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  • 1
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    The Amorphous Component in Martian Basaltic Soil in Global Perspective from MSL and MER Missions (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The mineralogy instrument CheMin onboard the MSL rover Curiosity analyzed by transmission XRD [1] the 〈150 microns size fraction of putative global basaltic martian soil from scoops 4 and 5 of the Rocknest aeolian bedform (sol 81-120). Here, we combine chemical (APXS) and mineralogical (Mossbauer; MB) results from the MER rovers with chemical (APXS) and mineralogical (CheMin) results from Curiosity to constrain the relative proportions of amorphous and crystalline components, the bulk chemical composition of those components, and the
    Keywords: Geophysics
    Type: JSC-CN-27902 , Lunar and Planetary Science Conference; Mar 08, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 2
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    First X-Ray Diffraction Results from Mars Science Laboratory: Mineralogy of Rocknest Aeolian Bedform at Gale Crater (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Numerous orbital and landed observations of the martian surface suggest a reasonably uniform martian soil composition, likely as a result of global aeolian mixing [1, 2]. Chemical data for martian soils are abundant [e.g., 2, 3], and phase information has been provided by lander thermal emission and Moessbauer spectroscopic measurements [3, 4, 5, 6]. However, until now no X-ray diffraction (XRD) data were available for martian soil nor has XRD ever been used on another body apart from Earth. XRD is generally considered the most definitive method for determining the crystalline phases in solid samples, and it is the method of choice for determining mineralogy. CheMin s first XRD analysis on Mars coincided with the 100th anniversary of the discovery of X-ray diffraction by von Laue. Curiosity delivered scooped samples of loose, unconsolidated material ("soil") acquired from an aeolian bedform at the Rocknest locality to instruments in the body of the rover (the laboratory). Imaging shows that the soil has a range of particle sizes, of 1-2 mm and smaller, presumably representing contributions from global, regional, and local sources.
    Keywords: Geophysics
    Type: JSC-CN-27878 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 3
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    Mineralogy and Elemental Composition of Wind Drift Soil at Rocknest, Gale Crater (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The Mars Science Laboratory rover Curiosity has been exploring Mars since August 5, 2012, conducting engineering and first-time activities with its mobility system, arm, sample acquisition and processing system (SA/SPaH-CHIMRA) and science instruments. Curiosity spent 54 sols at a location named "Rocknest," collecting and processing five scoops of loose, unconsolidated materials ("soil") acquired from an aeolian bedform (Fig. 1). The Chemistry and Mineralogy (CheMin) instrument analyzed portions of scoops 3, 4, and 5, to obtain the first quantitative mineralogical analysis of Mars soil, and to provide context for Sample Analysis at Mars (SAM) measurements of volatiles, isotopes and possible organic materials.
    Keywords: Geophysics
    Type: JSC-CN-27908 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 23, 2013; The Woodlands, TX; United States
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  • 4
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    Basaltic Soil of Gale Crater: Crystalline Component Compared to Martian Basalts and Meteorites (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: A significant portion of the soil of the Rocknest dune is crystalline and is consistent with derivation from unweathered basalt. Minerals and their compositions are identified by X-ray diffraction (XRD) data from the CheMin instrument on MSL Curiosity. Basalt minerals in the soil include plagioclase, olivine, low- and high-calcium pyroxenes, magnetite, ilmenite, and quartz. The only minerals unlikely to have formed in an unaltered basalt are hematite and anhydrite. The mineral proportions and compositions of the Rocknest soil are nearly identical to those of the Adirondack-class basalts of Gusev Crater, Mars, inferred from their bulk composition as analyzed by the MER Spirit rover.
    Keywords: Geophysics
    Type: JSC-CN-27905 , 44th Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 5
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    Crystal-Chemical Analysis of Soil at Rocknest, Gale Crater (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The CheMin instrument on the Mars Science Laboratory rover Curiosity performed X-ray diffraction analysis on Martian soil [1] at Rocknest in Gale Crater. In particular, crystalline phases from scoop 5 were identified and analyzed with the Rietveld method [2]. Refined unit-cell parameters are reported in Table 1. Comparing these unit-cell parameters with those in the literature provides an estimate of the chemical composition of the crystalline phases. For instance, Fig. 1 shows the Mg-content of Fa-Fo olivine as a function of the b unit-cell parameter using literature data. Our refined b parameter is indicated by the black triangle.
