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  • 1
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    Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-09-23
    Description: The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Z -- Huang, P L -- Panahian, N -- Dalkara, T -- Fishman, M C -- Moskowitz, M A -- NS10828/NS/NINDS NIH HHS/ -- NS2636/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1994 Sep 23;265(5180):1883-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stroke Research Laboratory, Massachusetts General Hospital, Charlestown 02129.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7522345" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/antagonists & inhibitors/deficiency/*metabolism ; Animals ; Arginine/analogs & derivatives/pharmacology ; Brain/enzymology/*metabolism ; Brain Ischemia/complications/*metabolism ; Cerebral Infarction/*etiology ; Cerebrovascular Circulation ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Neurons/*enzymology ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase ; Nitroarginine
    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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  • 2
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    Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-07-22
    Description: Long-term potentiation (LTP) is a persistent increase in synaptic strength implicated in certain forms of learning and memory. In the CA1 region of the hippocampus, LTP is thought to involve the release of one or more retrograde messengers from the postsynaptic cell that act on the presynaptic terminal to enhance transmitter release. One candidate retrograde messenger is the membrane-permeant gas nitric oxide (NO), which in the brain is released after activation of the neuronal-specific NO synthase isoform (nNOS). To assess the importance of NO in hippocampal synaptic plasticity, LTP was examined in mice where the gene encoding nNOS was disrupted by gene targeting. In nNOS- mice, LTP induced by weak intensity tetanic stimulation was normal except for a slight reduction in comparison to that in wild-type mice and was blocked by NOS inhibitors, just as it was in wild-type mice. Immunocytochemical studies indicate that in the nNOS- mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1 neurons. These findings suggest that eNOS, rather than nNOS, generates NO within the postsynaptic cell during LTP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Dell, T J -- Huang, P L -- Dawson, T M -- Dinerman, J L -- Snyder, S H -- Kandel, E R -- Fishman, M C -- DA-00074/DA/NIDA NIH HHS/ -- DA-00266/DA/NIDA NIH HHS/ -- MH-45923/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1994 Jul 22;265(5171):542-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7518615" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/antagonists & inhibitors/genetics/*metabolism ; Animals ; Arginine/*analogs & derivatives/pharmacology ; Electric Stimulation ; Endothelium/enzymology ; Hippocampus/drug effects/enzymology/*physiology ; In Vitro Techniques ; *Long-Term Potentiation/drug effects ; Mice ; Mutation ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase ; Nitroarginine ; Pyramidal Cells/drug effects/enzymology/*physiology ; Synaptic Transmission/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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  • 3
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    CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-03-26
    Description: Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406187/" 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/PMC3406187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beatty, Gregory L -- Chiorean, Elena G -- Fishman, Matthew P -- Saboury, Babak -- Teitelbaum, Ursina R -- Sun, Weijing -- Huhn, Richard D -- Song, Wenru -- Li, Dongguang -- Sharp, Leslie L -- Torigian, Drew A -- O'Dwyer, Peter J -- Vonderheide, Robert H -- K08 CA138907/CA/NCI NIH HHS/ -- K12 CA076931/CA/NCI NIH HHS/ -- P30 CA016520/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1612-6. doi: 10.1126/science.1198443.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436454" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Animals ; Antibodies, Monoclonal/administration & dosage/adverse ; effects/metabolism/*therapeutic use ; Antigens, CD40/*agonists/*immunology ; Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/immunology/pathology/secondary ; Deoxycytidine/analogs & derivatives/therapeutic use ; Disease Models, Animal ; Disease-Free Survival ; Female ; Humans ; Immunologic Surveillance ; Macrophage Activation ; Macrophages/immunology ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/immunology/pathology ; T-Lymphocytes/immunology ; Tumor Microenvironment ; Young Adult
    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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    GBM Observations of Terrestrial Gamma-Ray Flashes (2010)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: The TGF detection rate of Gamma-ray Burst Monitor (GBM) has been increased twice since launch. The most recent improvement is from a new operating mode in which data for individual photons are down-linked for selected portions of the orbit, enabling a more sensitive ground-based search for TGFs. The new search has increased the TGF detection rate and is finding TGFs more than five times fainter than the TGFs of the previous GBM sample. We summarize the properties of the original GBM TGF sample and compare to the less intense TGFs now being detected. In addition to gamma-ray TGFs, GBM is observing distant TGFs from the propagation of charged particles along geomagnetic field lines. Strong 511 keV annihilation lines have been observed, demonstrating that both electrons and positrons are present in the particle beams. Spectral fits to these electron/positron TGFs will be shown.
