peripheral blood monocytes differentiate into these distinct subsets, monocyte-derived LCs (moLCs) induced by coculture with GM-CSF, IL-4, and TGF-β1 coexpress both Langerin and DC-SIGN, suggesting that the environmental cues remain unclear. In this study, we show that LC differentiation is TGF-β1 dependent and that cofactors such as IL-4 and TNF-α promote TGF-β1–dependent LC differentiation into Langerin + DC-SIGN – moLCs but continuous exposure to IL-4 blocks differentiation. Steroids such as dexamethasone greatly enhanced TNF-α–induced moLC differentiation and blocked DC-SIGN expression. Consistent with primary LCs, dexamethasone-treated moLCs express CD1a, whereas monocyte-derived DCs (moDCs) express CD1b, CD1c, and CD1d. moDCs but not moLCs produced inflammatory cytokines after stimulation with CD1b and CD1d ligands mycolic acid and α-galactosylceramide, respectively. Strikingly, CD1a triggering with squalene on moLCs but not moDCs induced strong IL-22-producing CD4 + helper T cell responses. As IL-22 is an important cytokine in the maintenance of skin homeostasis, these data suggest that CD1a on LCs is involved in maintaining the immune barrier in the skin.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2011-01-08
    Description: A young and energetic pulsar powers the well-known Crab Nebula. Here, we describe two separate gamma-ray (photon energy greater than 100 mega-electron volts) flares from this source detected by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. The first flare occurred in February 2009 and lasted approximately 16 days. The second flare was detected in September 2010 and lasted approximately 4 days. During these outbursts, the gamma-ray flux from the nebula increased by factors of four and six, respectively. The brevity of the flares implies that the gamma rays were emitted via synchrotron radiation from peta-electron-volt (10(15) electron volts) electrons in a region smaller than 1.4 x 10(-2) parsecs. These are the highest-energy particles that can be associated with a discrete astronomical source, and they pose challenges to particle acceleration theory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abdo, A A -- Ackermann, M -- Ajello, M -- Allafort, A -- Baldini, L -- Ballet, J -- Barbiellini, G -- Bastieri, D -- Bechtol, K -- Bellazzini, R -- Berenji, B -- Blandford, R D -- Bloom, E D -- Bonamente, E -- Borgland, A W -- Bouvier, A -- Brandt, T J -- Bregeon, J -- Brez, A -- Brigida, M -- Bruel, P -- Buehler, R -- Buson, S -- Caliandro, G A -- Cameron, R A -- Cannon, A -- Caraveo, P A -- Casandjian, J M -- Celik, O -- Charles, E -- Chekhtman, A -- Cheung, C C -- Chiang, J -- Ciprini, S -- Claus, R -- Cohen-Tanugi, J -- Costamante, L -- Cutini, S -- D'Ammando, F -- Dermer, C D -- de Angelis, A -- de Luca, A -- de Palma, F -- Digel, S W -- do Couto e Silva, E -- Drell, P S -- Drlica-Wagner, A -- Dubois, R -- Dumora, D -- Favuzzi, C -- Fegan, S J -- Ferrara, E C -- Focke, W B -- Fortin, P -- Frailis, M -- Fukazawa, Y -- Funk, S -- Fusco, P -- Gargano, F -- Gasparrini, D -- Gehrels, N -- Germani, S -- Giglietto, N -- Giordano, F -- Giroletti, M -- Glanzman, T -- Godfrey, G -- Grenier, I A -- Grondin, M-H -- Grove, J E -- Guiriec, S -- Hadasch, D -- Hanabata, Y -- Harding, A K -- Hayashi, K -- Hayashida, M -- Hays, E -- Horan, D -- Itoh, R -- Johannesson, G -- Johnson, A S -- Johnson, T J -- Khangulyan, D -- Kamae, T -- Katagiri, H -- Kataoka, J -- Kerr, M -- Knodlseder, J -- Kuss, M -- Lande, J -- Latronico, L -- Lee, S-H -- Lemoine-Goumard, M -- Longo, F -- Loparco, F -- Lubrano, P -- Madejski, G M -- Makeev, A -- Marelli, M -- Mazziotta, M N -- McEnery, J E -- Michelson, P F -- Mitthumsiri, W -- Mizuno, T -- Moiseev, A A -- Monte, C -- Monzani, M E -- Morselli, A -- Moskalenko, I V -- Murgia, S -- Nakamori, T -- Naumann-Godo, M -- Nolan, P L -- Norris, J P -- Nuss, E -- Ohsugi, T -- Okumura, A -- Omodei, N -- Ormes, J F -- Ozaki, M -- Paneque, D -- Parent, D -- Pelassa, V -- Pepe, M -- Pesce-Rollins, M -- Pierbattista, M -- Piron, F -- Porter, T A -- Raino, S -- Rando, R -- Ray, P S -- Razzano, M -- Reimer, A -- Reimer, O -- Reposeur, T -- Ritz, S -- Romani, R W -- Sadrozinski, H F-W -- Sanchez, D -- Saz Parkinson, P M -- Scargle, J D -- Schalk, T L -- Sgro, C -- Siskind, E J -- Smith, P D -- Spandre, G -- Spinelli, P -- Strickman, M S -- Suson, D J -- Takahashi, H -- Takahashi, T -- Tanaka, T -- Thayer, J B -- Thompson, D J -- Tibaldo, L -- Torres, D F -- Tosti, G -- Tramacere, A -- Troja, E -- Uchiyama, Y -- Vandenbroucke, J -- Vasileiou, V -- Vianello, G -- Vitale, V -- Wang, P -- Wood, K S -- Yang, Z -- Ziegler, M -- New York, N.Y. -- Science. 2011 Feb 11;331(6018):739-42. doi: 10.1126/science.1199705. Epub 2011 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Research Council Research Associate, National Academy of Sciences, Washington, DC 20001, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21212321" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-11-23
    Description: Gamma-ray burst (GRB) 130427A is one of the most energetic GRBs ever observed. The initial pulse up to 2.5 seconds is possibly the brightest well-isolated pulse observed to date. A fine time resolution spectral analysis shows power-law decays of the peak energy from the onset of the pulse, consistent with models of internal synchrotron shock pulses. However, a strongly correlated power-law behavior is observed between the luminosity and the spectral peak energy that is inconsistent with curvature effects arising in the relativistic outflow. It is difficult for any of the existing models to account for all of the observed spectral and temporal behaviors simultaneously.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Preece, R -- Burgess, J Michael -- von Kienlin, A -- Bhat, P N -- Briggs, M S -- Byrne, D -- Chaplin, V -- Cleveland, W -- Collazzi, A C -- Connaughton, V -- Diekmann, A -- Fitzpatrick, G -- Foley, S -- Gibby, M -- Giles, M -- Goldstein, A -- Greiner, J -- Gruber, D -- Jenke, P -- Kippen, R M -- Kouveliotou, C -- McBreen, S -- Meegan, C -- Paciesas, W S -- Pelassa, V -- Tierney, D -- van der Horst, A J -- Wilson-Hodge, C -- Xiong, S -- Younes, G -- Yu, H-F -- Ackermann, M -- Ajello, M -- Axelsson, M -- Baldini, L -- Barbiellini, G -- Baring, M G -- Bastieri, D -- Bellazzini, R -- Bissaldi, E -- Bonamente, E -- Bregeon, J -- Brigida, M -- Bruel, P -- Buehler, R -- Buson, S -- Caliandro, G A -- Cameron, R A -- Caraveo, P A -- Cecchi, C -- Charles, E -- Chekhtman, A -- Chiang, J -- Chiaro, G -- Ciprini, S -- Claus, R -- Cohen-Tanugi, J -- Cominsky, L R -- Conrad, J -- D'Ammando, F -- de Angelis, A -- de Palma, F -- Dermer, C D -- Desiante, R -- Digel, S W -- Di Venere, L -- Drell, P S -- Drlica-Wagner, A -- Favuzzi, C -- Franckowiak, A -- Fukazawa, Y -- Fusco, P -- Gargano, F -- Gehrels, N -- Germani, S -- Giglietto, N -- Giordano, F -- Giroletti, M -- Godfrey, G -- Granot, J -- Grenier, I A -- Guiriec, S -- Hadasch, D -- Hanabata, Y -- Harding, A K -- Hayashida, M -- Iyyani, S -- Jogler, T -- Johannesson, G -- Kawano, T -- Knodlseder, J -- Kocevski, D -- Kuss, M -- Lande, J -- Larsson, J -- Larsson, S -- Latronico, L -- Longo, F -- Loparco, F -- Lovellette, M N -- Lubrano, P -- Mayer, M -- Mazziotta, M N -- Michelson, P F -- Mizuno, T -- Monzani, M E -- Moretti, E -- Morselli, A -- Murgia, S -- Nemmen, R -- Nuss, E -- Nymark, T -- Ohno, M -- Ohsugi, T -- Okumura, A -- Omodei, N -- Orienti, M -- Paneque, D -- Perkins, J S -- Pesce-Rollins, M -- Piron, F -- Pivato, G -- Porter, T A -- Racusin, J L -- Raino, S -- Rando, R -- Razzano, M -- Razzaque, S -- Reimer, A -- Reimer, O -- Ritz, S -- Roth, M -- Ryde, F -- Sartori, A -- Scargle, J D -- Schulz, A -- Sgro, C -- Siskind, E J -- Spandre, G -- Spinelli, P -- Suson, D J -- Tajima, H -- Takahashi, H -- Thayer, J G -- Thayer, J B -- Tibaldo, L -- Tinivella, M -- Torres, D F -- Tosti, G -- Troja, E -- Usher, T L -- Vandenbroucke, J -- Vasileiou, V -- Vianello, G -- Vitale, V -- Werner, M -- Winer, B L -- Wood, K S -- Zhu, S -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):51-4. doi: 10.1126/science.1242302. Epub 2013 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Space Science, University of Alabama in Huntsville, Huntsville, AL 35899, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24263132" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-11-23
    Description: The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest gamma-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ackermann, M -- Ajello, M -- Asano, K -- Atwood, W B -- Axelsson, M -- Baldini, L -- Ballet, J -- Barbiellini, G -- Baring, M G -- Bastieri, D -- Bechtol, K -- Bellazzini, R -- Bissaldi, E -- Bonamente, E -- Bregeon, J -- Brigida, M -- Bruel, P -- Buehler, R -- Burgess, J Michael -- Buson, S -- Caliandro, G A -- Cameron, R A -- Caraveo, P A -- Cecchi, C -- Chaplin, V -- Charles, E -- Chekhtman, A -- Cheung, C C -- Chiang, J -- Chiaro, G -- Ciprini, S -- Claus, R -- Cleveland, W -- Cohen-Tanugi, J -- Collazzi, A -- Cominsky, L R -- Connaughton, V -- Conrad, J -- Cutini, S -- D'Ammando, F -- de Angelis, A -- DeKlotz, M -- de Palma, F -- Dermer, C D -- Desiante, R -- Diekmann, A -- Di Venere, L -- Drell, P S -- Drlica-Wagner, A -- Favuzzi, C -- Fegan, S J -- Ferrara, E C -- Finke, J -- Fitzpatrick, G -- Focke, W B -- Franckowiak, A -- Fukazawa, Y -- Funk, S -- Fusco, P -- Gargano, F -- Gehrels, N -- Germani, S -- Gibby, M -- Giglietto, N -- Giles, M -- Giordano, F -- Giroletti, M -- Godfrey, G -- Granot, J -- Grenier, I A -- Grove, J E -- Gruber, D -- Guiriec, S -- Hadasch, D -- Hanabata, Y -- Harding, A K -- Hayashida, M -- Hays, E -- Horan, D -- Hughes, R E -- Inoue, Y -- Jogler, T -- Johannesson, G -- Johnson, W N -- Kawano, T -- Knodlseder, J -- Kocevski, D -- Kuss, M -- Lande, J -- Larsson, S -- Latronico, L -- Longo, F -- Loparco, F -- Lovellette, M N -- Lubrano, P -- Mayer, M -- Mazziotta, M N -- McEnery, J E -- Michelson, P F -- Mizuno, T -- Moiseev, A A -- Monzani, M E -- Moretti, E -- Morselli, A -- Moskalenko, I V -- Murgia, S -- Nemmen, R -- Nuss, E -- Ohno, M -- Ohsugi, T -- Okumura, A -- Omodei, N -- Orienti, M -- Paneque, D -- Pelassa, V -- Perkins, J S -- Pesce-Rollins, M -- Petrosian, V -- Piron, F -- Pivato, G -- Porter, T A -- Racusin, J L -- Raino, S -- Rando, R -- Razzano, M -- Razzaque, S -- Reimer, A -- Reimer, O -- Ritz, S -- Roth, M -- Ryde, F -- Sartori, A -- Parkinson, P M Saz -- Scargle, J D -- Schulz, A -- Sgro, C -- Siskind, E J -- Sonbas, E -- Spandre, G -- Spinelli, P -- Tajima, H -- Takahashi, H -- Thayer, J G -- Thayer, J B -- Thompson, D J -- Tibaldo, L -- Tinivella, M -- Torres, D F -- Tosti, G -- Troja, E -- Usher, T L -- Vandenbroucke, J -- Vasileiou, V -- Vianello, G -- Vitale, V -- Winer, B L -- Wood, K S -- Yamazaki, R -- Younes, G -- Yu, H-F -- Zhu, S J -- Bhat, P N -- Briggs, M S -- Byrne, D -- Foley, S -- Goldstein, A -- Jenke, P -- Kippen, R M -- Kouveliotou, C -- McBreen, S -- Meegan, C -- Paciesas, W S -- Preece, R -- Rau, A -- Tierney, D -- van der Horst, A J -- von Kienlin, A -- Wilson-Hodge, C -- Xiong, S -- Cusumano, G -- La Parola, V -- Cummings, J R -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):42-7. doi: 10.1126/science.1242353. Epub 2013 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Deutsches Elektronen Synchrotron DESY, D-15738 Zeuthen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24263133" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-06-04
    Description: Through their functional diversification, distinct lineages of CD4(+) T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma, Crohn's disease, coeliac disease, vitiligo, multiple sclerosis and type 1 diabetes. Although these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for BACH2 in the maintenance of immune homeostasis has not been established. Here, by studying mice in which the Bach2 gene is disrupted, we define BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4(+) T cells. BACH2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg-cell-dependent. Assessment of the genome-wide function of BACH2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, BACH2 constrained full effector differentiation within TH1, TH2 and TH17 cell lineages. These findings identify BACH2 as a key regulator of CD4(+) T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710737/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710737/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roychoudhuri, Rahul -- Hirahara, Kiyoshi -- Mousavi, Kambiz -- Clever, David -- Klebanoff, Christopher A -- Bonelli, Michael -- Sciume, Giuseppe -- Zare, Hossein -- Vahedi, Golnaz -- Dema, Barbara -- Yu, Zhiya -- Liu, Hui -- Takahashi, Hayato -- Rao, Mahadev -- Muranski, Pawel -- Crompton, Joseph G -- Punkosdy, George -- Bedognetti, Davide -- Wang, Ena -- Hoffmann, Victoria -- Rivera, Juan -- Marincola, Francesco M -- Nakamura, Atsushi -- Sartorelli, Vittorio -- Kanno, Yuka -- Gattinoni, Luca -- Muto, Akihiko -- Igarashi, Kazuhiko -- O'Shea, John J -- Restifo, Nicholas P -- Z01 BC011037-01/Intramural NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- ZIA BC011037-02/Intramural NIH HHS/ -- England -- Nature. 2013 Jun 27;498(7455):506-10. doi: 10.1038/nature12199. Epub 2013 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. roychoudhuri@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23728300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoimmunity/immunology ; Basic-Leucine Zipper Transcription Factors/deficiency/genetics/*metabolism ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Differentiation/genetics/immunology ; Female ; Forkhead Transcription Factors/genetics/metabolism ; Homeostasis/genetics/*immunology ; Humans ; Immune Tolerance/genetics/immunology ; Inflammation/genetics/immunology/mortality/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes, Regulatory/cytology/drug effects/*immunology/metabolism ; Transforming Growth Factor beta/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-01-08