    Keywords: Geophysics
    Type: JSC-CN-27874 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 6
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    Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-11-15
    Description: Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic beta-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lloyd, David J -- St Jean, David J Jr -- Kurzeja, Robert J M -- Wahl, Robert C -- Michelsen, Klaus -- Cupples, Rod -- Chen, Michelle -- Wu, John -- Sivits, Glenn -- Helmering, Joan -- Komorowski, Renee -- Ashton, Kate S -- Pennington, Lewis D -- Fotsch, Christopher -- Vazir, Mukta -- Chen, Kui -- Chmait, Samer -- Zhang, Jiandong -- Liu, Longbin -- Norman, Mark H -- Andrews, Kristin L -- Bartberger, Michael D -- Van, Gwyneth -- Galbreath, Elizabeth J -- Vonderfecht, Steven L -- Wang, Minghan -- Jordan, Steven R -- Veniant, Murielle M -- Hale, Clarence -- England -- Nature. 2013 Dec 19;504(7480):437-40. doi: 10.1038/nature12724. Epub 2013 Nov 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Metabolic Disorders, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. ; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. ; Department of Comparative Biology & Safety Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24226772" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Blood Glucose/metabolism ; Carrier Proteins/*antagonists & inhibitors/metabolism ; Cell Nucleus/enzymology ; Crystallography, X-Ray ; Diabetes Mellitus, Type 2/blood/*drug therapy/enzymology ; Disease Models, Animal ; Hepatocytes ; Humans ; Hyperglycemia/blood/drug therapy/enzymology ; Hypoglycemic Agents/chemistry/*pharmacology/*therapeutic use ; Liver/cytology/enzymology/metabolism ; Male ; Models, Molecular ; Organ Specificity ; Phosphorylation/drug effects ; Piperazines/chemistry/metabolism/pharmacology/therapeutic use ; Protein Binding/drug effects ; Protein Transport/drug effects ; Rats ; Rats, Wistar ; Sulfonamides/chemistry/metabolism/pharmacology/therapeutic use
    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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  • 7
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    Targeting Plasmodium PI(4)K to eliminate malaria (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-11-29
    Description: Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940870/" 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/PMC3940870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, Case W -- Lee, Marcus C S -- Lim, Chek Shik -- Lim, Siau Hoi -- Roland, Jason -- Nagle, Advait -- Simon, Oliver -- Yeung, Bryan K S -- Chatterjee, Arnab K -- McCormack, Susan L -- Manary, Micah J -- Zeeman, Anne-Marie -- Dechering, Koen J -- Kumar, T R Santha -- Henrich, Philipp P -- Gagaring, Kerstin -- Ibanez, Maureen -- Kato, Nobutaka -- Kuhen, Kelli L -- Fischli, Christoph -- Rottmann, Matthias -- Plouffe, David M -- Bursulaya, Badry -- Meister, Stephan -- Rameh, Lucia -- Trappe, Joerg -- Haasen, Dorothea -- Timmerman, Martijn -- Sauerwein, Robert W -- Suwanarusk, Rossarin -- Russell, Bruce -- Renia, Laurent -- Nosten, Francois -- Tully, David C -- Kocken, Clemens H M -- Glynne, Richard J -- Bodenreider, Christophe -- Fidock, David A -- Diagana, Thierry T -- Winzeler, Elizabeth A -- 078285/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090534/Wellcome Trust/United Kingdom -- 096157/Wellcome Trust/United Kingdom -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI085584/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI103058/AI/NIAID NIH HHS/ -- R01079709/PHS HHS/ -- R01085584/PHS HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- WT096157/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Dec 12;504(7479):248-53. doi: 10.1038/nature12782. Epub 2013 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2]. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2]. ; Novartis Institutes for Tropical Disease, 138670 Singapore. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Parasitology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands. ; TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands. ; Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland. ; 1] Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland [2] University of Basel, CH-4003 Basel, Switzerland. ; Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts 02118, USA. ; Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. ; 1] TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands [2] Department of Medical Microbiology, Radboud University, Nijmegen Medical CentrePO Box 9101, 6500 HB Nijmegen, The Netherlands. ; Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore. ; 1] Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore [2] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 117545 Singapore. ; 1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK [2] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; 1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2] Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24284631" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Phosphatidylinositol 4-Kinase/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cytokinesis/drug effects ; Drug Resistance/drug effects/genetics ; Fatty Acids/metabolism ; Female ; Hepatocytes/parasitology ; Humans ; Imidazoles/metabolism/pharmacology ; Life Cycle Stages/drug effects ; Macaca mulatta ; Malaria/*drug therapy/*parasitology ; Male ; Models, Biological ; Models, Molecular ; Phosphatidylinositol Phosphates/metabolism ; Plasmodium/classification/*drug effects/*enzymology/growth & development ; Pyrazoles/metabolism/pharmacology ; Quinoxalines/metabolism/pharmacology ; Reproducibility of Results ; Schizonts/cytology/drug effects ; rab GTP-Binding Proteins/genetics/metabolism
