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  • 1
    Publication Date: 2011-04-14
    Description: The fate of deepwater releases of gas and oil mixtures is initially determined by solubility and volatility of individual hydrocarbon species; these attributes determine partitioning between air and water. Quantifying this partitioning is necessary to constrain simulations of gas and oil transport, to predict marine bioavailability of different fractions of the gas-oil mixture, and to develop a comprehensive picture of the fate of leaked hydrocarbons in the marine environment. Analysis of airborne atmospheric data shows massive amounts (∼258,000 kg/day) of hydrocarbons evaporating promptly from the Deepwater Horizon spill; these data collected during two research flights constrain air-water partitioning, thus bioavailability and fate, of the leaked fluid. This analysis quantifies the fraction of surfacing hydrocarbons that dissolves in the water column (∼33% by mass), the fraction that does not dissolve, and the fraction that evaporates promptly after surfacing (∼14% by mass). We do not quantify the leaked fraction lacking a surface expression; therefore, calculation of atmospheric mass fluxes provides a lower limit to the total hydrocarbon leak rate of 32,600 to 47,700 barrels of fluid per day, depending on reservoir fluid composition information. This study demonstrates a new approach for rapid-response airborne assessment of future oil spills.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 2
    Publication Date: 2012-11-27
    Description: The sea breeze/land breeze diurnal circulation within the Los Angeles Basin and adjacent waters transports marine air into the basin during the day and urban air to Santa Monica Bay during the night. Nitryl chloride, ClNO2 is a nocturnal trace gas formed from the heterogeneous reaction of dinitrogen pentaoxide (N2O5) with chloride containing aerosol. Its photolysis after sunrise produces atomic chlorine radicals and regenerates NO2, both of which may increase ozone production. Mixing of the chloride source from marine sea salt with the urban NOx source in Los Angeles provides conditions ideal for the production of ClNO2. This paper presents an analysis using a wind profiler on the coast and measurements of ClNO2 and its precursors made from both ship and aircraft to assess the prevailing meteorological conditions important for ClNO2 production in this region, with a particular focus on the production over water within the land breeze phase of the circulation. A box model is used to calculate an upper limit to the amount of ClNO2 capable of being produced strictly over Santa Monica Bay during the land breeze. On three out of the four nights of ClNO2 measurements in Santa Monica Bay, the ClNO2 exceeds the upper limit calculated using the box model and shows that the majority of the ClNO2 is produced over the city and transported to Santa Monica Bay by the land breeze. This ClNO2 transport suggests the sea breeze more efficiently transports aerosol chloride inland than land breeze transports NOx offshore.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
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    In:  J. Fluid Mech., New York, August, vol. 62, no. 3-4, pp. 465-538, pp. 1610, (ISSN: 1340-4202)
    Publication Date: 1974
    Keywords: ConvolutionE ; Modelling
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  • 4
    Publication Date: 2013-08-31
    Description: [1]  The nocturnal conversion of dinitrogen pentoxide (N 2 O 5 ) to nitryl chloride (ClNO 2 ) on chloride-containing aerosol can be a regionally important NO x (= NO + NO 2 ) recycling and halogen activation pathway that affects oxidant photochemistry the following day. Here, we present a comprehensive measurement data set acquired at Pasadena, California, during the CalNex-LA campaign 2010 that included measurements of odd nitrogen and its major components (NO y  = NO x  + NO 3  + 2N 2 O 5  + ClNO 2  + HNO 3  + HONO + peroxyacyl, alkyl, and aerosol nitrates) and aerosol size distribution and composition. Nitryl chloride was present during every night of the study (median mixing ratio at sunrise 800 pptv) and was usually a more significant nocturnal NO x and odd oxygen (O x  = O 3  + NO 2  + 3N 2 O 5  + ClNO 2 ) reservoir species than N 2 O 5 (whose concentrations were calculated from its equilibrium with NO 2 and NO 3 ). At sunrise, ClNO 2 accounted for 21% of NO z (= NO y - NO x ), 4% of NO y , and 2.5% of O x , respectively (median values). Kinetic parameters for the N 2 O 5 to ClNO 2 conversion were estimated by relating ClNO 2 concentrations to their time-integrated heterogeneous production from N 2 O 5 and were highly variable between nights. Production of ClNO 2 required conversion of N 2 O 5 on submicron aerosol with average yield (ϕ) and N 2 O 5 reactive uptake probability (γ) of γϕ = 0.008 (maximum 0.04), scaled with submicron aerosol chloride content, and was suppressed by aerosol organic matter and liquid water content. Not all of the observed variability of ClNO 2 production efficiency could be rationalized using current literature parameterizations.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 5
