Browsing by Subject "mathematical modeling"

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    Complex signal regulation drives the Arabidopsis immune network’s response to bacterial flagellin stimulus
    (2016-04) Hillmer, Rachel
    Systems biology is the study of how biological systems operate as a whole. Systems become complex when interactions between system parts dominate system behavior. To uncover the mechanisms by which complex biological systems operate, those interactions must be discovered and quantified. Further, to understand dynamic system behavior, mechanistic rules for how system parts are stimulated and regulate each other must be discovered. The plant immune signaling network, which protects plants from pathogens, is an especially complex system. Pathogens disable plant immune signaling with effectors; thus plant immunity must be robust against pathogen perturbation. Thus, deciphering the mechanisms that underlie the plant immune signaling network is met by a challenge: effects of single-gene mutations, on which traditional genetic analysis depends, are also buffered by the network. In this dissertation, a network reconstitution approach was taken, where the network is disassembled and then stepwise re-assembled, to accurately assign network functions to system parts, including interactions between parts. We define the plant immune signaling network in terms of 4 major signaling sectors controlled by the plant hormones jasmonate (JA), ethylene (ET), and salicylate (SA) sectors, and the major immune regulator phytoalexin-deficient 4 (PAD4). Dynamic transcriptome and hormone profiles after plant immune stimulus with bacterial flagellin were collected across a combinatorially complete set of mutants, lacking all combinations of these four sectors. These mutant profiles were used in (1) attempts to find mechanistic mathematical models of immune network behavior and to (2) characterize the four-sector network’s control of the flg22-responsive transcriptome. The work in this dissertation produced two main discoveries. First, that delay differential equations (DDEs) can be found which provide mechanistic explanations of immune network function; additional time course detail will be needed to confirm the accuracy of these models. Second, network buffering is extensive in the flg22-responsive transcriptome. As a result of this network buffering, our network reconstitution based interpretations of gene regulation are at points quite different from the regulatory mechanisms described in the plant immunity literature.
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    Estimating the contribution of N. gonorrhoeae infection to pelvic inflammatory disease and tubal factor infertility in the United States and the Infertility Belt of Africa
    (2022-04) Faherty, Emily
    Gonorrhea is the second most common bacterial sexually transmitted infection (STI) globally. Persistent gonorrhea infection can cause pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI). Infertility disproportionately impacts women in high fertility countries, especially in the Infertility Belt of Africa from Gabon to Tanzania. To examine gonorrhea’s contribution to these reproductive tract outcomes, we 1) conducted a survey and medical record review at Dodoma Christian Medical Center (DCMC) in Dodoma, Tanzania, 2) analyzed U.S. administrative claims data, and 3) created a mathematical model of STI transmission and reproductive tract disease among U.S. women.First, we examined determinants of female infertility by interviewing and reviewing medical records of 168 women seeking infertility treatment at DCMC. Women with PID had 1.9 (95% CI: 1.3-2.9) times the prevalence of TFI compared to women with other infertility factors. Logistic barriers to treatment were most common, regardless of women’s geographic residence. Next, we analyzed the rates of PID, EP, and TFI after gonorrhea diagnosis using the IBM MarketScan national claims database from 2013-2018 and tested an interaction in rates over time. We found elevated rates of PID, EP and TFI among women with a prior gonorrhea diagnosis compared to women who had no prior gonorrhea diagnoses. These rate ratios were steady over time, indicating that higher reported STI rates reflect increased infection burden, not greater incidence resulting from increased testing. Finally, we created a mathematical model simulating the disease process to estimate the number of cases of PID and TFI due to gonorrhea or chlamydia. We estimated that 24% of PID episodes and 26% of undetected tubal damage occurred among women who were previously infected with gonorrhea. Findings from this dissertation are timely due to increasing rates of gonorrhea infection and may motivate and inform global STI prevention efforts.
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    Understanding growth rate limitations in production of single-crystal cadmium zinc telluride (CZT) by the traveling heater method (THM)
    (2017-03) Peterson, Jeffrey
    Cadmium telluride (CdTe) and cadmium zinc telluride (CZT) are important optoelectronic materials with applications ranging from medical imaging to nuclear materials monitoring. However, CZT and CdTe have long been plagued by second-phase particles, inhomogeneity, and other defects. The traveling heater method (THM) is a promising approach for growing CZT and other compound semiconductors that has been shown to grow detector-grade crystals. In contrast to traditional directional solidification, the THM consists of a moving melt zone that simultaneously dissolves a polycrystalline feed while producing a single-crystal of material. Additionally, the melt is highly enriched in tellurium, which allows for growth at lower temperatures, limiting the presence of precipitated tellurium second-phase particles in the final crystal. Unfortunately, the THM growth of CZT is limited to millimeters per day when other growth techniques can grow an order of magnitude faster. To understand these growth limits, we employ a mathematical model of the THM system that is formulated to realistically represent the interactions of heat and species transport, fluid flow, and interfacial dissolution and growth under conditions of local thermodynamic equilibrium and steady-state growth. We examine the complicated interactions among zone geometry, continuum transport, phase change, and fluid flow driven by buoyancy. Of particular interest and importance is the formation of flow structures in the liquid zone of the THM that arise from the same physical mechanism as lee waves in atmospheric flows and demonstrate the same characteristic Brunt--V ais al a scaling. We show that flow stagnation and reversal associated with lee-wave formation are responsible for the accumulation of tellurium and supercooled liquid near the growth interface, even when the lee-wave vortex is not readily apparent in the overall flow structure. The supercooled fluid is posited to result in morphological instability at growth rates far below the limit predicted by the classical criterion by Tiller et al. for constitutional supercooling.