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- Genre: Masters Thesis
- Resource Type: Text
- Status: Published
Description
Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great efforts to get a properly attenuated Salmonella vaccine strain for a long time, but could not achieve a balance between attenuation and immunogenicity. So the regulated delayed attenuation/lysis Salmonella vaccine vectors were proposed as a design to seek this balance. The research work is progressing steadily, but more improvements need to be made. As one of the possible improvements, the cyclic adenosine monophosphate (cAMP) -independent cAMP receptor protein (Crp*) is expected to protect the Crp-dependent crucial regulator, araC PBAD, in these vaccine designs from interference by glucose, which decreases synthesis of cAMP, and enhance the colonizing ability by and immunogenicity of the vaccine strains. In this study, the cAMP-independent crp gene mutation, crp-70, with or without araC PBAD promoter cassette, was introduced into existing Salmonella vaccine strains. Then the plasmid stability, growth rate, resistance to catabolite repression, colonizing ability, immunogenicity and protection to challenge of these new strains were compared with wild-type crp or araC PBAD crp strains using western blots, enzyme-linked immunosorbent assays (ELISA) and animal studies, so as to evaluate the effects of the crp-70 mutation on the vaccine strains. The performances of the crp-70 strains in some aspects were closed to or even exceeded the crp+ strains, but generally they did not exhibit the expected advantages compared to their wild-type parents. Crp-70 rescued the expression of araC PBAD fur from catabolite repression. The strain harboring araC PBAD crp-70 was severely affected by its slow growth, and its colonizing ability and immunogenicity was much weaker than the other strains. The Pcrp crp-70 strain showed relatively good ability in colonization and immune stimulation. Both the araC PBAD crp-70 and the Pcrp crp-70 strains could provide certain levels of protection against the challenge with virulent pneumococci, which were a little lower than for the crp+ strains.
ContributorsShao, Shihuan (Author) / Curtiss, Roy (Thesis advisor) / Arizona State University (Publisher)
Created2012
Description
Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021
Description
Intervertebral Disc Degeneration (IVDD) is a complex phenomenon characterizing the desiccation and structural compromise of the primary joint in the human spine. The intervertebral disc (IVD) serves to connect vertebral bodies, cushion shock, and allow for flexion and extension of the vertebral column. Often presenting in the 4th or 5th decades of life as low back pain, this disease was originally believed to be the result of natural “wear and tear” coupled with repetitive mechanical insult, and as such most studies focus on patients between 40 and 50 years of age. Research over the past two decades, however, has demonstrated that environmental factors have only a modest effect on disc degeneration, with genetic influences playing a much more substantial role. Extensive research has focused on this process, though definitive risk factors and a clear pathophysiology have proven elusive. The aim of this study was to assemble a cohort of patients exhibiting definitive signs of degeneration who were well below the average age of presentation, with minimal or no exposure to suspected environmental risk factors and to conduct a targeted genome analysis in an attempt to elucidate a common genetic component. Through whole genome sequencing and analysis, the results corroborated findings in a previous study, as well as demonstrated a potential connection and influence between mutations found in IVD structural or functional genes, and the provocation of IVDD. Though the sample size was limited in scale and age, these findings suggest that further IVDD research into the association of variants in collagen, aggrecan and the insulin-like growth factor receptor genes of young patients with an early presentation of disc degeneration and minimal exposure to suspected risk factors is merited.
ContributorsFulton, Travis (Author) / Liebig, Juergen (Thesis advisor) / Neisewander, Janet (Committee member) / Theodore, Nicholas (Committee member) / Arizona State University (Publisher)
Created2016