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Hydrogen sulfide (H2S) is well known as a highly toxic environmental chemical threat. Prolonged exposure to H2S can lead to the formation of pulmonary edema. However, the mechanisms of how H2S facilitates edema formation are poorly understood. Since edema formation can be enhanced by an impaired clearance of electrolytes and, consequently, fluid across the alveolar epithelium, it was questioned whether H2S may interfere with transepithelial electrolyte absorption. Electrolyte absorption was electrophysiologically measured across native distal lung preparations (Xenopus laevis) in Ussing chambers. The exposure of lung epithelia to H2S decreased net transepithelial electrolyte absorption. This was due to an impairment of amiloride-sensitive sodium transport. H2S inhibited the activity of the Na+/K+-ATPase as well as lidocaine-sensitive potassium channels located in the basolateral membrane of the epithelium. Inhibition of these transport molecules diminishes the electrochemical gradient which is necessary for transepithelial sodium absorption. Since sodium absorption osmotically facilitates alveolar fluid clearance, interference of H2S with the epithelial transport machinery provides a mechanism which enhances edema formation in H2S-exposed lungs.
We explore the potential of stereoscopic 3D (S3D) vision in offering distinct gameplay using an S3D-specific game called Deepress3D. Our game utilizes established S3D design principles for optimizing GUI design, visual comfort and game mechanics which rely on depth perception in time-pressured spatial conflicts. The game collects detailed S3D player metrics and allows players to choose between different, evenly matched strategies. We conducted a between subjects study comparing S3D and monoscopic versions of Deepress3D that examined player behavior and performance and measured user-reported data on presence, simulator sickness, and game experience.
Gene expression and cell growth rely on the intracellular concentration of amino acids, which in metazoans depends on extracellular amino acid availability and transmembrane transport. To investigate the impact of extracellular amino acid concentrations on the expression of a concentrative amino acid transporter, we overexpressed the main kidney proximal tubule luminal neutral amino acid transporter B0AT1-collectrin (SLC6A19-TMEM27) in MDCK cell epithelia. Exogenously expressed proteins co-localized at the luminal membrane and mediated neutral amino acid uptake. However, the transgenes were lost over few cell culture passages. In contrast, the expression of a control transgene remained stable. To test whether this loss was due to inappropriately high amino acid uptake, freshly transduced MDCK cell lines were cultivated either with physiological amounts of amino acids or with the high concentration found in standard cell culture media. Expression of exogenous transporters was unaffected by physiological amino acid concentration in the media. Interestingly, mycoplasma infection resulted in a significant increase in transgene expression and correlated with the rapid metabolism of L-arginine. However, L-arginine metabolites were shown to play no role in transgene expression. In contrast, activation of the GCN2 pathway revealed by an increase in eIF2α phosphorylation may trigger transgene derepression. Taken together, high extracellular amino acid concentration provided by cell culture media appears to inhibit the constitutive expression of concentrative amino acid transporters whereas L-arginine depletion by mycoplasma induces the expression of transgenes possibly via stimulation of the GCN2 pathway.
This thesis presents an approach to automatically adjust the parameters of a Java application run on the IBM J9 Virtual Machine in order to improve its performance. It works by analyzing the logfile the VM generates and searching for specific behavioral patterns. These patterns are matched against a list of known patterns for which rules exist that specify how to adapt the VM to the given application. Adapting the application is done by adding parameters and changing existing ones, for example to achieve a better heap usage. The process is fully automated and carried out by a toolkit developed for this thesis. The toolkit iteratively cycles through multiple possible parameter sets, benchmarks them and proposes the best alternative to the user. The user can, without any prior knowledge about the Java application or the VM improve the performance of the deployed application.