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• 1211. [Article] Policy Analysis of the Stage 2 Drinking Water Disinfenctants and Disinfection Byproducts Rule in the State of Oregon

  Examining committee chair: Professor Renee Irvin, PHD.

  Citation × Citation Citation Abstract Copy Title: Policy Analysis of the Stage 2 Drinking Water Disinfenctants and Disinfection Byproducts Rule in the State of Oregon Author: Duncan, Kari Jean, 1977- Year: 2005 Examining committee chair: Professor Renee Irvin, PHD. Title: Policy Analysis of the Stage 2 Drinking Water Disinfenctants and Disinfection Byproducts Rule in the State of Oregon Author: Duncan, Kari Jean, 1977- Year: 2005 Examining committee chair: Professor Renee Irvin, PHD. Close

• 1212. [Article] Myrtle Creek : Comprehensive plan

  154 pp. Item consists of two files: the comprehensive plan, and the plan map. Originally adopted October 17, 1978; latest amendments September 17, 1991. Captured September 16, 2005.

  Citation × Citation Citation Abstract Copy Title: Myrtle Creek : Comprehensive plan Author: Myrtle Creek (Or.), Douglas County (Or.) Year: 2005, 1991 154 pp. Item consists of two files: the comprehensive plan, and the plan map. Originally adopted October 17, 1978; latest amendments September 17, 1991. Captured September 16, 2005. Title: Myrtle Creek : Comprehensive plan Author: Myrtle Creek (Or.), Douglas County (Or.) Year: 2005, 1991 154 pp. Item consists of two files: the comprehensive plan, and the plan map. Originally adopted October 17, 1978; latest amendments September 17, 1991. Captured September 16, 2005. Close

• 1213. [Article] EPA policy on flexible state enforcement responses to small community violations: an assessment of activities and results, 1995-1998

  28 p.

  Citation × Citation Citation Abstract Copy Title: EPA policy on flexible state enforcement responses to small community violations: an assessment of activities and results, 1995-1998 Author: Dowling-Wu, Lynda Year: 2006, 1998 28 p. Title: EPA policy on flexible state enforcement responses to small community violations: an assessment of activities and results, 1995-1998 Author: Dowling-Wu, Lynda Year: 2006, 1998 28 p. Close

• 1214. [Article] Tualatin Notice of Adopted Amendment (2006-06-30)

  45 pp. Adopted 2006-06-30. Department of Land Conservation and Development Notice of Adopted Amendment

  Citation × Citation Citation Abstract Copy Title: Tualatin Notice of Adopted Amendment (2006-06-30) Author: Tualatin Year: 2014, 2006 45 pp. Adopted 2006-06-30. Department of Land Conservation and Development Notice of Adopted Amendment Title: Tualatin Notice of Adopted Amendment (2006-06-30) Author: Tualatin Year: 2014, 2006 45 pp. Adopted 2006-06-30. Department of Land Conservation and Development Notice of Adopted Amendment Close

• 1215. [Article] The perception and management of therapeutic risk

  55 pages

  Citation × Citation Citation Abstract Copy Title: The perception and management of therapeutic risk Author: Slovic, Paul Year: 2017, 1989 55 pages Title: The perception and management of therapeutic risk Author: Slovic, Paul Year: 2017, 1989 55 pages Close

• 1216. [Article] Adaptive Reuse: Explaining Collaborations within a Complex Process

  Examining committee: Gerardo Sandoval, chair, Kingston Heath

  Citation × Citation Citation Abstract Copy Title: Adaptive Reuse: Explaining Collaborations within a Complex Process Author: Bond, Christina Year: 2011 Examining committee: Gerardo Sandoval, chair, Kingston Heath Title: Adaptive Reuse: Explaining Collaborations within a Complex Process Author: Bond, Christina Year: 2011 Examining committee: Gerardo Sandoval, chair, Kingston Heath Close