    Description: How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours. In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source containing a black hole of nine solar masses (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought. This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion--not the actual rate--would then be the critical factor causing large-amplitude oscillations in long-period systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kimura, Mariko -- Isogai, Keisuke -- Kato, Taichi -- Ueda, Yoshihiro -- Nakahira, Satoshi -- Shidatsu, Megumi -- Enoto, Teruaki -- Hori, Takafumi -- Nogami, Daisaku -- Littlefield, Colin -- Ishioka, Ryoko -- Chen, Ying-Tung -- King, Sun-Kun -- Wen, Chih-Yi -- Wang, Shiang-Yu -- Lehner, Matthew J -- Schwamb, Megan E -- Wang, Jen-Hung -- Zhang, Zhi-Wei -- Alcock, Charles -- Axelrod, Tim -- Bianco, Federica B -- Byun, Yong-Ik -- Chen, Wen-Ping -- Cook, Kem H -- Kim, Dae-Won -- Lee, Typhoon -- Marshall, Stuart L -- Pavlenko, Elena P -- Antonyuk, Oksana I -- Antonyuk, Kirill A -- Pit, Nikolai V -- Sosnovskij, Aleksei A -- Babina, Julia V -- Baklanov, Aleksei V -- Pozanenko, Alexei S -- Mazaeva, Elena D -- Schmalz, Sergei E -- Reva, Inna V -- Belan, Sergei P -- Inasaridze, Raguli Ya -- Tungalag, Namkhai -- Volnova, Alina A -- Molotov, Igor E -- de Miguel, Enrique -- Kasai, Kiyoshi -- Stein, William L -- Dubovsky, Pavol A -- Kiyota, Seiichiro -- Miller, Ian -- Richmond, Michael -- Goff, William -- Andreev, Maksim V -- Takahashi, Hiromitsu -- Kojiguchi, Naoto -- Sugiura, Yuki -- Takeda, Nao -- Yamada, Eiji -- Matsumoto, Katsura -- James, Nick -- Pickard, Roger D -- Tordai, Tamas -- Maeda, Yutaka -- Ruiz, Javier -- Miyashita, Atsushi -- Cook, Lewis M -- Imada, Akira -- Uemura, Makoto -- England -- Nature. 2016 Jan 7;529(7584):54-8. doi: 10.1038/nature16452.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Astronomy, Graduate School of Science, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan. ; JEM Mission Operations and Integration Center, Human Spaceflight Technology Directorate, Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505, Japan. ; MAXI team, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; The Hakubi Center for Advanced Research, Kyoto University, Kyoto 606-8302, Japan. ; Astronomy Department, Wesleyan University, Middletown, Connecticut 06459, USA. ; Institute of Astronomy and Astrophysics, Academia Sinica, 11F of Astronomy-Mathematics Building, AS/NTU No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan. ; Department of Physics and Astronomy, University of Pennsylvania, 209 South 33rd Street, Philadelphia, Pennsylvania 19125, USA. ; Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, Massachusetts 02138, USA. ; Steward Observatory, University of Arizona, Tucson, Arizona 85721, USA. ; Center for Cosmology and Particle Physics, New York University, 4 Washington Place, New York, New York 10003, USA. ; Department of Astronomy and University Observatory, Yonsei University, Seoul 120-749, South Korea. ; Institute of Astronomy and Department of Physics, National Central University, Chung-Li 32054, Taiwan. ; Max Planck Institute for Astronomy, Konigstuhl 17, 69117 Heidelberg, Germany. ; Kavli Institute for Particle Astrophysics and Cosmology (KIPAC), Stanford University, 452 Lomita Mall, Stanford, California 94309, USA. ; Crimean Astrophysical Observatory, 298409 Nauchny, Crimea. ; Space Research Institute, Russian Academy of Sciences, 117997 Moscow, Russia. ; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia. ; Leibniz Institute for Astrophysics, Potsdam, Germany. ; Fesenkov Astrophysical Institute, Almaty, Kazakhstan. ; Kharadze Abastumani Astrophysical Observatory, Ilia State University, Tbilisi, Georgia. ; Institute