Swingbed Amine Carbon Dioxide Removal Flight Experiment - Feasibility Study and Concept Development for Cost-Effective Exploration Technology Maturation on The International Space Station

The completion of International Space Station Assembly and transition to a full six person crew has created the opportunity to create and implement flight experiments that will drive down the ultimate risks and cost for human space exploration by maturing exploration technologies in realistic space environments that are impossible or incredibly costly to duplicate in terrestrial laboratories. An early opportunity for such a technology maturation experiment was recognized in the amine swingbed technology baselined for carbon dioxide and humidity control on the Orion spacecraft and Constellation Spacesuit System. An experiment concept using an existing high fidelity laboratory swing bed prototype has been evaluated in a feasibility and concept definition study leading to the conclusion that the envisioned flight experiment can be both feasible and of significant value for NASA s space exploration technology development efforts. Based on the results of that study NASA has proceeded with detailed design and implementation for the flight experiment. The study effort included the evaluation of technology risks, the extent to which ISS provided unique opportunities to understand them, and the implications of the resulting targeted risks for the experiment design and operational parameters. Based on those objectives and characteristics, ISS safety and integration requirements were examined, experiment concepts developed to address them and their feasibility assessed. This paper will describe the analysis effort and conclusions and present the resulting flight experiment concept. The flight experiment, implemented by NASA and launched in two packages in January and August 2011, integrates the swing bed with supporting elements including electrical power and controls, sensors, cooling, heating, fans, air- and water-conserving functionality, and mechanical packaging structure. It is now on board the ISS awaiting installation and activation

Mathematical Model of Nucleotide Regulation on Airway Epithelia: IMPLICATIONS FOR AIRWAY HOMEOSTASIS

In the airways, adenine nucleotides support a complex signaling network mediating host defenses. Released by the epithelium into the airway surface liquid (ASL) layer, they regulate mucus clearance through P2 (ATP) receptors, and following surface metabolism through P1 (adenosine; Ado) receptors. The complexity of ASL nucleotide regulation provides an ideal subject for biochemical network modeling. A mathematical model was developed to integrate nucleotide release, the ectoenzymes supporting the dephosphorylation of ATP into Ado, Ado deamination into inosine (Ino), and nucleoside uptake. The model also includes ecto-adenylate kinase activity and feed-forward inhibition of Ado production by ATP and ADP. The parameters were optimized by fitting the model to experimental data for the steady-state and transient concentration profiles generated by adding ATP to polarized primary cultures of human bronchial epithelial (HBE) cells. The model captures major aspects of ATP and Ado regulation, including their >4-fold increase in concentration induced by mechanical stress mimicking normal breathing. The model also confirmed the independence of steady-state nucleotide concentrations on the ASL volume, an important regulator of airway clearance. An interactive approach between simulations and assays revealed that feed-forward inhibition is mediated by selective inhibition of ecto-5′-nucleotidase. Importantly, the model identifies ecto-adenylate kinase as a key regulator of ASL ATP and proposes novel strategies for the treatment of airway diseases characterized by impaired nucleotide-mediated clearance. These new insights into the biochemical processes supporting ASL nucleotide regulation illustrate the potential of this mathematical model for fundamental and clinical research

A mechanochemical model for auto-regulation of lung airway surface layer volume

We develop a proof-of-principle model for auto-regulation of water volume in the lung airway surface layer (ASL) by coupling biochemical kinetics, transient ASL volume, and homeostatic mechanical stresses. The model is based on the hypothesis that ASL volume is sensed through soluble mediators and phasic stresses generated by beating cilia and air drag forces. Model parameters are fit based on available data on human bronchial epithelial cell cultures. Simulations then demonstrate that homeostatic volume regulation is a natural consequence of the processes described. The model maintains ASL volume within a physiological range that modulates with phasic stress frequency and amplitude. Next, we show that the model successfully reproduces the responses of cell cultures to significant isotonic and hypotonic challenges, and to hypertonic saline, an effective therapy for mucus hydration in cystic fibrosis patients. These results compel an advanced airway hydration model with therapeutic value that will necessitate detailed kinetics of multiple molecular pathways, feedback to ASL viscoelasticity properties, and stress signaling from the ASL to the cilia and epithelial cells