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  • 1
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    CYCLoPs: A Comprehensive Database Constructed from Automated Analysis of Protein Abundance and Subcellular Localization Patterns in Saccharomyces cerevisiae (2015)
    Genetics Society of America (GSA)
    Details
    Publication Date: 2015-06-12
    Description: Changes in protein subcellular localization and abundance are central to biological regulation in eukaryotic cells. Quantitative measures of protein dynamics in vivo are therefore highly useful for elucidating specific regulatory pathways. Using a combinatorial approach of yeast synthetic genetic array technology, high-content screening, and machine learning classifiers, we developed an automated platform to characterize protein localization and abundance patterns from images of log phase cells from the open-reading frame–green fluorescent protein collection in the budding yeast, Saccharomyces cerevisiae . For each protein, we produced quantitative profiles of localization scores for 16 subcellular compartments at single-cell resolution to trace proteome-wide relocalization in conditions over time. We generated a collection of ~300,000 micrographs, comprising more than 20 million cells and ~9 billion quantitative measurements. The images depict the localization and abundance dynamics of more than 4000 proteins under two chemical treatments and in a selected mutant background. Here, we describe CYCLoPs ( C ollection of Y east C ells Lo calization P attern s ), a web database resource that provides a central platform for housing and analyzing our yeast proteome dynamics datasets at the single cell level. CYCLoPs version 1.0 is available at http://cyclops.ccbr.utoronto.ca . CYCLoPs will provide a valuable resource for the yeast and eukaryotic cell biology communities and will be updated as new experiments become available.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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  • 2
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    The fossil wind structures of Eta Carinae: changes across one 5.54-yr cycle (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-31
    Description: Eta Carinae, the closest, active, massive binary containing a highly unstable Luminous Blue Variable, exhibits expanding, compressed wind shells, seen in emission, that are spatially and spectrally resolved by Hubble Space Telescope / Space Telescope Imaging Spectrograph . Starting in 2009 June, these structures were mapped across its 5.54-yr, highly elliptical, binary orbit to follow temporal changes in the light of [Fe iii ] 4659 Å and [Fe ii ] 4815 Å. The emissions trace portions of fossil wind shells, that were formed by wind–wind interactions across each cycle. Over the high-ionization state, dense arcs, photoionized by far-ultraviolet radiation from the hot secondary, are seen in [Fe iii ]. Other arcs, ionized by mid-ultraviolet radiation from the primary star, are seen in [Fe ii ]. The [Fe iii ] structures tend to be interior to [Fe ii ] structures that trace extensive, less disturbed primary wind. During the brief periastron passage when the secondary plunges deep into the primary's extremely dense wind, on the far side of primary star, high-ionization [Fe iii ] structures fade and reappear in [Fe ii ]. Multiple fossil wind structures were traced across the 5.7-yr monitoring interval. The strong similarity of the expanding [Fe ii ] shells suggests that the wind and photoionization properties of the massive binary have not changed substantially from one orbit to the next over the past several orbital cycles. These observations trace structures that can be used to test 3D hydrodynamical and radiative-transfer models of massive, interacting winds. They also provide a baseline for following future changes in Car, especially of its winds and photoionization properties.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    A strategy for modulation of enzymes in the ubiquitin system (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-01-05
    Description: The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815447/" 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/PMC3815447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Andreas -- Avvakumov, George -- Tong, Jiefei -- Fan, Yihui -- Zhao, Yanling -- Alberts, Philipp -- Persaud, Avinash -- Walker, John R -- Neculai, Ana-Mirela -- Neculai, Dante -- Vorobyov, Andrew -- Garg, Pankaj -- Beatty, Linda -- Chan, Pak-Kei -- Juang, Yu-Chi -- Landry, Marie-Claude -- Yeh, Christina -- Zeqiraj, Elton -- Karamboulas, Konstantina -- Allali-Hassani, Abdellah -- Vedadi, Masoud -- Tyers, Mike -- Moffat, Jason -- Sicheri, Frank -- Pelletier, Laurence -- Durocher, Daniel -- Raught, Brian -- Rotin, Daniela -- Yang, Jianhua -- Moran, Michael F -- Dhe-Paganon, Sirano -- Sidhu, Sachdev S -- 092076/Wellcome Trust/United Kingdom -- 092381/Wellcome Trust/United Kingdom -- 1R01NS072420-01/Canadian Institutes of Health Research/Canada -- MOP-102536/Canadian Institutes of Health Research/Canada -- MOP-111149/Canadian Institutes of Health Research/Canada -- MOP-13494/Canadian Institutes of Health Research/Canada -- MOP-57795/Canadian Institutes of Health Research/Canada -- R01 NS072420/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):590-5. doi: 10.1126/science.1230161. Epub 2013 Jan 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23287719" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Combinatorial Chemistry Techniques ; Conserved Sequence ; Drug Design ; Endopeptidases/chemistry/*metabolism ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Protease Inhibitors/chemistry/*isolation & purification/pharmacology ; Protein Conformation ; Protein Structure, Secondary ; Small Molecule Libraries ; Ubiquitin/chemistry/genetics/*metabolism ; Ubiquitin Thiolesterase/chemistry/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination/*drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-07-06