of Astronomy and Geophysics, Mongolian Academy of Sciences, Ulaanbaatar 13343, Mongolia. ; Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, Moscow, Russia. ; Departamento de Fisica Aplicada, Facultad de Ciencias Experimentales, Universidad de Huelva, 21071 Huelva, Spain. ; Center for Backyard Astrophysics, Observatorio del CIECEM, Parque Dunar, Matalascanas, 21760 Almonte, Huelva, Spain. ; Baselstrasse 133D, CH-4132 Muttenz, Switzerland. ; 6025 Calle Paraiso, Las Cruces, New Mexico 88012, USA. ; Vihorlat Observatory, Mierova 4, Humenne, Slovakia. ; Variable Star Observers League in Japan (VSOLJ), 7-1 Kitahatsutomi, Kamagaya, Chiba 273-0126, Japan. ; Furzehill House, Ilston, Swansea SA2 7LE, UK. ; Physics Department, Rochester Institute of Technology, Rochester, New York 14623, USA. ; American Association of Variable Star Observers (AAVSO), 13508 Monitor Lane, Sutter Creek, California 95685, USA. ; Institute of Astronomy, Russian Academy of Sciences, 361605 Peak Terskol, Kabardino-Balkaria, Russia. ; International Center for Astronomical, Medical and Ecological Research of National Academy of Sciences of Ukraine (NASU), 27 Akademika Zabolotnoho street, 03680 Kiev, Ukraine. ; Department of Physical Science, School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan. ; Osaka Kyoiku University, 4-698-1 Asahigaoka, Kashiwara, Osaka 582-8582, Japan. ; 1 Tavistock Road, Chelmsford, Essex CM1 6JL, UK. ; The British Astronomical Association, Variable Star Section (BAA VSS), Burlington House, Piccadilly, London W1J 0DU, UK. ; 3 The Birches, Shobdon, Leominster, Herefordshire HR6 9NG, UK. ; Polaris Observatory, Hungarian Astronomical Association, Laborc utca 2/c, 1037 Budapest, Hungary. ; 112-14 Kaminishiyama-machi, Nagasaki, Nagasaki 850-0006, Japan. ; Observatorio de Cantabria, Carretera de Rocamundo sin numero, Valderredible, Cantabria, Spain. ; Instituto de Fisica de Cantabria (CSIC-UC), Avenida Los Castros sin numero, E-39005 Santander, Cantabria, Spain. ; Agrupacion Astronomica Cantabra, Apartado 573, 39080 Santander, Spain. ; Seikei Meteorological Observatory, Seikei High School, Kichijoji-kitamachi 3-10-13, Musashino, Tokyo 180-8633, Japan. ; Center for Backyard Astrophysics (Concord), 1730 Helix Court, Concord, California 94518, USA. ; Kwasan and Hida Observatories, Kyoto University, Kitakazan-Ohmine-cho, Yamashina-ku, Kyoto 607-8471, Japan. ; Hiroshima Astrophysical Science Center, Hiroshima University, Kagamiyama 1-3-1, Higashi-Hiroshima, Hiroshima 739-8526, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26738590" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-11-03
    Description: The light emitted by stars and accreting compact objects through the history of the universe is encoded in the intensity of the extragalactic background light (EBL). Knowledge of the EBL is important to understand the nature of star formation and galaxy evolution, but direct measurements of the EBL are limited by galactic and other foreground emissions. Here, we report an absorption feature seen in the combined spectra of a sample of gamma-ray blazars out to a redshift of z approximately 1.6. This feature is caused by attenuation of gamma rays by the EBL at optical to ultraviolet frequencies and allowed us to measure the EBL flux density in this frequency band.