Matching Items (87)
Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
Description
The border policies of the United States and Mexico that have evolved over the previous decades have pushed illegal immigration and drug smuggling to remote and often public lands. Valuable natural resources and tourist sites suffer an inordinate level of environmental impacts as a result of activities, from new roads and trash to cut fence lines and abandoned vehicles. Public land managers struggle to characterize impacts and plan for effective landscape level rehabilitation projects that are the most cost effective and environmentally beneficial for a region given resource limitations. A decision support tool is developed to facilitate public land management: Borderlands Environmental Rehabilitation Spatial Decision Support System (BERSDSS). The utility of the system is demonstrated using a case study of the Sonoran Desert National Monument, Arizona.
ContributorsFisher, Sharisse (Author) / Murray, Alan T. (Thesis advisor) / Wentz, Elizabeth (Committee member) / Rey, Sergio (Committee member) / Arizona State University (Publisher)
Created2013
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
There exist many facets of error and uncertainty in digital spatial information. As error or uncertainty will not likely ever be completely eliminated, a better understanding of its impacts is necessary. Spatial analytical approaches, in particular, must somehow address data quality issues. This can range from evaluating impacts of potential data uncertainty in planning processes that make use of methods to devising methods that explicitly account for error/uncertainty. To date, little has been done to structure methods accounting for error. This research focuses on developing methods to address geographic data uncertainty in spatial optimization. An integrated approach that characterizes uncertainty impacts by constructing and solving a new multi-objective model that explicitly incorporates facets of data uncertainty is developed. Empirical findings illustrate that the proposed approaches can be applied to evaluate the impacts of data uncertainty with statistical confidence, which moves beyond popular practices of simulating errors in data. Spatial uncertainty impacts are evaluated in two contexts: harvest scheduling and sex offender residency. Owing to the integration of spatial uncertainty, the detailed multi-objective models are more complex and computationally challenging to solve. As a result, a new multi-objective evolutionary algorithm is developed to address the computational challenges posed. The proposed algorithm incorporates problem-specific spatial knowledge to significantly enhance the capability of the evolutionary algorithm for solving the model.
ContributorsWei, Ran (Author) / Murray, Alan T. (Thesis advisor) / Anselin, Luc (Committee member) / Rey, Segio J (Committee member) / Mack, Elizabeth A. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Facility location models are usually employed to assist decision processes in urban and regional planning. The focus of this research is extensions of a classic location problem, the Weber problem, to address continuously distributed demand as well as multiple facilities. Addressing continuous demand and multi-facilities represents major challenges. Given advances in geographic information systems (GIS), computational science and associated technologies, spatial optimization provides a possibility for improved problem solution. Essential here is how to represent facilities and demand in geographic space. In one respect, spatial abstraction as discrete points is generally assumed as it simplifies model formulation and reduces computational complexity. However, errors in derived solutions are likely not negligible, especially when demand varies continuously across a region. In another respect, although mathematical functions describing continuous distributions can be employed, such theoretical surfaces are generally approximated in practice using finite spatial samples due to a lack of complete information. To this end, the dissertation first investigates the implications of continuous surface approximation and explicitly shows errors in solutions obtained from fitted demand surfaces through empirical applications. The dissertation then presents a method to improve spatial representation of continuous demand. This is based on infill asymptotic theory, which indicates that errors in fitted surfaces tend to zero as the number of sample points increases to infinity. The implication for facility location modeling is that a solution to the discrete problem with greater demand point density will approach the theoretical optimum for the continuous counterpart. Therefore, in this research discrete points are used to represent continuous demand to explore this theoretical convergence, which is less restrictive and less problem altering compared to existing alternatives. The proposed continuous representation method is further extended to develop heuristics to solve the continuous Weber and multi-Weber problems, where one or more facilities can be sited anywhere in continuous space to best serve continuously distributed demand. Two spatial optimization approaches are proposed for the two extensions of the Weber problem, respectively. The special characteristics of those approaches are that they integrate optimization techniques and GIS functionality. Empirical results highlight the advantages of the developed approaches and the importance of solution integration within GIS.
