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  • 1
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    Reconstituting organ-level lung functions on a chip (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-06-26
    Description: Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huh, Dongeun -- Matthews, Benjamin D -- Mammoto, Akiko -- Montoya-Zavala, Martin -- Hsin, Hong Yuan -- Ingber, Donald E -- R01-ES016665/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jun 25;328(5986):1662-8. doi: 10.1126/science.1188302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576885" target="_blank"〉PubMed〈/a〉
    Keywords: Air ; Animals ; *Biomimetic Materials ; Blood-Air Barrier ; Capillaries/*physiology ; Capillary Permeability ; Cells, Cultured ; Endothelial Cells/*physiology ; Escherichia coli/immunology ; Humans ; Immunity, Innate ; Inflammation ; Lung/blood supply/physiology ; Mice ; *Microfluidic Analytical Techniques ; Microtechnology ; Nanoparticles/toxicity ; Neutrophil Infiltration ; Oxidative Stress ; Pneumocytes/*physiology ; Pulmonary Alveoli/*blood supply/cytology/immunology/*physiology ; Respiration ; Silicon Dioxide/toxicity ; Stress, Mechanical
    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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    Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-07-07
    Description: Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korin, Netanel -- Kanapathipillai, Mathumai -- Matthews, Benjamin D -- Crescente, Marilena -- Brill, Alexander -- Mammoto, Tadanori -- Ghosh, Kaustabh -- Jurek, Samuel -- Bencherif, Sidi A -- Bhatta, Deen -- Coskun, Ahmet U -- Feldman, Charles L -- Wagner, Denisa D -- Ingber, Donald E -- New York, N.Y. -- Science. 2012 Aug 10;337(6095):738-42. doi: 10.1126/science.1217815. Epub 2012 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22767894" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomimetic Materials ; Blood Circulation ; Drug Delivery Systems/*methods ; Fibrinolytic Agents/*administration & dosage ; Hemodynamics ; Hemorheology ; Lactic Acid ; Male ; Mesenteric Arteries ; Mesenteric Vascular Occlusion/*drug therapy ; Mice ; Mice, Inbred C57BL ; Microfluidic Analytical Techniques ; Models, Anatomic ; *Nanoparticles ; Polyglycolic Acid ; Pulmonary Embolism/*drug therapy ; Stress, Mechanical ; Thrombosis/*drug therapy/prevention & control ; Tissue Plasminogen Activator/*administration & dosage
    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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    Analysis of four-dimensional variational state estimation of the Hawaiian waters (2012)
    Wiley
    Details
    Publication Date: 2012-03-09
    Description: In this study, we evaluate results from an incremental strong constraint four-dimensional variational data assimilation (IS4D-Var) experiment applied to the circulation around the Hawaiian Islands using the Regional Ocean Modeling System (ROMS). Assimilated observations include (1) satellite-derived high-resolution swath radiometer sea surface temperatures (SST) and along-track altimetric sea surface heights (SSH) and (2) in situ temperature and salinity profiles from Argo floats, autonomous Seagliders, and shipboard conductivity-temperature-depth. Two assimilation configurations are compared: adjusting initial conditions versus adjusting both initial conditions along with atmospheric forcing. In the latter case, we compare two separate forcing products. For all experiments, we investigate how the assimilation alters the tidal, inertial, and mesoscale variability. Significant improvements in the observation-model fit are found for SST and salinity regardless of assimilation configuration or atmospheric forcing; however, significant change to the subsurface temperature is made when adjusting only initial conditions. Baroclinic tides are altered during the assimilation because of changes in the density field in regions of strong internal tide generation. Spurious inertial oscillations are found in assimilation circulations that are associated with the IS4D-Var increment when using either SST or SSH observations; however, this increase in the inertial energy had minimal effect on the mesoscale variability.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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