Matching Items (72)
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 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
Public Private Partnerships (PPP) have been in use for years in the United Kingdom, Europe, Australia and for a shorter time here in the United States. Typical PPP infrastructure projects include a multi-year term of operation in addition to constructing the structural features to be used. Early studies are proving PPP delivery methods to be effective at construction cost containment. An examination of the key elements that constitute the early stage negotiation reveal that there is room for negotiation created by the governing documentation while maintaining a competitive environment that brings the best value available to the Public entity. This paper will examine why PPP's are effective during this critical construction period of the facilities life cycle. It is the intent of this study to examine why the features and outcomes of more or less negotiation and the degree of rigor associated with it.
ContributorsMaddex, William E (Author) / Chasey, Allan (Thesis advisor) / El Asmar, Mounir (Committee member) / Pendyala, Ram (Committee member) / Arizona State University (Publisher)
Created2012
Description
Public-Private Partnerships (P3) in North America have become a trend in the past two decades and are gaining attention in the transportation industry with some large scale projects being delivered by this approach. This is due to the need for alternative funding sources for public projects and for improved efficiency of these projects in order to save time and money. Several research studies have been done, including mature markets in Europe and Australia, on the cost and schedule performance of transportation projects but no similar study has been conducted in North America. This study focuses on cost and schedule performance of twelve P3 transportation projects during their construction phase, costing over $100 million each, consisting of roads and bridges only with no signature tunnels. The P3 approach applied in this study is the Design-Build-Finance-Operate-Maintain (DBFOM) model and the results obtained are compared with similar research studies on North American Design-Build (DB) and Design-Bid-Build (DBB) projects. The schedule performance for P3 projects in this study was found to be -0.23 percent versus estimated as compared to the 4.34 percent for the DBB projects and 11.04 percent for the DB projects in the Shrestha study, indicating P3 projects are completed in less time than other methods. The cost performance in this study was 0.81 percent for the P3 projects while in the Shrestha study the average cost increase for the four DB projects was found to be 1.49 percent while for the DBB projects it was 12.71 percent, again indicating P3 projects reduce cost compared to other delivery approaches. The limited number of projects available for this study does not allow us to draw an explicit conclusion on the performance of P3s in North America but paves the way for future studies to explore more data as it becomes available. However, the results in this study show that P3 projects have good cost and schedule adherence to the contract requirements. This study gives us an initial comparison of P3 performance with the more traditional approach and shows us the empirical benefits and limitations of the P3 approach in the highway construction industry.
ContributorsBansal, Ankita (Author) / Chasey, Allan (Thesis advisor) / Gibson, Edd (Committee member) / Pendyala, Ram (Committee member) / Arizona State University (Publisher)
Created2012
Description
Along with the number of technologies that have been introduced over a few years ago, gesture-based human-computer interactions are becoming the new phase in encompassing the creativity and abilities for users to communicate and interact with devices. Because of how the nature of defining free-space gestures influence user's preference and the length of usability of gesture-driven devices, defined low-stress and intuitive gestures for users to interact with gesture recognition systems are necessary to consider. To measure stress, a Galvanic Skin Response instrument was used as a primary indicator, which provided evidence of the relationship between stress and intuitive gestures, as well as user preferences towards certain tasks and gestures during performance. Fifteen participants engaged in creating and performing their own gestures for specified tasks that would be required during the use of free-space gesture-driven devices. The tasks include "activation of the display," scroll, page, selection, undo, and "return to main menu." They were also asked to repeat their gestures for around ten seconds each, which would give them time and further insight of how their gestures would be appropriate or not for them and any given task. Surveys were given at different time to the users: one after they had defined their gestures and another after they had repeated their gestures. In the surveys, they ranked their gestures based on comfort, intuition, and the ease of communication. Out of those user-ranked gestures, health-efficient gestures, given that the participants' rankings were based on comfort and intuition, were chosen in regards to the highest ranked gestures.
ContributorsLam, Christine (Author) / Walker, Erin (Thesis director) / Danielescu, Andreea (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor) / School of Arts, Media and Engineering (Contributor) / Department of English (Contributor) / Computing and Informatics Program (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
Description
G3Box's 2013 Marketing Plan outlines a strategic plan and short term operational strategies for the company. The document includes a discussion of the company's decision to enter the market for healthcare facilities in developing counties, and a situation assessment of the market conditions. G3Box is targeting small and large NGOs that currently provide healthcare facilities in developing countries. The market size for healthcare aid in developing countries is estimated to be $1.7 billion. The plan also analyses the customer's value chain and buying cycle by using voice of the customer data. The strategic position analysis profiles G3Box's competition and discusses the company's differential advantage versus other options for healthcare facilities in developing countries. Next the document discusses G3Box's market strategy and implementation, along with outlining a value proposition for the company. G3Box has two objectives for 2013: 1) Increase sales revenue to $1.3 million and 2) increase market presence to 25%. In order to reach these objectives, G3Box has developed a primary and secondary strategic focus for each objective. The primary strategies are relationship selling and online marketing. The secondary strategies are developing additional value-added activities and public relations.
ContributorsWalters, John (Author) / Denning, Michael (Thesis director) / Ostrom, Lonnie (Committee member) / Carroll, James (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
Description
The majority of the 52 photovoltaic installations at ASU are governed by power purchase agreements (PPA) that set a fixed per kilowatt-hour rate at which ASU buys power from the system owner over the period of 15-20 years. PPAs require accurate predictions of the system output to determine the financial viability of the system installations as well as the purchase price. The research was conducted using PPAs and historical solar power production data from the ASU's Energy Information System (EIS). The results indicate that most PPAs slightly underestimate the annual energy yield. However, the modeled power output from PVsyst indicates that higher energy outputs are possible with better system monitoring.
ContributorsVulic, Natasa (Author) / Bowden, Stuart (Thesis director) / Bryan, Harvey (Committee member) / Sharma, Vivek (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12
Description
The 21st century engineer will face a diverse set of challenges spread out along a broad spectrum of disciplines. Among others, the fields of energy, healthcare, cyberspace, virtual reality, and neuroscience require monumental efforts by the new generation of engineers to meet the demands of a growing society. However the most important, and likely the most under recognized, challenge lies in developing advanced personalized learning. It is the core foundation from which the rest of the challenges can be accomplished. Without an effective method of teaching engineering students how to realize these grand challenges, the knowledge pool from which to draw new innovations and discoveries will be greatly diminished. This paper introduces the Inventors Workshop (IW), a hands-on, passion-based approach to personalized learning. It is intended to serve as a manual that will inform the next generation of student leaders and inventioneers about the core concepts the Inventors Workshop was built upon, and how to continue improvement into the future. Due to the inherent complexities in the grand challenge of personalized learning, the IW has developed a multifaceted solution that is difficult to explain in a single phrase. To enable comprehension of the IW's full vision, the process undergone to date of establishing and expanding the IW is described. In addition, research has been conducted to determine a variety of paths the Inventors Workshop may utilize in future expansion. Each of these options is explored and related to the core foundations of the IW to assist future leaders and partners in effectively improving personalized learning at ASU and beyond.
ContributorsEngelhoven, V. Logan (Author) / Burleson, Winslow (Thesis director) / Peck, Sidnee (Committee member) / Fortun, A. L. Cecil (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor)
Created2012-12