• 1217. [Article] Health Insurance Exchanges

  Examining committee: Colleen Chrisinger

  Citation × Citation Citation Abstract Copy Title: Health Insurance Exchanges Author: Fracchia, Elena, Hall, Tiffany, Remer, Matthew, Saxe, Karen, Wu, Wei-Ting Year: 2011 Examining committee: Colleen Chrisinger Title: Health Insurance Exchanges Author: Fracchia, Elena, Hall, Tiffany, Remer, Matthew, Saxe, Karen, Wu, Wei-Ting Year: 2011 Examining committee: Colleen Chrisinger Close

• 1218. [Article] CONTEMPORARY GENETIC TOOLS FOR IN VIVO INVESTIGATIONS OF H3K27 DEMETHYLASES IN ZEBRAFISH CARDIOGENESIS

  Dynamic histone modification has emerged as a robust and versatile regulator of gene expression in eukaryotic cells. One such modification, the trimethylation of lysine 27 on histone H3 (H3K27me3) is facilitated ...

  Citation × Citation Citation Abstract Copy Title: CONTEMPORARY GENETIC TOOLS FOR IN VIVO INVESTIGATIONS OF H3K27 DEMETHYLASES IN ZEBRAFISH CARDIOGENESIS Author: Akerberg, Alexander Year: 2016 Dynamic histone modification has emerged as a robust and versatile regulator of gene expression in eukaryotic cells. One such modification, the trimethylation of lysine 27 on histone H3 (H3K27me3) is facilitated by the Polycomb repressive complex 2 (PRC2) and contributes to the localized repression of transcription. Subsequently, lysine specific demethylase Kdm6b (Jmjd3) can relieve the repressive H3K27me3 mark, allowing for transcriptional activation. In vitro studies have suggested a role for Kdm6b during mesodermal and cardiovascular differentiation in mammalian embryonic stem cells; however, this relationship has yet to be characterized in vivo. I utilized the advantages of the zebrafish model to investigate the in vivo roles of Kdm6b-family demethylases during development using a reverse genetic approach. I carried out two independent loss-of-function studies to analyze the role of Kdm6b-family demethylases during embryonic development in zebrafish. By comparing genetic loss-of-function and morpholino-mediated knockdown approaches, I found that morpholino–mediated knockdown of kdm6bb transcript produces off-target effects and does not portray an accurate representation of in vivo function. I then show that, while not required for early cardiogenesis, histone demethylases kdm6ba and kdm6bb function redundantly to promote late stage proliferation during heart ventricle trabeculation. These data reveal a previously unknown functional relationship and support the hypothesis that Kdm6b-family demethylases function primarily during later stages of development. Additionally, my description of morpholino-induced off-target effects supports the need to use extreme caution when interpreting morphant phenotypes. Due to the embryonic lethality exhibited by kdm6b-deficient embryos and the limited tools available for spatiotemporal transgene control in zebrafish, I was unable to investigate demethylase function within adult animals. I attempted to circumvent these limitations by creating an inducible gene expression system that uses tissue-specific transgenes that express the Gal4 transcription factor fused to the estrogen-binding domain of the human estrogen receptor. I showed that these Gal4-ERT driver lines confer rapid, tissue-specific induction of UAS-controlled transgenes following tamoxifen exposure in both embryos and adult fish. I then demonstrated how this technology could be used to define developmental windows of gene function by spatiotemporally controlling expression of constitutively active Notch1 in embryos. This dissertation contains previously published co-authored material. Title: CONTEMPORARY GENETIC TOOLS FOR IN VIVO INVESTIGATIONS OF H3K27 DEMETHYLASES IN ZEBRAFISH CARDIOGENESIS Author: Akerberg, Alexander Year: 2016 Dynamic histone modification has emerged as a robust and versatile regulator of gene expression in eukaryotic cells. One such modification, the trimethylation of lysine 27 on histone H3 (H3K27me3) is facilitated by the Polycomb repressive complex 2 (PRC2) and contributes to the localized repression of transcription. Subsequently, lysine specific demethylase Kdm6b (Jmjd3) can relieve the repressive H3K27me3 mark, allowing for transcriptional activation. In vitro studies have suggested a role for Kdm6b during mesodermal and cardiovascular differentiation in mammalian embryonic stem cells; however, this relationship has yet to be characterized in vivo. I utilized the advantages of the zebrafish model to investigate the in vivo roles of Kdm6b-family demethylases during development using a reverse genetic approach. I carried out two independent loss-of-function studies to analyze the role of Kdm6b-family demethylases during embryonic development in zebrafish. By comparing genetic loss-of-function and morpholino-mediated knockdown approaches, I found that morpholino–mediated knockdown of kdm6bb transcript produces off-target effects and does not portray an accurate representation of in vivo function. I then show that, while not required for early cardiogenesis, histone demethylases kdm6ba and kdm6bb function redundantly to promote late stage proliferation during heart ventricle trabeculation. These data reveal a previously unknown functional relationship and support the hypothesis that Kdm6b-family demethylases function primarily during later stages of development. Additionally, my description of morpholino-induced off-target effects supports the need to use extreme caution when interpreting morphant phenotypes. Due to the embryonic lethality exhibited by kdm6b-deficient embryos and the limited tools available for spatiotemporal transgene control in zebrafish, I was unable to investigate demethylase function within adult animals. I attempted to circumvent these limitations by creating an inducible gene expression system that uses tissue-specific transgenes that express the Gal4 transcription factor fused to the estrogen-binding domain of the human estrogen receptor. I showed that these Gal4-ERT driver lines confer rapid, tissue-specific induction of UAS-controlled transgenes following tamoxifen exposure in both embryos and adult fish. I then demonstrated how this technology could be used to define developmental windows of gene function by spatiotemporally controlling expression of constitutively active Notch1 in embryos. This dissertation contains previously published co-authored material. Close