    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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    Limited airborne transmission of H7N9 influenza A virus between ferrets (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-08-09
    Description: Wild waterfowl form the main reservoir of influenza A viruses, from which transmission occurs directly or indirectly to various secondary hosts, including humans. Direct avian-to-human transmission has been observed for viruses of subtypes A(H5N1), A(H7N2), A(H7N3), A(H7N7), A(H9N2) and A(H10N7) upon human exposure to poultry, but a lack of sustained human-to-human transmission has prevented these viruses from causing new pandemics. Recently, avian A(H7N9) viruses were transmitted to humans, causing severe respiratory disease and deaths in China. Because transmission via respiratory droplets and aerosols (hereafter referred to as airborne transmission) is the main route for efficient transmission between humans, it is important to gain an insight into airborne transmission of the A(H7N9) virus. Here we show that although the A/Anhui/1/2013 A(H7N9) virus harbours determinants associated with human adaptation and transmissibility between mammals, its airborne transmissibility in ferrets is limited, and it is intermediate between that of typical human and avian influenza viruses. Multiple A(H7N9) virus genetic variants were transmitted. Upon ferret passage, variants with higher avian receptor binding, higher pH of fusion, and lower thermostability were selected, potentially resulting in reduced transmissibility. This A(H7N9) virus outbreak highlights the need for increased understanding of the determinants of efficient airborne transmission of avian influenza viruses between mammals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819191/" 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/PMC3819191/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richard, Mathilde -- Schrauwen, Eefje J A -- de Graaf, Miranda -- Bestebroer, Theo M -- Spronken, Monique I J -- van Boheemen, Sander -- de Meulder, Dennis -- Lexmond, Pascal -- Linster, Martin -- Herfst, Sander -- Smith, Derek J -- van den Brand, Judith M -- Burke, David F -- Kuiken, Thijs -- Rimmelzwaan, Guus F -- Osterhaus, Albert D M E -- Fouchier, Ron A M -- HHSN266200700010C/AI/NIAID NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- England -- Nature. 2013 Sep 26;501(7468):560-3. doi: 10.1038/nature12476. Epub 2013 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Viroscience, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925116" target="_blank"〉PubMed〈/a〉
    Keywords: Air Microbiology ; Animals ; Birds/virology ; Cercopithecus aethiops ; Dogs ; Ferrets/*virology ; Genome, Viral/genetics ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Humans ; Influenza A virus/chemistry/classification/genetics/*pathogenicity ; Influenza in Birds/transmission/virology ; Influenza, Human/transmission/virology ; Madin Darby Canine Kidney Cells ; Models, Molecular ; Orthomyxoviridae Infections/*transmission/*virology ; Vero Cells
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Possible Detection of Nitrates on Mars by the Sample Analysis at Mars (SAM) Instrument (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Planetary models suggest that nitrogen was abundant in the early Martian atmosphere as dinitrogen (N2). However, it has been lost by sputtering and photochemical loss to space [1, 2], impact erosion [3], and chemical oxidation to nitrates [4]. Nitrates, produced early in Mars history, are later decomposed back into N2 by the current impact flux [5], making possible a nitrogen cycle on Mars. It is estimated that a layer of about 3 m of pure NaNO3 should be distributed globally on Mars [5]. Nitrates are a fundamental source for nitrogen to terrestrial microorganisms. Therefore, the detection of soil nitrates is important to assess habitability in the Martian environment. The only previous mission that was designed to search for soil nitrates was the Phoenix mission but was unable to detect evolved N-containing species by TEGA and the MECA WCL [6]. Nitrates have been tentatively identified in the Nakhla meteorite [7]. The purpose of this work is to determine if nitrates were detected in first solid sample (Rocknest) in Gale Crater examined by the SAM instrument.
    Keywords: Geophysics
    Type: JSC-CN-28000 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 10
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    Insights into the Sulfur Mineralogy of Martian Soil at Rocknest, Gale Crater, Enabled by Evolved Gas Analyses (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: The first solid samples analysed by the Chemistry and Mineralogy (CheMin) instrument and Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) consisted of 〈 150 m fines sieved from aeolian bedform material at a site named Rocknest. All four samples of this material analyzed by SAM s evolved gas analysis mass spectrometry (EGA-MS) released H2O, CO2, O2, and SO2 (Fig. 1), as well as H2S and possibly NO. This is the first time evolved SO2 (and evolved H2S) has been detected from thermal analysis of martian materials. The identity of these evolved gases and temperature (T) of evolution can support mineral detection by CheMin and place constraints on trace volatile-bearing phases present below the CheMin detection limit or difficult to characterize with XRD (e.g., X-ray amorphous phases). Constraints on phases responsible for evolved CO2 and O2 are detailed elsewhere [1,2,3]. Here, we focus on potential constraints on phases that evolved SO2, H2S, and H2O during thermal analysis.
    Keywords: Geophysics
    Type: JSC-CN-27926 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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