The development of complex neural networks relies on a careful balance of environmental cues to guide and shape both ends of the eventual connection. However, the correct wiring of circuits whose components share molecular profiles depends on a more elaborate phenomenon, competition. Despite being highly studied, there is still a lack of understanding as to the mechanism that allows molecularly identical cells to form exclusive connections with their targets. To address this complex question, we turned to a simple circuit within the genetically tractable fly. Responsible for the escape reflex, the Giant Fiber System is comprised of bilaterally symmetrical axons that innervate the ipsilateral "jump" motorneuron, TTMn in a 1:1 ratio. However, if a TTMn is unilaterally ablated prior to circuit formation, this ratio is disrupted and the deprived axon forms its presynaptic terminal on the opposite side. Midline crossing by the deprived axon led to exploration of a known pathway in giant fiber development, midline repulsion via Slit and Roundabout. Axons in which Roundabout levels were reduced through a natural pathway antagonist, Commissurelesss, crossed the midline freely, confirming a native, if normally restricted ability to do so. However, unlike the overlapping giant fiber terminals seen following ablation, these axons retained their wild exclusivity, elaborating their terminals toward a single TTMn. This supported our initial aim of uncovering a competitive force in giant fiber target selection. In addition to repulsion, I also examined the attractive pathway of Netrin and Frazzled for a possible role in target identification. Varying the levels of Frazzled receptors led to increased midline crossing and overlapped terminals, suggesting a connection between this attractive receptor and the repulsion pathway first examined. Frazzled has been shown to induce commissureless expression independent of its ligand, making it an important linchpin in the regulation of giant fiber guidance and competition. In fact, when allowed to traverse the midline, giant fibers responded to a Netrin increase with overlapping synaptic terminals. In this dissertation, I present a model in which giant fibers possess competitive machinery, driven by Netrin and triggered by Frazzled, underneath the naturally restrictive midline repulsion.

Globular clusters are found in the halos of all types of galaxies, and have been shown to play major roles in the formation of stars and galaxies. The purpose of this thesis is to advance our level of understanding of the dynamical evolution of globular clusters through N-body simulations of clusters with a range of circular, eccentric, and inclined orbits. Theoretical studies have historically assumed that globular clusters experience a static tidal field, however the orbits of globular clusters are all non-circular and the tidal field of most galaxies is not symmetric. Understanding how clusters evolve in realistic potentials allows for them to be used to constrain the formation, merger history, and evolution of a host galaxy and even map out the current size, shape, and strength of a galaxy's gravitational field. We find that dense and compact clusters evolve as if they are in isolation, despite being subject to a non-static tidal field. For larger clusters, tidal shocks and heating inject energy into the cluster and significantly alter its evolution compared to previous studies. We describe how a non-static field alters the mass loss rate and relaxation time of a cluster, and propose methods for calculating a cluster's size and orbit. We then apply our work to clusters in the giant galaxies M87, NGC 1399, and NGC 5128. We consider each cluster population to be a collection of metal poor and metal rich clusters and generate models with a range of orbital distributions. From our models we constrain the orbital anisotropy profile of each galaxy, place constraints on their formation and merger histories, and explore the effects of nearby galaxies on cluster evolution. By advancing studies of globular cluster evolution to include the effects of a non-static tidal field, we have made an important step towards accurately modelling globular clusters from birth to dissolution. Our work opens the door for globular clusters to be used as tools to study galaxy formation, evolution, and structure. Future studies will explore how galaxy formation and growth via the hierarchical merger of smaller galaxies will affect cluster evolution. / Thesis / Doctor of Philosophy (PhD)

Of all the Q-switching methods employed to operate a laser in giant pulse mode one of the simplest and most regularly used methods involves a rotating Porro prism. In this Thesis, experimental results are reported which show good agreement with predictions based on a rate equation model. The results indicate that it is possible to design a rotating prism Q-switched laser on the basis of those rate equations, and that the design when realized, should perform close to expectations. / Thesis / Doctor of Philosophy (PhD)