ContributorsYao, Jing (Author) / Murray, Alan T. (Thesis advisor) / Mirchandani, Pitu B. (Committee member) / Kuby, Michael J (Committee member) / Arizona State University (Publisher)
Created2012
Description
Decades ago in the U.S., clear lines delineated which neighborhoods were acceptable for certain people and which were not. Techniques such as steering and biased mortgage practices continue to perpetuate a segregated outcome for many residents. In contrast, ethnic enclaves and age restricted communities are viewed as voluntary segregation based on cultural and social amenities. This diversity surrounding the causes of segregation are not just region-wide characteristics, but can vary within a region. Local segregation analysis aims to uncover this local variation, and hence open the door to policy solutions not visible at the global scale. The centralization index, originally introduced as a global measure of segregation focused on spatial concentration of two population groups relative a region's urban center, has lost relevancy in recent decades as regions have become polycentric, and the index's magnitude is sensitive to the particular point chosen as the center. These attributes, which make it a poor global measure, are leveraged here to repurpose the index as a local measure. The index's ability to differentiate minority from majority segregation, and its focus on a particular location within a region make it an ideal local segregation index. Based on the local centralization index for two groups, a local multigroup variation is defined, and a local space-time redistribution index is presented capturing change in concentration of a single population group over two time periods. Permutation based inference approaches are used to test the statistical significance of measured index values. Applications to the Phoenix, Arizona metropolitan area show persistent cores of black and white segregation over the years 1990, 2000 and 2010, and a trend of white segregated neighborhoods increasing at a faster rate than black. An analysis of the Phoenix area's recently opened light rail system shows that its 28 stations are located in areas of significant white, black and Hispanic segregation, and there is a clear concentration of renters over owners around most stations. There is little indication of statistically significant change in segregation or population concentration around the stations, indicating a lack of near term impact of light rail on the region's overall demographics.
ContributorsFolch, David C. (Author) / Rey, Sergio J (Thesis advisor) / Anselin, Luc (Committee member) / Murray, Alan T. (Committee member) / Arizona State University (Publisher)
Created2012
Description
The purpose of this study is to first investigate the role of political socialization on young men and women and what motivates them to become politically active and make the ultimate decision to run for elected office. These effects include parental attitudes, exposure to political shows and news sources, participation in voluntary organizations, and overall community involvement. After understanding these direct and indirect effects of political socialization, I can attempt to explain the causes for the gender gap in political ambition \u2014 meaning that significantly more men are running for elected office compared to women.
ContributorsOsgood, Shannon Marie (Author) / Woodall, Gina (Thesis director) / Herrera, Richard (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Public Affairs (Contributor) / School of Politics and Global Studies (Contributor)
Created2015-05
Description
The Undoing Project is an ongoing educational feminist YouTube channel that serves as an introduction to feminism and feminist theory. The objective for this project is to present feminist theory and feminist ideology in an accessible and entertaining way. Through this project I sought to accomplish three goals: to challenge the negative image of feminism, bridge the gap between the language of academia and the public, and to acknowledge and unlearn ingrained prejudices. The videos focus on theory, history, legislation, current events, and pop culture. The initial project consists of ten videos addressing the feminist wave models, a brief history of the feminist movement, and discussions of concepts like hegemony, intersectionality, masculinity, femininity, and race.
ContributorsBuchholtz, Kaylee Marie (Author) / Brian, Jennifer (Thesis director) / Grzanka, Patrick (Committee member) / Brouwer, Dan (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Social Transformation (Contributor) / Department of English (Contributor)
Created2015-05
Description
Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine has been notoriously difficult to produce. To overcome this, a vaccine using non-structural protein 3 (NS3) as a target to elicit a T cell specific immune response is thought to be a possible strategy for eliciting a protective immune response against hepatitis C infection. In this paper, a recombinant strain of measles virus (MV) that expresses HCV NS3 protein was analyzed. The replication fitness of this recombinant virus also indicates that this construct replicates at a higher rate than parental measles strain. It is also demonstrated through western blot analysis of protein expression and immunofluorescence that this recombinant virus expresses both the inserted HCV NS3 protein, as well as native measles proteins.
ContributorsWoell, Dana Marie (Author) / Reyes del Valle, Jorge (Thesis director) / Nickerson, Cheryl (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05