• 1219. [Article] Investigating Developmental Cues in Valvulogenesis

  Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated, and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed ...

  Citation × Citation Citation Abstract Copy Title: Investigating Developmental Cues in Valvulogenesis Author: Bosada, Fernanda Year: 2016 Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated, and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed to contribute to endocardial-to-mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/β-catenin signaling by chemically-inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Further, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/β-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/β-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects. This work suggests that Wnt/β-catenin maintains a subpopulation of valve mesenchyme in a less-differentiated, progenitor-like state that allows these cells to respond to mitogens and morphogens. The coordinated interplay of signals with distinct effects on a “progenitor cell” pool is a common logic mechanism for balanced tissue growth and differentiation in many biological contexts. Inspired by epithelial organ homeostasis processes, we identified specific and dynamic expression of the well-established quiescent stem cell marker Lrig1 in the developing valves. Endocardial Lrig1 likely moderates ErbB2 levels and thereby signaling output to prevent excessive EMT and resulting pathologically enlarged valves. Finally, we use Cre-mediated lineage labeling to show that the cusps of the semilunar valves have differential mesenchymal origins and that the localization of said distinct mesenchyme may account for the discretely patterned extracellular matrix of mature valves. This dissertation includes previously published and unpublished coauthored material. Title: Investigating Developmental Cues in Valvulogenesis Author: Bosada, Fernanda Year: 2016 Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated, and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed to contribute to endocardial-to-mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/β-catenin signaling by chemically-inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Further, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/β-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/β-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects. This work suggests that Wnt/β-catenin maintains a subpopulation of valve mesenchyme in a less-differentiated, progenitor-like state that allows these cells to respond to mitogens and morphogens. The coordinated interplay of signals with distinct effects on a “progenitor cell” pool is a common logic mechanism for balanced tissue growth and differentiation in many biological contexts. Inspired by epithelial organ homeostasis processes, we identified specific and dynamic expression of the well-established quiescent stem cell marker Lrig1 in the developing valves. Endocardial Lrig1 likely moderates ErbB2 levels and thereby signaling output to prevent excessive EMT and resulting pathologically enlarged valves. Finally, we use Cre-mediated lineage labeling to show that the cusps of the semilunar valves have differential mesenchymal origins and that the localization of said distinct mesenchyme may account for the discretely patterned extracellular matrix of mature valves. This dissertation includes previously published and unpublished coauthored material. Close

• 1220. [Article] Experimental Evolution of Phenotypic Plasticity for Stress Resistance in the Nematode Caenorhabditis remanei

  Many organisms can acclimate to new environments through phenotypic plasticity, a complex trait that can be heritable, be subject to selection, and evolve. However, the rate and genetic basis of plasticity ...

