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- Title
- Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential.
- Creator
- Lohmueller, Jason J., Sato, Shuji, Popova, Lana, Chu, Isabel M., Tucker, Meghan A., Barberena, Roberto, Innocenti, Gregory M., Cudic, Mare, Ham, James D., Cheung, Wan Cheung, Polakiewicz, Roberto D., Finn, Olivera J.
- Abstract/Description
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MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a...
Show moreMUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1+ target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs.
Show less - Date Issued
- 2016-10-22
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000012
- Format
- Citation
- Title
- Antioptimization of earthquake exitation and response.
- Creator
- Zuccaro, G., Elishakoff, Isaac, Baratta, A.
- Abstract/Description
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The paper presents a novel approach to predict the response of earthquake-excited structures. The earthquake excitation is expanded in terms of series of deterministic functions. The coefficients of the series are represented as a point in N-dimensional space. Each available accelerogram at a certain site is then represented as a point in the above space, modeling the available fragmentary historical data. The minimum volume ellipsoid, containing all points, is constructed. The ellipsoidal...
Show moreThe paper presents a novel approach to predict the response of earthquake-excited structures. The earthquake excitation is expanded in terms of series of deterministic functions. The coefficients of the series are represented as a point in N-dimensional space. Each available accelerogram at a certain site is then represented as a point in the above space, modeling the available fragmentary historical data. The minimum volume ellipsoid, containing all points, is constructed. The ellipsoidal models of uncertainty, pertinent to earthquake excitation, are developed. The maximum response of a structure, subjected to the earthquake excitation, within ellipsoidal modeling of the latter, is determined. This procedure of determining least favorable response was termed in the literature (Elishakoff, 1991) as an antioptimization. It appears that under inherent uncertainty of earthquake excitation, antioptimization analysis is a viable alternative to stochastic approach.
Show less - Date Issued
- 1998
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000014
- Format
- Citation
- Title
- Antiviral Activity of Metal-Containing Polymers—Organotin and Cisplatin-Like Polymers.
- Creator
- Roner, Michael R., Carraher, Charles E., Shahi, Kimberly, Barot, Girish
- Abstract/Description
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Polymers containing platinum and to a lesser extent tin, have repeatedly demonstrated antitumor activity in vitro and in vivo against a variety of cell and tumor types. The mechanisms responsible for the antitumor activity include inducing a delay in cell proliferation and sister chromatid exchanges blocking tumor growth. As most DNA and some RNA viruses require, and even induce, infected cells to initiate DNA replication and subsequent cell division, compounds with antitumor activity will...
Show morePolymers containing platinum and to a lesser extent tin, have repeatedly demonstrated antitumor activity in vitro and in vivo against a variety of cell and tumor types. The mechanisms responsible for the antitumor activity include inducing a delay in cell proliferation and sister chromatid exchanges blocking tumor growth. As most DNA and some RNA viruses require, and even induce, infected cells to initiate DNA replication and subsequent cell division, compounds with antitumor activity will very likely also possess antiviral activity. This article examines the use of metal-containing polymers as a novel class of antivirals.
Show less - Date Issued
- 2011-05-27
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000008
- Format
- Citation
- Title
- Antonio Ruiz de Montoya, Apostle of the Guaraní.
- Creator
- Ganson, Barbara
- Abstract/Description
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This essay highlights the accomplishments of one of the foremost Jesuit missionaries in seventeenth-century Paraguay, Antonio Ruiz de Montoya. Born in Lima, Montoya distinguished himself as a chronicler of the first encounters between the Jesuits and the Guaraní Indians of South America. He defended Indian rights by speaking out against Indian slavery. Montoya spent approximately twenty-five years among the Guaraní indigenous peoples who influenced his worldview and sense of spirituality,...
Show moreThis essay highlights the accomplishments of one of the foremost Jesuit missionaries in seventeenth-century Paraguay, Antonio Ruiz de Montoya. Born in Lima, Montoya distinguished himself as a chronicler of the first encounters between the Jesuits and the Guaraní Indians of South America. He defended Indian rights by speaking out against Indian slavery. Montoya spent approximately twenty-five years among the Guaraní indigenous peoples who influenced his worldview and sense of spirituality, which are reflected in his 1636 first account of the Jesuit reducciones in Paraguay, Conquista espiritual hecha por los religiosos de la Compañía de Jesús en las provincias del Paraguay, Paraná, Uruguay, y Tapé.