    Description: Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme-the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors-most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724525/" 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/PMC3724525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Timothy R -- Fridlyand, Jane -- Yan, Yibing -- Penuel, Elicia -- Burton, Luciana -- Chan, Emily -- Peng, Jing -- Lin, Eva -- Wang, Yulei -- Sosman, Jeff -- Ribas, Antoni -- Li, Jiang -- Moffat, John -- Sutherlin, Daniel P -- Koeppen, Hartmut -- Merchant, Mark -- Neve, Richard -- Settleman, Jeff -- K24 CA097588/CA/NCI NIH HHS/ -- England -- Nature. 2012 Jul 26;487(7408):505-9. doi: 10.1038/nature11249.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763448" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/*pharmacology ; Breast Neoplasms/*drug therapy/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; *Drug Resistance, Neoplasm/drug effects ; Female ; Hepatocyte Growth Factor/*metabolism/pharmacology ; Humans ; Indoles/*pharmacology ; Ligands ; Melanoma/*drug therapy/enzymology/genetics/pathology ; Mitogen-Activated Protein Kinases/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics ; Quinazolines/pharmacology ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, ErbB-2/genetics/metabolism ; Signal Transduction/drug effects ; Sulfonamides/*pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    MBNL proteins repress ES-cell-specific alternative splicing and reprogramming (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-06-07
    Description: Previous investigations of the core gene regulatory circuitry that controls the pluripotency of embryonic stem (ES) cells have largely focused on the roles of transcription, chromatin and non-coding RNA regulators. Alternative splicing represents a widely acting mode of gene regulation, yet its role in regulating ES-cell pluripotency and differentiation is poorly understood. Here we identify the muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of cassette exon alternative splicing events that are differentially regulated between ES cells and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ES-cell-like alternative splicing pattern for approximately half of these events, whereas overexpression of MBNL proteins in ES cells promotes differentiated-cell-like alternative splicing patterns. Among the MBNL-regulated events is an ES-cell-specific alternative splicing switch in the forkhead family transcription factor FOXP1 that controls pluripotency. Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells during somatic cell reprogramming.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933998/" 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/PMC3933998/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Hong -- Irimia, Manuel -- Ross, P Joel -- Sung, Hoon-Ki -- Alipanahi, Babak -- David, Laurent -- Golipour, Azadeh -- Gabut, Mathieu -- Michael, Iacovos P -- Nachman, Emil N -- Wang, Eric -- Trcka, Dan -- Thompson, Tadeo -- O'Hanlon, Dave -- Slobodeniuc, Valentina -- Barbosa-Morais, Nuno L -- Burge, Christopher B -- Moffat, Jason -- Frey, Brendan J -- Nagy, Andras -- Ellis, James -- Wrana, Jeffrey L -- Blencowe, Benjamin J -- R01 HG002439/HG/NHGRI NIH HHS/ -- R33 MH087908/MH/NIMH NIH HHS/ -- R33MH087908/MH/NIMH NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2013 Jun 13;498(7453):241-5. doi: 10.1038/nature12270. Epub 2013 Jun 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23739326" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing/genetics ; Amino Acid Motifs ; Animals ; Cell Differentiation/genetics ; Cell Line ; *Cellular Reprogramming ; DNA-Binding Proteins/chemistry/deficiency/genetics/*metabolism ; Embryonic Stem Cells/*cytology/*metabolism ; Fibroblasts/cytology/metabolism ; Forkhead Transcription Factors/metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; HeLa Cells ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Kinetics ; Mice ; RNA-Binding Proteins/chemistry/genetics/*metabolism ; Repressor Proteins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    INNATE IMMUNITY. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-06-13