    Keywords: Astronomy
    Type: M11-0072 , 2010 American Geophysical Union (AGU) Fall Meeting; Dec 13, 2010 - Dec 17, 2010; San Francisco, CA; United States
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  • 5
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    What Can Geolocated Sferics Tell Us About Terrestrial Gamma-Ray Flashes? (2010)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: The Fermi Gamma-ray Burst Monitor (GBM) has been detecting TGFs with increasing sensitivity over the past two years, owing to changes in flight software that have lowered its threshold for triggering and, recently, allowed a search for TGFs weaker than those which would cause an onboard trigger. Associations between TGFs detected in the first 18 months of operation and sferics detected using the World Wide Lightning Location Network (WWLLN) show that TGF peaks and lightning discharges are simultaneous to within tens of microseconds, and that GBM triggered on TGFs that occurred up to a distance of 300 km from the sub-spacecraft position. In the work presented here, we look for associations between TGFs detected by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and WWLLN sferics over the same 18 months, and we compare the match rate and detection horizon of the two instruments. We also look for associations between WWLLN sferics and more recent GBM TGFs, both triggered events and weaker TGFs uncovered in our untriggered search. We discuss whether in this new mode, GBM is detecting TGFs that are more distant from the sub-spacecraft point than 300 km, or whether the weaker TGFs are instead indicative of a luminosity distribution, either because the weaker ones originate deeper in the atmosphere or because they are intrinsically dimmer.
    Keywords: Astronomy
    Type: M11-0038 , 2010 American Geophysical Union (AGU) Fall Meeting; Dec 13, 2010 - Dec 17, 2010; San Francisco, CA; United States
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  • 6
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    The Latest Space-Borne Observations of TGFs from Fermi-GBM (2010)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: The Gamma-ray Burst Monitor (GBM) on the Fermi Gamma-ray Space Telescope Observatory (Fermi) is detecting about two TGFs per week. This rate has increased by a factor of approx.eight since launch when flight software was uploaded to the spacecraft in November 2009 in order to increase the sensitivity of GBM to TGFs. Weaker, un-triggered TGFs are now also being observed about once per day over selected low-latitude regions Americas. The high efficiency and time resolution (2 s) of GBM allows temporal features to be resolved so that some insight may be gained on the origin and transport of the gamma-ray photons through the atmosphere. TGFs are observed to be shorter than previously thought, with an average duration of approx.100 micro-s. The absolute times of TGFs are known to approx.10 micro-s, allowing accurate correlations of TGFs with lightning networks and other lightning-related phenomena. The events are observed in the thick bismuth germanate (BGO) scintillation detectors of GBM with photon energies above 40 MeV. Other new results on the temporal and spectral characteristics of TGFs will be presented, along with properties of several electron-positron TGF events that have been identified.
    Keywords: Astronomy
    Type: M10-1059 , E-CANE-ASIM Workshop on TLE''s and TGF''s; Oct 25, 2010 - Oct 27, 2010; Amsterdam; Netherlands
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  • 7
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    BATSE: The History and Legacy (2012)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: No abstract available
    Keywords: Astronomy
    Type: M12-2163 , Gamma Ray Burst (GRM) Symposium/Instituto de Astrofisica de Andalucia (IAA-CSIC) and the Dept. of Sys. Eng. and Automation (ISA-UMA); Oct 08, 2012 - Oct 12, 2012; Marbella; Spain
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  • 8
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    BATSE - The History and Legacy (2012)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: No abstract available
    Keywords: Astronomy
    Type: M12-1766 , Gamma-ray Bursts 2012 Conference; May 07, 2012 - May 11, 2012; Munich; Germany
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  • 9
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    Terrestrial Gamma-Ray Flashes (TGFs) Above Thunderstorms (2012)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Intense of gamma rays have been observed by five different space-borne detectors. The TGFs have hard spectra, with photons extending to over 50 MeV. Most of these flashes last less than a millisecond. Relativistic electrons and positrons associated with TGFs are also seen by orbiting instruments In a special mode of operation, the Fermi-GBM detectors are now detecting an average of about one TGF every two hours. The Fermi spacecraft has been performing special orientations this year which has allowed the Fermi-LAT instrument also detect TGFs. The most likely origin of these high energy photons is bremsstrahlung radiation from electrons, produced by relativistic runaway electrons in intense electric fields within or above thunderstorm regions; the altitude of origin is uncertain. These TGFs may produce an appreciable radiation dose to passengers and crew in nearby aircraft. The observational aspects of TGFs will be the main focus of this talk; theoretical aspects remain speculative.
    Keywords: Astronomy
    Type: M12-1497 , M12-1551 , 2012 American Association for the Advancement of Science (AAAS) Annual Meeting; Feb 16, 2012 - Feb 20, 2012; Vancouver; Canada
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  • 10
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    Gamma-Ray Bursts (2012)
    In:  CASI
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    Publication Date: 2019-07-12
    Description: No abstract available
    Keywords: Astronomy
    Type: M12-1671
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