  Citation × Citation Citation Abstract Copy Title: Experimental Evolution of Phenotypic Plasticity for Stress Resistance in the Nematode Caenorhabditis remanei Author: Sikkink, Kristin Year: 2014 Many organisms can acclimate to new environments through phenotypic plasticity, a complex trait that can be heritable, be subject to selection, and evolve. However, the rate and genetic basis of plasticity evolution remain largely unknown. Experimentally evolved populations of the nematode Caenorhabditis remanei were created by selecting for stress resistance under different environmental conditions. This resource was used to address key questions about how phenotypic plasticity evolves and what the genetic basis of plasticity is. Here, I highlight ways in which a fuller understanding of the environmental context influences our interpretation of the evolution of phenotypic plasticity. In a population selected to withstand heat stress, an apparent case of genetic assimilation did not show correlated changes in global gene regulation. However, further investigation revealed that the induced plasticity was not fixed across environments, but rather the threshold for the response was shifted over evolutionary time. Similarly, the past environment experienced by populations can play a role in directing the multivariate response to selection. Correlated responses to selection between traits and across environments were examined. The pattern of covariation in the evolutionary response among traits differed depending on the environment in which selection occurred, indicating that there exists variation in pleiotropy across the stress response network that is highly sensitive to the external environment. To understand how the patterns of pleiotropy are altered by environment and evolution, there is a pressing need to determine the structure of the molecular networks underlying plastic phenotypes. Using RNA-sequencing, the structure of the gene regulatory network is examined for a subset of evolved populations from one environment. Key modules within this network were identified that are strong candidates for the evolution of phenotypic plasticity in this system. Together, the data presented in this dissertation provide a comprehensive view of the myriad ways in which the environment shapes the genetic architecture of stress response phenotypes and directs the evolution of phenotypic plasticity. Additionally, the structure of transcriptional network provides valuable insight into the genetic basis of adaptation to environmental change and the evolution of phenotypic plasticity. This dissertation includes both previously published and co-authored material. Title: Experimental Evolution of Phenotypic Plasticity for Stress Resistance in the Nematode Caenorhabditis remanei Author: Sikkink, Kristin Year: 2014 Many organisms can acclimate to new environments through phenotypic plasticity, a complex trait that can be heritable, be subject to selection, and evolve. However, the rate and genetic basis of plasticity evolution remain largely unknown. Experimentally evolved populations of the nematode Caenorhabditis remanei were created by selecting for stress resistance under different environmental conditions. This resource was used to address key questions about how phenotypic plasticity evolves and what the genetic basis of plasticity is. Here, I highlight ways in which a fuller understanding of the environmental context influences our interpretation of the evolution of phenotypic plasticity. In a population selected to withstand heat stress, an apparent case of genetic assimilation did not show correlated changes in global gene regulation. However, further investigation revealed that the induced plasticity was not fixed across environments, but rather the threshold for the response was shifted over evolutionary time. Similarly, the past environment experienced by populations can play a role in directing the multivariate response to selection. Correlated responses to selection between traits and across environments were examined. The pattern of covariation in the evolutionary response among traits differed depending on the environment in which selection occurred, indicating that there exists variation in pleiotropy across the stress response network that is highly sensitive to the external environment. To understand how the patterns of pleiotropy are altered by environment and evolution, there is a pressing need to determine the structure of the molecular networks underlying plastic phenotypes. Using RNA-sequencing, the structure of the gene regulatory network is examined for a subset of evolved populations from one environment. Key modules within this network were identified that are strong candidates for the evolution of phenotypic plasticity in this system. Together, the data presented in this dissertation provide a comprehensive view of the myriad ways in which the environment shapes the genetic architecture of stress response phenotypes and directs the evolution of phenotypic plasticity. Additionally, the structure of transcriptional network provides valuable insight into the genetic basis of adaptation to environmental change and the evolution of phenotypic plasticity. This dissertation includes both previously published and co-authored material. Close