Show less - Date Issued
- 2016-03-01
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000019
- Format
- Citation
- Title
- Ants (Hymenoptera: Formicidae) of Bermuda.
- Creator
- Wetterer, James K., Wetterer, Andrea L.
- Date Issued
- 2004-06
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000204
- Format
- Citation
- Title
- ANTS (HYMENOPTERA: FORMICIDAE) OF THE DRY TORTUGAS, THE OUTERMOST FLORIDA KEYS.
- Creator
- Wetterer, James K., O’Hara, Brandon C.
- Date Issued
- 2002-06
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000202
- Format
- Citation
- Title
- Ants (Hymenoptera: Formicidae) on Non-native Neotropical Ant-acacias (Fabales: Fabaceae) in Florida.
- Creator
- Wetterer, James K., Wetterer, Andrea L.
- Date Issued
- 2003-12
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000203
- Format
- Citation
- Title
- Assessing Potential Impacts of Sea Level Rise on Public Health and Vulnerable Populations in Southeast Florida and Providing a Framework to Improve Outcomes.
- Creator
- Bloetscher, Frederick, Polsky, Colin, Bolter, Keren P., Mitsova, Diana, Garces, Kristin, King, Roderick, Carballo, Isabel, Hamilton, Karen
- Date Issued
- 2016-03-31
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000110
- Format
- Citation
- Title
- Association of postfire peat accumulation and microtopography in boreal bogs.
- Creator
- Benscoter, Brian W, Vitt, Dale H, Wieder, R Kelman
- Date Issued
- 2005-09-01
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1139_x05-115_1632245551
- Format
- Citation
- Title
- Automatic classification of communication logs into implementation stages via text analysis.
- Creator
- Wang, Dingding, Ogihara, Mitsunori, Gallo, Carlos, Villamar, Juan A., Smith, Justin D., Vermeer, Wouter, Cruden, Gracelyn, Benbow, Nanette, Brown, C. Hendricks
- Date Issued
- 2015-12-06
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000198
- Format
- Citation
- Title
- Beyond the blank slate: routes to learning new coordination patterns depend on the intrinsic dynamics of the learner—experimental evidence and theoretical model.
- Creator
- Kostrubiec, Viviane, Zanone, Pier-Giorgio, Fuchs, Armin, Kelso, J. A. Scott
- Date Issued
- 2012
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000163
- Format
- Citation
- Title
- Bidirectional Coupling between Astrocytes and Neurons Mediates Learning and Dynamic Coordination in the Brain: A Multiple Modeling Approach.
- Creator
- Wade, John J., McDaid, Liam J., Harkin, Jim, Crunelli, Vincenzo, Kelso, J. A. Scott, Cymbalyuk, Gennady
- Abstract/Description
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In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model) which yields...
Show moreIn recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model) which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a ‘‘learning signal’’ to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity), and the modeling strategy may be extended to coordination among remote neuron clusters.
Show less - Date Issued
- 2011-12-29
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000027
- Format
- Citation
- Title
- Big data driven co-occurring evidence discovery in chronic obstructive pulmonary disease patients.
- Creator
- Baechle, Christopher, Agarwal, Ankur, Zhu, Xingquan
- Date Issued
- 2017-12-04
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1186_s40537-017-0067-6_1629211082
- Format
- Citation
- Title
- Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity.
- Creator
- Cerofolini, Linda, Amar, Sabrina, Lauer, Janelle L., Martelli, Tommaso, Fragai, Marco, Luchinat, Claudio, Fields, Gregg B.
- Abstract/Description
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Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple...
Show moreCell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain. Examination of simultaneous membrane interaction and triple-helix binding revealed a possible regulation of proteolysis due to steric effects of the membrane. At bicelle concentrations of 1%, enzymatic activity towards triple-helices was increased 1.5-fold. A single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) resulted in lower enzyme activation by bicelles. An initial structural framework has thus been developed to define the role(s) of cell membranes in modulating proteolysis.
Show less - Date Issued
- 2016-09-13
- PURL
- http://purl.flvc.org/fau/fd/FAUIR0000004
- Format
- Citation
- Title
- Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire: an expert assessment.
