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  • 1
    Publication Date: 2011-04-23
    Description: Shallow Radar soundings from the Mars Reconnaissance Orbiter reveal a buried deposit of carbon dioxide (CO(2)) ice within the south polar layered deposits of Mars with a volume of 9500 to 12,500 cubic kilometers, about 30 times that previously estimated for the south pole residual cap. The deposit occurs within a stratigraphic unit that is uniquely marked by collapse features and other evidence of interior CO(2) volatile release. If released into the atmosphere at times of high obliquity, the CO(2) reservoir would increase the atmospheric mass by up to 80%, leading to more frequent and intense dust storms and to more regions where liquid water could persist without boiling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Phillips, Roger J -- Davis, Brian J -- Tanaka, Kenneth L -- Byrne, Shane -- Mellon, Michael T -- Putzig, Nathaniel E -- Haberle, Robert M -- Kahre, Melinda A -- Campbell, Bruce A -- Carter, Lynn M -- Smith, Isaac B -- Holt, John W -- Smrekar, Suzanne E -- Nunes, Daniel C -- Plaut, Jeffrey J -- Egan, Anthony F -- Titus, Timothy N -- Seu, Roberto -- New York, N.Y. -- Science. 2011 May 13;332(6031):838-41. doi: 10.1126/science.1203091. Epub 2011 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Planetary Science Directorate, Southwest Research Institute, Boulder, CO 80302, USA. roger@boulder.swri.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21512003" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere ; Carbon Dioxide ; Cold Temperature ; *Dry Ice ; Extraterrestrial Environment ; Ice ; *Mars ; Water
    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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  • 2
    Publication Date: 2013-03-09
    Description: Outflow channels on Mars are interpreted as the product of gigantic floods due to the catastrophic eruption of groundwater that may also have initiated episodes of climate change. Marte Vallis, the largest of the young martian outflow channels (〈500 million years old), is embayed by lava flows that hinder detailed studies and comparisons with older channel systems. Understanding Marte Vallis is essential to our assessment of recent Mars hydrologic activity during a period otherwise considered to be cold and dry. Using data from the Shallow Radar sounder on the Mars Reconnaissance Orbiter, we present a three-dimensional (3D) reconstruction of buried channels on Mars and provide estimates of paleohydrologic parameters. Our work shows that Cerberus Fossae provided the waters that carved Marte Vallis, and it extended an additional 180 kilometers to the east before the emplacement of the younger lava flows. We identified two stages of channel incision and determined that channel depths were more than twice those of previous estimates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morgan, Gareth A -- Campbell, Bruce A -- Carter, Lynn M -- Plaut, Jeffrey J -- Phillips, Roger J -- New York, N.Y. -- Science. 2013 May 3;340(6132):607-10. doi: 10.1126/science.1234787. Epub 2013 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Earth and Planetary Studies, Smithsonian Institution, Washington, DC, USA. morganga@si.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23470730" target="_blank"〉PubMed〈/a〉
    Keywords: Extraterrestrial Environment ; Floods ; *Mars ; Radar ; *Water
    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: 2018-12-04
    Description: There remains an urgent need for the noninvasive tracking of transfused chimeric antigen receptor (CAR) T cells to determine their biodistribution, viability, expansion, and antitumor functionality. DOTA antibody reporter 1 (DAbR1) comprises a single-chain fragment of the antilanthanoid-DOTA antibody 2D12.5/G54C fused to the human CD4-transmembrane domain and binds irreversibly to lanthanoid ( S )-2-(4-acrylamidobenzyl)-DOTA (AABD). The aim of this study was to investigate whether DAbR1 can be expressed on lymphocytes and used as a reporter gene as well as a suicide gene for therapy of immune-related adverse effects. Methods: DAbR1 was subcloned together with green fluorescent protein into an SFG-retroviral vector and used to transduce CD3/CD28-activated primary human T cells and second-generation 1928z (CAR) T cells. Cell surface expression of DAbR1 was confirmed by cell uptake studies with radiolabeled AABD. In addition, the feasibility of imaging of DAbR1-positive T cells in vivo after intravenous injection of 86 Y/ 177 Lu-AABD was studied and radiation doses determined. Results: A panel of DAbR1-expressing T cells and CAR T cells exhibited greater than 8-fold increased uptake of 86 Y-AABD in vitro when compared with nontransduced cells. Imaging studies showed 86 Y-AABD was retained by DAbR1-positive T cells while it continuously cleared from normal tissues, allowing for in vivo tracking of intravenously administered CAR T cells. Normal-organ dose estimates were favorable for repeated PET/CT studies. Selective T cell ablation in vivo with 177 Lu-AABD seems feasible for clustered T-cell populations. Conclusion: We have demonstrated for the first time that T cells can be modified with DAbR1, enabling their in vivo tracking via PET and SPECT. The favorable biodistribution and high image contrast observed warrant further studies of this new reporter gene.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 4
    Publication Date: 2018-08-03
    Description: The DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is overexpressed in glioblastoma, with overall low expression in healthy brain tissue. Paired with the availability of specific small molecule inhibitors, PARP-1 is a near-ideal target to develop novel radiotherapeutics to induce DNA damage and apoptosis in cancer cells, while sparing healthy brain tissue. Methods: We synthesized an 131 I-labeled PARP-1 therapeutic and investigated its pharmacology in vitro and in vivo. A subcutaneous tumor model was used to quantify retention times and therapeutic efficacy. A potential clinical scenario, intratumoral convection-enhanced delivery, was mimicked using an orthotopic glioblastoma model combined with an implanted osmotic pump system to study local administration of 131 I-PARPi (PARPi is PARP inhibitor). Results: 131 I-PARPi is a 1(2H)-phthalazinone, similar in structure to the Food and Drug Administration–approved PARP inhibitor AZD-2281. In vitro studies have shown that 131 I-PARPi and AZD-2281 share similar pharmacologic profiles. 131 I-PARPi delivered 134.1 cGy/MBq intratumoral injected activity. Doses to nontarget tissues, including liver and kidney, were significantly lower. Radiation damage and cell death in treated tumors were shown by p53 activation in U87-MG cells transfected with a p53-bioluminescent reporter. Treated mice showed significantly longer survival than mice receiving vehicle (29 vs. 22 d, P 〈 0.005) in a subcutaneous model. Convection-enhanced delivery demonstrated efficient retention of 131 I-PARPi in orthotopic brain tumors, while quickly clearing from healthy brain tissue. Conclusion: Our results demonstrate 131 I-PARPi’s high potential as a therapeutic and highlight PARP’s relevance as a target for radionuclide therapy. Radiation plays an integral role in brain tumor therapy, and radiolabeled PARP therapeutics could ultimately lead to improvements in the standard of care.
    Print ISSN: 0022-3123
    Topics: Medicine
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