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Rasmussen","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"ref42","doi-asserted-by":"crossref","first-page":"L92","DOI":"10.1152\/ajplung.90388.2008","article-title":"Tracheobronchial air-liquid interface cell culture: a model for innate mucosal defense of the upper airways?","volume":"296","author":"M. Kesimer","year":"2009","journal-title":"American Journal of Physiology-Lung Cellular and Molecular Physiology"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"e87681","DOI":"10.1371\/journal.pone.0087681","article-title":"A Biophysical Basis for Mucus Solids Concentration as a Candidate Biomarker for Airways Disease","volume":"9","author":"D.B. Hill","year":"2014","journal-title":"PloS one"},{"key":"ref44","unstructured":"Bird, R.B., R. Armstrong, and O. Hassager, Dynamics of polymeric liquids. 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