- Creator
- Abbott, Benjamin W., Jones, Jeremy B., Schuur, Edward A. G., Chapin III, F. Stuart, Bowden, William B., Bret-Harte, M. Syndonia, Epstein, Howard E., Flannigan, Michael D., Harms, Tamara K., Hollingsworth, Teresa N., Mack, Michelle C., McGuire, A. David, Natali, Susan M., Rocha, Adrian V., Tank, Suzanne E., Turetsky, Merritt R., Vonk, Jorien E., Wickland, Kimberly P., Aiken, George R., Alexander, Heather D., Amon, Rainer M. W., Benscoter, Brian, Bergeron, Yves, Bishop, Kevin, Blarquez, Olivier, Bond-Lamberty, Ben, Breen, Amy L., Buffam, Ishi, Cai, Yihua, Carcaillet, Christopher, Carey, Sean K., Chen, Jing M., Chen, Han Y. H., Christensen, Torben R., Cooper, Lee W., Cornelissen, J. Hans C., de Groot, William J., DeLuca, Thomas H., Dorrepaal, Ellen, Fetcher, Ned, Finlay, Jacques C., Forbes, Bruce C., French, Nancy H. F., Gauthier, Sylvie, Girardin, Martin P., Goetz, Scott J., Goldammer, Johann G., Gough, Laura, Grogan, Paul, Guo, Laodong, Higuera, Philip E., Hinzman, Larry, Hu, Feng Sheng, Hugelius, Gustaf, Jafarov, Elchin E., Jandt, Randi, Johnstone, Jill F., Jan Karlsson, Kasischke, Eric S., Kattner, Gerhard, Kelly, Ryan, Keuper, Frida, Kling, George W., Kortelainen, Pirkko, Kouki, Jari, Kuhry, Peter, Laudon, Hjalmar, Laurion, Isabelle, Macdonald, Robie W., Mann, Paul J., Martikainen, Pertti J., McClelland, James W., Molau, Ulf, Oberbauer, Steven F., Olefeldt, David, Paré, David, Parisien, Marc-André, Payette, Serge, Peng, Changhui, Pokrovsky, Oleg S., Rastetter, Edward B., Raymond, Peter A., Raynolds, Martha K., Rein, Guillermo, Reynolds, James F., Robards, Martin, Rogers, Brendan M., Schädel, Christina, Schaefer, Kevin, Schmidt, Inger K., Shvidenko, Anatoly, Sky, Jasper, Spencer, Robert G. M., Starr, Gregory, Striegl, Robert G., Teisserenc, Roman, Tranvik, Lars J., Virtanen, Tarmo, Welker, Jeffrey M., Zimov, Sergei
- Date Issued
- 2016-03-07
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000121
- Format
- Citation
- Title
- Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire: an expert assessment.
- Creator
- Abbott, Benjamin W, Jones, Jeremy B, Schuur, Edward A G, Chapin III, F Stuart, Bowden, William B, Bret-Harte, M Syndonia, Epstein, Howard E, Flannigan, Michael D, Harms, Tamara K, Hollingsworth, Teresa N, Mack, Michelle C, McGuire, A David, Natali, Susan M, Rocha, Adrian V, Tank, Suzanne E, Turetsky, Merritt R, Vonk, Jorien E, Wickland, Kimberly P, Aiken, George R, Alexander, Heather D, Amon, Rainer M W, Benscoter, Brian W, Bergeron, Yves, Bishop, Kevin, Blarquez, Olivier, Ben Bond-Lamberty, Breen, Amy L, Buffam, Ishi, Cai, Yihua, Carcaillet, Christopher, Carey, Sean K, Chen, Jing M, Chen, Han Y H, Christensen, Torben R, Cooper, Lee W, Cornelissen, J Hans C, de Groot, William J, DeLuca, Thomas H, Dorrepaal, Ellen, Fetcher, Ned, Finlay, Jacques C, Forbes, Bruce C, French, Nancy H F, Gauthier, Sylvie, Girardin, Martin P, Goetz, Scott J, Goldammer, Johann G, Gough, Laura, Grogan, Paul, Guo, Laodong, Higuera, Philip E, Hinzman, Larry, Hu, Feng Sheng, Hugelius, Gustaf, Jafarov, Elchin E, Jandt, Randi, Johnstone, Jill F, Jan Karlsson, Kasischke, Eric S, Kattner, Gerhard, Kelly, Ryan, Keuper, Frida, Kling, George W, Kortelainen, Pirkko, Kouki, Jari, Kuhry, Peter, Laudon, Hjalmar, Laurion, Isabelle, Macdonald, Robie W, Mann, Paul J, Martikainen, Pertti J, McClelland, James W, Molau, Ulf, Oberbauer, Steven F, Olefeldt, David, Paré, David, Parisien, Marc-André, Payette, Serge, Peng, Changhui, Pokrovsky, Oleg S, Rastetter, Edward B, Raymond, Peter A, Raynolds, Martha K, Rein, Guillermo, Reynolds, James F, Robards, Martin, Rogers, Brendan M, Schädel, Christina, Schaefer, Kevin, Schmidt, Inger K, Shvidenko, Anatoly, Sky, Jasper, Spencer, Robert G M, Starr, Gregory, Striegl, Robert G, Teisserenc, Roman, Tranvik, Lars J, Virtanen, Tarmo, Welker, Jeffrey M, Zimov, Sergei
- Date Issued
- 2016-03-07
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1088_1748-9326_11_3_034014_1632246943
- Format
- Citation
- Title
- Biophysically based computational models of astrocyte ~ neuron coupling and their functional significance.