    Description: Host recognition of pathogen-associated molecular patterns (PAMPs) initiates an innate immune response that is critical for pathogen elimination and engagement of adaptive immunity. Here we show that mammalian cells can detect and respond to the bacterial-derived monosaccharide heptose-1,7-bisphosphate (HBP). A metabolic intermediate in lipopolysaccharide biosynthesis, HBP is highly conserved in Gram-negative bacteria, yet absent from eukaryotic cells. Detection of HBP within the host cytosol activated the nuclear facto kappaB pathway in vitro and induced innate and adaptive immune responses in vivo. Moreover, we used a genome-wide RNA interference screen to uncover an innate immune signaling axis, mediated by phosphorylation-dependent oligomerization of the TRAF-interacting protein with forkhead-associated domain (TIFA) that is triggered by HBP. Thus, HBP is a PAMP that activates TIFA-dependent immunity to Gram-negative bacteria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gaudet, Ryan G -- Sintsova, Anna -- Buckwalter, Carolyn M -- Leung, Nelly -- Cochrane, Alan -- Li, Jianjun -- Cox, Andrew D -- Moffat, Jason -- Gray-Owen, Scott D -- HOP-13769/Canadian Institutes of Health Research/Canada -- MOP-15499/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1251-5. doi: 10.1126/science.aaa4921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. ; Vaccine Program, National Research Council, Ottawa, ON, Canada K1A 0R6. ; Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada M5S 3E1. ; Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8. scott.gray.owen@utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068852" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*immunology/metabolism ; Burkholderia/immunology ; Cytosol/chemistry/immunology ; Escherichia coli/immunology ; Flagellin/immunology ; Genetic Testing ; Gram-Negative Bacteria/*immunology/metabolism ; HEK293 Cells ; Host-Pathogen Interactions/genetics/*immunology ; Humans ; *Immunity, Innate ; Jurkat Cells ; NF-kappa B/immunology ; Neisseria gonorrhoeae/immunology ; Neisseria meningitidis/immunology ; RNA Interference ; Sugar Phosphates/analysis/*immunology/metabolism ; TNF Receptor-Associated Factor 6/immunology/metabolism
    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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  • 7
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    SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-12-25
    Description: The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. Here we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy. SMN interacts with senataxin, which is sometimes mutated in ataxia oculomotor apraxia type 2 and amyotrophic lateral sclerosis. Because POLR2A R1810me2s and SMN, like senataxin, are required for resolving RNA-DNA hybrids created by RNA polymerase II that form R-loops in transcription termination regions, we propose that R1810me2s, SMN, and senataxin are components of an R-loop resolution pathway. Defects in this pathway can influence transcription termination and may contribute to neurodegenerative disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Dorothy Yanling -- Gish, Gerald -- Braunschweig, Ulrich -- Li, Yue -- Ni, Zuyao -- Schmitges, Frank W -- Zhong, Guoqing -- Liu, Ke -- Li, Weiguo -- Moffat, Jason -- Vedadi, Masoud -- Min, Jinrong -- Pawson, Tony J -- Blencowe, Benjamin J -- Greenblatt, Jack F -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Jan 7;529(7584):48-53. doi: 10.1038/nature16469. Epub 2015 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4, Canada. ; Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26700805" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/*metabolism ; Cell Line ; DNA Damage ; Humans ; Methylation ; Neurodegenerative Diseases/genetics ; Protein Binding ; Protein Structure, Tertiary ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; RNA Helicases/genetics/metabolism ; RNA Polymerase II/*chemistry/*metabolism ; Survival of Motor Neuron 1 Protein/genetics/*metabolism ; Transcription Elongation, Genetic ; *Transcription Termination, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Sonar tracking of horizontally moving targets by the big brown bat Eptesicus fuscus (1985)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1985-06-14
    Description: When following a moving target, echolocating bats (Eptesicus fuscus) keep their heads aimed at the target's position. This tracking behavior seems not to involve predicting the target's trajectory, but is achieved by the bat's pointing its head at the target's last known position. The bat obtains frequent position updates by emitting sonar signals at a high rate. After the lag between head and target positions and the nonunity tracking gain were corrected for, bats' tracking accuracy in the horizontal plane was +/- 1.6 degree.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masters, W M -- Moffat, A J -- Simmons, J A -- New York, N.Y. -- Science. 1985 Jun 14;228(4705):1331-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/4001947" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chiroptera/*physiology ; Echolocation/*physiology ; Head ; Orientation/*physiology ; Predatory Behavior/physiology
    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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  • 9
    Electronic Resource
    Electronic Resource
    A Comparison of Methods for the Analysis of Adsorption-Desorption Isotherms of Microporous Solids (1995)
    s.l. : American Chemical Society
    Langmuir 11 (1995), S. 4474-4479 
    Details
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/la00011a048
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  • 10
    Electronic Resource
    Electronic Resource
    Preparative effects on the surface area and pore structure of microporous heteropoly oxometalates (1991)
    s.l. : American Chemical Society
    Langmuir 7 (1991), S. 2273-2278 
    Details
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/la00058a049
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