E-NTPDases in human airways: Regulation and relevance for chronic lung diseases

Chronic obstructive lung diseases are characterized by the inability to prevent bacterial infection and a gradual loss of lung function caused by recurrent inflammatory responses. In the past decade, numerous studies have demonstrated the importance of nucleotide-mediated bacterial clearance. Their interaction with P2 receptors on airway epithelia provides a rapid ‘on-and-off’ signal stimulating mucus secretion, cilia beating activity and surface hydration. On the other hand, abnormally high ATP levels resulting from damaged epithelia and bacterial lysis may cause lung edema and exacerbate inflammatory responses. Airway ATP concentrations are regulated by ecto nucleoside triphosphate diphosphohydrolases (E-NTPDases) which are expressed on the mucosal surface and catalyze the sequential dephosphorylation of nucleoside triphosphates to nucleoside monophosphates (ATP → ADP → AMP). The common bacterial product, Pseudomonas aeruginosa lipopolysaccharide (LPS), induces an acute reduction in azide-sensitive E-NTPDase activities, followed by a sustained increase in activity as well as NTPDase 1 and NTPDase 3 expression. Accordingly, chronic lung diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia, are characterized by higher rates of nucleotide elimination, azide-sensitive E-NTPDase activities and expression. This review integrates the biphasic regulation of airway E-NTPDases with the function of purine signaling in lung diseases. During acute insults, a transient reduction in E-NTPDase activities may be beneficial to stimulate ATP-mediated bacterial clearance. In chronic lung diseases, elevating E-NTPDase activities may represent an attempt to prevent P2 receptor desensitization and nucleotide-mediated lung damage

Firm performance during a crisis : effects of adhocracy culture, incremental product innovation, and firm size

202208 bckwVersion of RecordOthersPenn State University Social Science Research InstituteEarly releas

An evaluation of integer programming models for restaurant reservations

A notable difference in rooms (hotel) revenue management reservations versus table (restaurant) revenue management (TRM) reservations is the variation that occurs in duration. In the hotel setting, durations are explicit in the reservation itself: a stay of a specified number of nights. In restaurants, by contrast, there is a natural variation in the amount of time parties are at the table. This duration variation presents interesting challenges to TRM. Dealing with these challenges is our goal in the article. Specifically, we introduce and evaluate 10 different models for restaurant capacity and reservations, five each of two different types. In one type of model, tables are pooled and parties are not explicitly matched to tables; in the other parties are matched to specific tables. The objective is to maximize revenue (or contribution) from known reservation demand. Variables are both the mix of tables in the restaurant and the reservations accepted. An important ancillary goal we have is to evaluate the effectiveness of the models from the perspective of customers, specifically examining whether a table is ready for them at the time of the reservation, an issue of high importance to restaurant patrons. Of the 10 models, seven define a pareto frontier between revenue and service; of those seven, five are pooling models. We use this frontier to offer advice to restaurateurs looking to better manage reservations.Thompson2_Evaluation_of_integer.pdf: 698 downloads, before Aug. 1, 2020