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ackermann, M -- Ajello, M -- Allafort, A -- Schady, P -- Baldini, L -- Ballet, J -- Barbiellini, G -- Bastieri, D -- Bellazzini, R -- Blandford, R D -- Bloom, E D -- Borgland, A W -- Bottacini, E -- Bouvier, A -- Bregeon, J -- Brigida, M -- Bruel, P -- Buehler, R -- Buson, S -- Caliandro, G A -- Cameron, R A -- Caraveo, P A -- Cavazzuti, E -- Cecchi, C -- Charles, E -- Chaves, R C G -- Chekhtman, A -- Cheung, C C -- Chiang, J -- Chiaro, G -- Ciprini, S -- Claus, R -- Cohen-Tanugi, J -- Conrad, J -- Cutini, S -- D'Ammando, F -- de Palma, F -- Dermer, C D -- Digel, S W -- do Couto e Silva, E -- Dominguez, A -- Drell, P S -- Drlica-Wagner, A -- Favuzzi, C -- Fegan, S J -- Focke, W B -- Franckowiak, A -- Fukazawa, Y -- Funk, S -- Fusco, P -- Gargano, F -- Gasparrini, D -- Gehrels, N -- Germani, S -- Giglietto, N -- Giordano, F -- Giroletti, M -- Glanzman, T -- Godfrey, G -- Grenier, I A -- Grove, J E -- Guiriec, S -- Gustafsson, M -- Hadasch, D -- Hayashida, M -- Hays, E -- Jackson, M S -- Jogler, T -- Kataoka, J -- Knodlseder, J -- Kuss, M -- Lande, J -- Larsson, S -- Latronico, L -- Longo, F -- Loparco, F -- Lovellette, M N -- Lubrano, P -- Mazziotta, M N -- McEnery, J E -- Mehault, J -- Michelson, P F -- Mizuno, T -- Monte, C -- Monzani, M E -- Morselli, A -- Moskalenko, I V -- Murgia, S -- Tramacere, A -- Nuss, E -- Greiner, J -- Ohno, M -- Ohsugi, T -- Omodei, N -- Orienti, M -- Orlando, E -- Ormes, J F -- Paneque, D -- Perkins, J S -- Pesce-Rollins, M -- Piron, F -- Pivato, G -- Porter, T A -- Raino, S -- Rando, R -- Razzano, M -- Razzaque, S -- Reimer, A -- Reimer, O -- Reyes, L C -- Ritz, S -- Rau, A -- Romoli, C -- Roth, M -- Sanchez-Conde, M -- Sanchez, D A -- Scargle, J D -- Sgro, C -- Siskind, E J -- Spandre, G -- Spinelli, P -- Stawarz, Lukasz -- Suson, D J -- Takahashi, H -- Tanaka, T -- Thayer, J G -- Thompson, D J -- Tibaldo, L -- Tinivella, M -- Torres, D F -- Tosti, G -- Troja, E -- Usher, T L -- Vandenbroucke, J -- Vasileiou, V -- Vianello, G -- Vitale, V -- Waite, A P -- Winer, B L -- Wood, K S -- Wood, M -- New York, N.Y. -- Science. 2012 Nov 30;338(6111):1190-2. doi: 10.1126/science.1227160. Epub 2012 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Deutsches Elektronen Synchrotron DESY, D-15738 Zeuthen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23118013" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2018-12-01
    Description: Background/Aim: While the PD-L1 22C3 pharmDx assay is an FDA-approved diagnostic assay for pembrolizumab use, not every pathology laboratory has the Dako Autostainer to use this assay. Since Ventana BenchMark platforms are more common, the Ventana SP263 assay can be used to inform treatment decisions involving nivolumab and pembrolizumab in non-small cell lung cancer (NSCLC). However, some studies have shown discordant results between the two assays. This study aimed was to compare PD-L1 expression using these two assays. Materials and Methods: A total of 100 samples from consecutive cases of resected NSCLC were tested using the two PD-L1 assays. Results: The agreement rates of the two assays were 88-97% at various cut-offs. There was no significant difference between 22C3 and SP263 in tumour proportion score (p=0.455). Conclusion: The SP263 assay can be used in the place of the 22C3 assay for PD-L1 testing, for guiding therapy with PD-1 axis inhibitors in NSCLC.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 9
    Publication Date: 2018-12-02
    Description: Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l -serine biosynthesis: PHGDH , PSAT1 , and PSPH . l -Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient’s skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient’s stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.