    Publication Date: 2012-07-22
    Description: Environmental Science & Technology DOI: 10.1021/es301691k
    Print ISSN: 0013-936X
    Electronic ISSN: 1520-5851
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
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  • 6
    Publication Date: 2012-05-11
    Description: Ozone (O3), alkyl nitrates (RONO2), and other photochemical products were formed in the atmosphere downwind from the Deepwater Horizon (DWH) oil spill by photochemical reactions of evaporating hydrocarbons with NOx (=NO + NO2) emissions from spill response activities. Reactive nitrogen species and volatile organic compounds (VOCs) were measured from an instrumented aircraft during daytime flights in the marine boundary layer downwind from the area of surfacing oil. A unique VOC mixture, where alkanes dominated the hydroxyl radical (OH) loss rate, was emitted into a clean marine environment, enabling a focused examination of O3 and RONO2 formation processes. In the atmospheric plume from DWH, the OH loss rate, an indicator of potential O3 formation, was large and dominated by alkanes with between 5 and 10 carbons per molecule (C5–C10). Observations showed that NOx was oxidized very rapidly with a 0.8 h lifetime, producing primarily C6–C10 RONO2 that accounted for 78% of the reactive nitrogen enhancements in the atmospheric plume 2.5 h downwind from DWH. Both observations and calculations of RONO2 and O3 production rates show that alkane oxidation dominated O3 formation chemistry in the plume. Rapid and nearly complete oxidation of NOx to RONO2 effectively terminated O3 production, with O3 formation yields of 6.0 ± 0.5 ppbv O3 per ppbv of NOx oxidized. VOC mixing ratios were in large excess of NOx, and additional NOx would have formed additional O3 in this plume. Analysis of measurements of VOCs, O3, and reactive nitrogen species and calculations of O3 and RONO2 production rates demonstrate that NOx-VOC chemistry in the DWH plume is explained by known mechanisms.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 7
    Publication Date: 2010-03-27
    Description: Tumor manipulation of host immunity is important for tumor survival and invasion. Many cancers secrete CCL21, a chemoattractant for various leukocytes and lymphoid tissue inducer cells, which drive lymphoid neogenesis. CCL21 expression by melanoma tumors in mice was associated with an immunotolerant microenvironment, which included the induction of lymphoid-like reticular stromal networks, an altered cytokine milieu, and the recruitment of regulatory leukocyte populations. In contrast, CCL21-deficient tumors induced antigen-specific immunity. CCL21-mediated immune tolerance was dependent on host rather than tumor expression of the CCL21 receptor, CCR7, and could protect distant, coimplanted CCL21-deficient tumors and even nonsyngeneic allografts from rejection. We suggest that by altering the tumor microenvironment, CCL21-secreting tumors shift the host immune response from immunogenic to tolerogenic, which facilitates tumor progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shields, Jacqueline D -- Kourtis, Iraklis C -- Tomei, Alice A -- Roberts, Joanna M -- Swartz, Melody A -- New York, N.Y. -- Science. 2010 May 7;328(5979):749-52. doi: 10.1126/science.1185837. Epub 2010 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line, Tumor ; Chemokine CCL21/*metabolism ; Cytokines/metabolism ; Disease Progression ; Female ; Immune Tolerance ; Lymph Nodes/immunology ; Lymphoid Tissue/*immunology/pathology ; Melanoma, Experimental/*immunology/*pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; RNA Interference ; Receptors, CCR7/metabolism ; Signal Transduction ; Stromal Cells/*immunology/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/immunology ; *Tumor Escape
    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: 2016-01-07
