We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.
We consider the effects of social learning on the individual learning and genetic evolution of a colony of artificial agents capable of genetic, individual and social modes of adaptation. We confirm that there is strong selection pressure to acquire traits of individual learning and social learning when these are adaptive traits. We show that selection pressure for learning of either kind can supress selection pressure for reproduction or greater fitness. We show that social learning differs from individual learning in that it can support a second evolutionary system that is decoupled from the biological evolutionary system. This decoupling leads to an emergent interaction where immature agents are more likely to engage in learning activities than mature agents.
We present a model for evolving agents using both genetic and cultural inheritance mechanisms. Within each agent our model maintains two distinct information stores we call the genome and the memome. Processes of adaptation are modeled as evolutionary processes at each level of adaptation (phylogenetic, ontogenetic, sociogenetic). We review relevant competing models and we show how our model improves on previous attempts to model genetic and cultural evolutionary processes. In particular we argue our model can achieve divergent gene-culture co-evolution.
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