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13569号 / 論医博第2295号 / 新制||医||1068(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 濵﨑 洋子, 教授 生田 宏一, 教授 滝田 順子 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Viruses hold our attention for the horrific impact they have on human health and welfare. However, viruses are a critical part of our ecosystem and facilitate the cycling of carbon and other important nutrients. The cycle of virus infection, followed by host resistance and the subsequent evolution of new strains enables adaptation to changing hosts and the environment. Giant viruses, some with particle sizes large enough to be visible in light microscopes and their bewildering array of accessory genes, have captivated scientists and the general public since their discovery two decades ago. Giant viruses are part of the Nucleocytoviricota (NCV) whose members include both harmful agents (such as the causative agents of smallpox and swine hemorrhagic fever) and beneficial ones (such as those that provide biocontrol of insects, mitigation of toxic algal blooms and enzymes for biotechnology). Most of the giant viruses discovered, to date, are from marine and freshwater ecosystems where their hosts are abundant. In terrestrial soils, very few giant viruses have been revealed because of challenges in shifting through the astounding microbial genetic diversity in soil to assemble genomes from metagenomic data. Currently there is a lack of knowledge about abundance and genetic diversity of giant viruses in terrestrial soils, knowledge about their hosts and their influence on biogeochemical cycling. In 2018, giant viruses were discovered in the Barre Woods experimental warming plots at Harvard Forest. (Schulz et al 2018 Nature Communications). A novel environmental genomics approach involving filtration and fluorescence activating cell-sorting (FACS) was used to discover 16 Nucleocytoviricota (NCVs) in just a few grams of Harvard Forest soil. All these newly discovered viruses represent distinct lineages (new species, genera, and families). This experiment involved just two soil cores (1 warming and 1 control) and a single time point at Harvard Forest. There is much to learn about the terrestrial giant virus genetic biodiversity as these same viruses have not yet been discovered at other sites around the world. My research will focus on a genus of giant viruses with only three known representatives, all from Harvard Forest. They are Hyperionvirus (with the world’s 2nd largest virus genome at 2.4 MBp), Terrestrivrus the 10 th largest genome at 1.8 MBp), and Harvfovirus (the 15 th largest genome at 1.6 MBp). In the experimental warming plots the relative amount of bacteria to fungi has increased. We hypothesize that the relative increase in bacteria has led to an increase in protists, which feed on the bacteria, which in turn has led to an increase in giant viruses, which infect the protists. Because of the high genetic diversity in viruses and the lack of ribosomal genes, it is not possible to create primers that span the entire Nucleocytoviricota phylum or even at the family level. To test our hypothesis, we designed degenerate PCR primers that detect and quantify members of the genus containing the 3 giant Harvard Forest viruses. DNA was extracted from soil samples the soil (stored at -80C) from the 2017 temperature toggle experiment at Barre Woods in which the power to the warmed plots was turned off from late May until early September were used. The giant viruses were originally discovered in the sample just prior to turning off the power. We used 4 time points spanning the experiment with 8 samples from each the warmed and control plots (4 x 16 = 16 samples total). The primers were designed based on five hallmark genes that are present in most members of the Nucleocytoviricota. After amplification, the amount of DNA would be quantified and normalized. We expect to better understand the genetic diversity of this genus of giant viruses in the soil including the possibility of detecting new species in this genus.

Native American societies in the Yazoo Basin during the Mississippian Period (ca. 1000 – 1700 A.D.) extensively built platform mounds often associated with “elite” or “sacred” areas, and exotic or energy expensive artifacts. Excessive energy expenditure, or “waste” behaviors, may be explained with costly signaling and bet-hedging, hypotheses stemming from evolutionary theory. I argue that costly signaling may best explain the waste evident in hierarchical and agricultural Mississippian Period societies of the Mississippi Valley. Consequently, I feel that differing levels of energy expenditure may be evident from the remains of perishable construction excavated from mound summits and off-mound contexts. During that time, wattle and daub was a common method of wall construction in the Yazoo Basin, leaving abundant evidence at Mississippian sites. By studying imprints from preserved daub fragments, the use of specific construction methods can be compared between mound and non-mound contexts and relative energy expenditure assessed.

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