    Description: Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shu, Shaokun -- Lin, Charles Y -- He, Housheng Hansen -- Witwicki, Robert M -- Tabassum, Doris P -- Roberts, Justin M -- Janiszewska, Michalina -- Huh, Sung Jin -- Liang, Yi -- Ryan, Jeremy -- Doherty, Ernest -- Mohammed, Hisham -- Guo, Hao -- Stover, Daniel G -- Ekram, Muhammad B -- Peluffo, Guillermo -- Brown, Jonathan -- D'Santos, Clive -- Krop, Ian E -- Dillon, Deborah -- McKeown, Michael -- Ott, Christopher -- Qi, Jun -- Ni, Min -- Rao, Prakash K -- Duarte, Melissa -- Wu, Shwu-Yuan -- Chiang, Cheng-Ming -- Anders, Lars -- Young, Richard A -- Winer, Eric P -- Letai, Antony -- Barry, William T -- Carroll, Jason S -- Long, Henry W -- Brown, Myles -- Liu, X Shirley -- Meyer, Clifford A -- Bradner, James E -- Polyak, Kornelia -- CA080111/CA/NCI NIH HHS/ -- CA103867/CA/NCI NIH HHS/ -- CA120184/CA/NCI NIH HHS/ -- CA168504/CA/NCI NIH HHS/ -- P50 CA168504/CA/NCI NIH HHS/ -- R01 CA103867/CA/NCI NIH HHS/ -- England -- Nature. 2016 Jan 21;529(7586):413-7. doi: 10.1038/nature16508. Epub 2016 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; Department of Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Princess Margaret Cancer Center/University Health Network, Toronto, Ontario M5G1L7, Canada. ; Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G2M9, Canada. ; Harvard University, Cambridge, Massachusetts 02138, USA. ; Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK. ; Department of Pathology, Brigham and Women's Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; Simmons Comprehensive Cancer Center, Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ; Broad Institute, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26735014" 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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  • 9
    Publication Date: 2015-05-23
    Description: The development of effective pharmacological inhibitors of multidomain scaffold proteins, notably transcription factors, is a particularly challenging problem. In part, this is because many small-molecule antagonists disrupt the activity of only one domain in the target protein. We devised a chemical strategy that promotes ligand-dependent target protein degradation using as an example the transcriptional coactivator BRD4, a protein critical for cancer cell growth and survival. We appended a competitive antagonist of BET bromodomains to a phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex. The resultant compound, dBET1, induced highly selective cereblon-dependent BET protein degradation in vitro and in vivo and delayed leukemia progression in mice. A second series of probes resulted in selective degradation of the cytosolic protein FKBP12. This chemical strategy for controlling target protein stability may have implications for therapeutically targeting previously intractable proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winter, Georg E -- Buckley, Dennis L -- Paulk, Joshiawa -- Roberts, Justin M -- Souza, Amanda -- Dhe-Paganon, Sirano -- Bradner, James E -- P01 CA066996/CA/NCI NIH HHS/ -- P01-CA066996/CA/NCI NIH HHS/ -- R01-CA176745/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):1376-81. doi: 10.1126/science.aab1433. Epub 2015 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. james_bradner@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999370" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Azepines/chemistry/*pharmacology/therapeutic use ; Cell Line, Tumor ; Crystallography, X-Ray ; Disease Models, Animal ; *Drug Design ; Leukemia, Promyelocytic, Acute/drug therapy ; Ligands ; Mice ; Molecular Targeted Therapy ; Nuclear Proteins/antagonists & inhibitors/chemistry/*metabolism ; Peptide Hydrolases/*metabolism ; Phthalimides/*chemistry ; Protein Stability/drug effects ; Protein Structure, Tertiary ; Proteolysis/*drug effects ; Tacrolimus Binding Protein 1A/metabolism ; Thalidomide/*analogs & derivatives/chemistry/pharmacology/therapeutic use ; Transcription Factors/antagonists & inhibitors/chemistry/*metabolism ; Ubiquitin-Protein Ligases/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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  • 10
    Publication Date: 2006-04-29
    Description: Coral reefs are generally associated with shallow tropical seas; however, recent deep-ocean exploration using advanced acoustics and submersibles has revealed unexpectedly widespread and diverse coral ecosystems in deep waters on continental shelves, slopes, seamounts, and ridge systems around the world. Advances reviewed here include the use of corals as paleoclimatic archives and their biogeological functioning, biodiversity, and biogeography. Threats to these fragile, long-lived, and rich ecosystems are mounting: The impacts of deep-water trawling are already widespread, and effects of ocean acidification are potentially devastating.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, J Murray -- Wheeler, Andrew J -- Freiwald, Andre -- New York, N.Y. -- Science. 2006 Apr 28;312(5773):543-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll, PA37 1QA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16645087" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anthozoa/growth & development ; *Biodiversity ; Climate ; *Cold Temperature ; Conservation of Natural Resources ; *Ecosystem ; Environment ; Fishes ; Genetics, Population ; Geologic Sediments ; Hydrogen-Ion Concentration ; *Seawater ; Time
    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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