    Print ISSN: 0022-2275
    Electronic ISSN: 1539-7262
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 10
    Publication Date: 2012-09-08
    Description: Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Djebali, Sarah -- Davis, Carrie A -- Merkel, Angelika -- Dobin, Alex -- Lassmann, Timo -- Mortazavi, Ali -- Tanzer, Andrea -- Lagarde, Julien -- Lin, Wei -- Schlesinger, Felix -- Xue, Chenghai -- Marinov, Georgi K -- Khatun, Jainab -- Williams, Brian A -- Zaleski, Chris -- Rozowsky, Joel -- Roder, Maik -- Kokocinski, Felix -- Abdelhamid, Rehab F -- Alioto, Tyler -- Antoshechkin, Igor -- Baer, Michael T -- Bar, Nadav S -- Batut, Philippe -- Bell, Kimberly -- Bell, Ian -- Chakrabortty, Sudipto -- Chen, Xian -- Chrast, Jacqueline -- Curado, Joao -- Derrien, Thomas -- Drenkow, Jorg -- Dumais, Erica -- Dumais, Jacqueline -- Duttagupta, Radha -- Falconnet, Emilie -- Fastuca, Meagan -- Fejes-Toth, Kata -- Ferreira, Pedro -- Foissac, Sylvain -- Fullwood, Melissa J -- Gao, Hui -- Gonzalez, David -- Gordon, Assaf -- Gunawardena, Harsha -- Howald, Cedric -- Jha, Sonali -- Johnson, Rory -- Kapranov, Philipp -- King, Brandon -- Kingswood, Colin -- Luo, Oscar J -- Park, Eddie -- Persaud, Kimberly -- Preall, Jonathan B -- Ribeca, Paolo -- Risk, Brian -- Robyr, Daniel -- Sammeth, Michael -- Schaffer, Lorian -- See, Lei-Hoon -- Shahab, Atif -- Skancke, Jorgen -- Suzuki, Ana Maria -- Takahashi, Hazuki -- Tilgner, Hagen -- Trout, Diane -- Walters, Nathalie -- Wang, Huaien -- Wrobel, John -- Yu, Yanbao -- Ruan, Xiaoan -- Hayashizaki, Yoshihide -- Harrow, Jennifer -- Gerstein, Mark -- Hubbard, Tim -- Reymond, Alexandre -- Antonarakis, Stylianos E -- Hannon, Gregory -- Giddings, Morgan C -- Ruan, Yijun -- Wold, Barbara -- Carninci, Piero -- Guigo, Roderic -- Gingeras, Thomas R -- 062023/Wellcome Trust/United Kingdom -- 1RC2HG005591/HG/NHGRI NIH HHS/ -- 249968/European Research Council/International -- P30 CA045508/CA/NCI NIH HHS/ -- R01 HG003700/HG/NHGRI NIH HHS/ -- R01HG003700/HG/NHGRI NIH HHS/ -- R37 GM062534/GM/NIGMS NIH HHS/ -- RC2 HG005591/HG/NHGRI NIH HHS/ -- U01 HG003147/HG/NHGRI NIH HHS/ -- U54 HG004555/HG/NHGRI NIH HHS/ -- U54 HG004557/HG/NHGRI NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- U54 HG004576/HG/NHGRI NIH HHS/ -- U54 HG007004/HG/NHGRI NIH HHS/ -- U54HG004555/HG/NHGRI NIH HHS/ -- U54HG004557/HG/NHGRI NIH HHS/ -- U54HG004558/HG/NHGRI NIH HHS/ -- U54HG004576/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Sep 6;489(7414):101-8. doi: 10.1038/nature11233.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation and UPF, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955620" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line ; DNA/*genetics ; DNA, Intergenic/genetics ; *Encyclopedias as Topic ; Enhancer Elements, Genetic ; Exons/genetics ; Gene Expression Profiling ; Genes/genetics ; Genome, Human/*genetics ; Genomics ; Humans ; *Molecular Sequence Annotation ; Polyadenylation/genetics ; Protein Isoforms/genetics ; RNA/biosynthesis/genetics ; RNA Editing/genetics ; RNA Splicing/genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Sequence Analysis, RNA ; Transcription, Genetic/*genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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