- Creator
- Wade, John J., McDaid, Liam J., Harkin, Jim, Crunelli, Vincenzo, Kelso, J. A. Scott
- Date Issued
- 2013
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000028
- Format
- Citation
- Title
- Biotic Control of Surface pH and Evidence of Light-Induced H+ Pumping and Ca2+-H+ Exchange in a Tropical Crustose Coralline Alga.
- Creator
- Hofmann, Laurie C., Koch, Marguerite, de Beer, Dirk, Chin, Wei-Chun
- Abstract/Description
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Presently, an incomplete mechanistic understanding of tropical reef macroalgae photosynthesis and calcification restricts predictions of how these important autotrophs will respond to global change. Therefore, we investigated the mechanistic link between inorganic carbon uptake pathways, photosynthesis and calcification in a tropical crustose coralline alga (CCA) using microsensors. We measured pH, oxygen (O2), and calcium (Ca^2+) dynamics and fluxes at the thallus surface under ambient (8.1)...
Show morePresently, an incomplete mechanistic understanding of tropical reef macroalgae photosynthesis and calcification restricts predictions of how these important autotrophs will respond to global change. Therefore, we investigated the mechanistic link between inorganic carbon uptake pathways, photosynthesis and calcification in a tropical crustose coralline alga (CCA) using microsensors. We measured pH, oxygen (O2), and calcium (Ca^2+) dynamics and fluxes at the thallus surface under ambient (8.1) and low (7.8) seawater pH (pHSW) and across a range of irradiances. Acetazolamide (AZ) was used to inhibit extracellular carbonic anhydrase (CAext), which mediates hydrolysis of HCO3-, and 4,40 diisothiocyanatostilbene- 2,2'-disulphonate (DIDS) that blocks direct HCO3- uptake by anion exchange transport. Both inhibited photosynthesis, suggesting both diffusive uptake of CO2 via HCO3- hydrolysis to CO2 and direct HCO3- ion transport are important in this CCA. Surface pH was raised approximately 0.3 units at saturating irradiance, but less when CAext was inhibited. Surface pH was lower at pHSW 7.8 than pHSW 8.1 in the dark, but not in the light. The Ca^2+ fluxes were large, complex and temporally variable, but revealed net Ca2+ uptake under all conditions. The temporal variability in Ca^2+ dynamics was potentially related to localized dissolution during epithallial cell sloughing, a strategy of CCA to remove epiphytes. Simultaneous Ca^2+ and pH dynamics suggest the presence of Ca^2+/H^+ exchange. Rapid light-induced H^+ surface dynamics that continued after inhibition of photosynthesis revealed the presence of a light-mediated, but photosynthesis-independent, proton pump. Thus, the study indicates metabolic control of surface pH can occur in CCA through photosynthesis and light-inducible H^+ pumps. Our results suggest that complex light-induced ion pumps play an important role in biological processes related to inorganic carbon uptake and calcification in CCA.
Show less - Date Issued
- 2016-07-26
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000029
- Format
- Citation
- Title
- Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies.
- Creator
- García Rodríguez, Luis A., Martín-Pérez, Mar, Hennekens, Charles H., Rothwell, Peter M., Lanas, Angel, Eckle, Tobias
- Date Issued
- 2016-08-04
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000101
- Format
- Citation
- Title
- Boom and bust of the tawny Crazy Ant, Nylanderia fulva (Hymenoptera: Formicidae), on St. Croix, US Virgin Islands.
- Creator
- Wetterer, James K., Davis, Olasee, Williamson, Joe R.
- Date Issued
- 2014-09
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000208
- Format
- Citation