Formalizing affordances in situation

The representation of a perceptual scene by a computer is usually limited to numbers representing dimensions and colours. The theory of affordances attempted to provide a new way of representing an environment, with respect to a particular agent. The view was introduced as part of an entire field of psychology labeled as 'ecological,' which has since branched into computer science through the field of robotics, and formal methods. This thesis will describe the concept of affordances, review several existing formalizations, and take a brief look at applications to robotics. The formalizations put forth in the last 20 years have no agreed upon structure, only that both the agent and the environment must be taken in relation to one another. Situation theory has also been evolving since its inception in 1983 by Barwise & Perry. The theory provided a formal way to represent any arbitrary piece of information in terms of relations. This thesis will take a toy version of situation theory published in CSLI lecture notes no. 22, and add to the given ontologies. This thesis extends the given ontologies to include specialized affordance types, and individual object types. This allows for the definition of semantic objects called environments, which support a situation and a set of affordances, and niches which refer to a set of actions for an individual. Finally, a possible way for an environment to change into a new environment is suggested via the activation of an affordance

Precision mouse models with expanded tropism for human pathogens

A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics

Therapeutic targeting of cathepsin C::from pathophysiology to treatment

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials