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Description
The Multiple Antibiotic Resistance Regulator Family (MarR) are transcriptional regulators, many of which forms a dimer. Transcriptional regulation provides bacteria a stabilized responding system to ensure the bacteria is able to efficiently adapt to different environmental conditions. The main function of the MarR family is to create multiple antibiotic resistance from a mutated protein; this process occurs when the MarR regulates an operon. We hypothesized that different transcriptional regulator genes have interactions with each other. It is known that Salmonella pagC transcription is activated by three regulators, i.e., SlyA, MprA, and PhoP. Bacterial Adenylate Cyclase-based Two-Hybrid (BACTH) system was used to research the protein-protein interactions in SlyA, MprA, and PhoP as heterodimers and homodimers in vivo. Two fragments, T25 and T18, that lack endogenous adenylate cyclase activity, were used for construction of chimeric proteins and reconstruction of adenylate cyclase activity was tested. The significant adenylate cyclase activities has proved that SlyA is able to form homodimers. However, weak adenylate cyclase activities in this study has proved that MprA and PhoP are not likely to form homodimers, and no protein-protein interactions were detected in between SlyA, MprA and PhoP, which no heterodimers have formed in between three transcriptional regulators.
ContributorsTao, Zenan (Author) / Shi, Yixin (Thesis advisor) / Wang, Xuan (Committee member) / Bean, Heather (Committee member) / Arizona State University (Publisher)
Created2018
Description
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is the 10th leading cause of death, worldwide. The prevalence of drug-resistant clinical isolates and the paucity of newly-approved antituberculosis drugs impedes the successful eradication of Mtb. Bacteria commonly use two-component systems (TCS) to sense their environment and genetically modulate adaptive responses. The prrAB TCS is essential in Mtb, thus representing an auspicious drug target; however, the inability to generate an Mtb ΔprrAB mutant complicates investigating how this TCS contributes to pathogenesis. Mycobacterium smegmatis, a commonly used M. tuberculosis genetic surrogate was used here. This work shows that prrAB is not essential in M. smegmatis. During ammonium stress, the ΔprrAB mutant excessively accumulates triacylglycerol lipids, a phenotype associated with M. tuberculosis dormancy and chronic infection. Additionally, triacylglycerol biosynthetic genes were induced in the ΔprrAB mutant relative to the wild-type and complementation strains during ammonium stress. Next, RNA-seq was used to define the M. smegmatis PrrAB regulon. PrrAB regulates genes participating in respiration, metabolism, redox balance, and oxidative phosphorylation. The M. smegmatis ΔprrAB mutant is compromised for growth under hypoxia, is hypersensitive to cyanide, and fails to induce high-affinity respiratory genes during hypoxia. Furthermore, PrrAB positively regulates the hypoxia-responsive dosR TCS response regulator, potentially explaining the hypoxia-mediated growth defects in the ΔprrAB mutant. Despite inducing genes encoding the F1F0 ATP synthase, the ΔprrAB mutant accumulates significantly less ATP during aerobic, exponential growth compared to the wild-type and complementation strains. Finally, the M. smegmatis ΔprrAB mutant exhibited growth impairment in media containing gluconeogenic carbon sources. M. tuberculosis mutants unable to utilize these substrates fail to establish chronic infection, suggesting that PrrAB may regulate Mtb central carbon metabolism in response to chronic infection. In conclusion, 1) prrAB is not universally essential in mycobacteria; 2) M. smegmatis PrrAB regulates genetic responsiveness to nutrient and oxygen stress; and 3) PrrAB may provide feed-forward control of the DosRS TCS and dormancy phenotypes. The data generated in these studies provide insight into the mycobacterial PrrAB TCS transcriptional regulon, PrrAB essentiality in Mtb, and how PrrAB may mediate stresses encountered by Mtb during the transition to chronic infection.
ContributorsMaarsingh, Jason (Author) / Haydel, Shelley E (Thesis advisor) / Roland, Kenneth (Committee member) / Sandrin, Todd (Committee member) / Bean, Heather (Committee member) / Arizona State University (Publisher)
Created2019
Description
One out of ten women has a difficult time getting or staying pregnant in the United States. Recent studies have identified aging as one of the key factors attributed to a decline in female reproductive health. Existing fertility diagnostic methods do not allow for the non-invasive monitoring of hormone levels across time. In recent years, olfactory sensing has emerged as a promising diagnostic tool for its potential for real-time, non-invasive monitoring. This technology has been proven promising in the areas of oncology, diabetes, and neurological disorders. Little work, however, has addressed the use of olfactory sensing with respect to female fertility. In this work, we perform a study on ten healthy female subjects to determine the volatile signature in biological samples across 28 days, correlating to fertility hormones. Volatile organic compounds (VOCs) present in the air above the biological sample, or headspace, were collected by solid phase microextraction (SPME), using a 50/30 µm divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) coated fiber. Samples were analyzed, using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS). A regression model was used to identify key analytes, corresponding to the fertility hormones estrogen and progesterone. Results indicate shifts in volatile signatures in biological samples across the 28 days, relevant to hormonal changes. Further work includes evaluating metabolic changes in volatile hormone expression as an early indicator of declining fertility, so women may one day be able to monitor their reproductive health in real-time as they age.
ContributorsOng, Stephanie (Author) / Smith, Barbara (Thesis advisor) / Bean, Heather (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2018
Description
For as long as humans have been working, they have been looking for ways to get that work done better, faster, and more efficient. Over the course of human history, mankind has created innumerable spectacular inventions, all with the goal of making the economy and daily life more efficient. Today, innovations and technological advancements are happening at a pace like never seen before, and technology like automation and artificial intelligence are poised to once again fundamentally alter the way people live and work in society. Whether society is prepared or not, robots are coming to replace human labor, and they are coming fast. In many areas artificial intelligence has disrupted entire industries of the economy. As people continue to make advancements in artificial intelligence, more industries will be disturbed, more jobs will be lost, and entirely new industries and professions will be created in their wake. The future of the economy and society will be determined by how humans adapt to the rapid innovations that are taking place every single day. In this paper I will examine the extent to which automation will take the place of human labor in the future, project the potential effect of automation to future unemployment, and what individuals and society will need to do to adapt to keep pace with rapidly advancing technology. I will also look at the history of automation in the economy. For centuries humans have been advancing technology to make their everyday work more productive and efficient, and for centuries this has forced humans to adapt to the modern technology through things like training and education. The thesis will additionally examine the ways in which the U.S. education system will have to adapt to meet the demands of the advancing economy, and how job retraining programs must be modernized to prepare workers for the changing economy.
ContributorsCunningham, Reed P. (Author) / DeSerpa, Allan (Thesis director) / Haglin, Brett (Committee member) / School of International Letters and Cultures (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The purpose of this study was to observe the effectiveness of the phenylalanyl arginine β-naphthylamide dihydrochloride inhibitor and Tween 20 when combined with an antibiotic against Escherichia. coli. As antibiotic resistance becomes more and more prevalent it is necessary to think outside the box and do more than just increase the dosage of currently prescribed antibiotics. This study attempted to combat two forms of antibiotic resistance. The first is the AcrAB efflux pump which is able to pump antibiotics out of the cell. The second is the biofilms that E. coli can form. By using an inhibitor, the pump should be unable to rid itself of an antibiotic. On the other hand, using Tween allows for biofilm formation to either be disrupted or for the biofilm to be dissolved. By combining these two chemicals with an antibiotic that the efflux pump is known to expel, low concentrations of each chemical should result in an equivalent or greater effect on bacteria compared to any one chemical in higher concentrations. To test this hypothesis a 96 well plate BEC screen test was performed. A range of antibiotics were used at various concentrations and with varying concentrations of both Tween and the inhibitor to find a starting point. Following this, Erythromycin and Ciprofloxacin were picked as the best candidates and the optimum range of the antibiotic, Tween, and inhibitor were established. Finally, all three chemicals were combined to observe the effects they had together as opposed to individually or paired together. From the results of this experiment several conclusions were made. First, the inhibitor did in fact increase the effectiveness of the antibiotic as less antibiotic was needed if the inhibitor was present. Second, Tween showed an ability to prevent recovery in the MBEC reading, showing that it has the ability to disrupt or dissolve biofilms. However, Tween also showed a noticeable decrease in effectiveness in the overall treatment. This negative interaction was unable to be compensated for when using the inhibitor and so the hypothesis was proven false as combining the three chemicals led to a less effective treatment method.
ContributorsPetrovich Flynn, Chandler James (Author) / Misra, Rajeev (Thesis director) / Bean, Heather (Committee member) / Perkins, Kim (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The inherent risk in testing drugs has been hotly debated since the government first started regulating the drug industry in the early 1900s. Who can assume the risks associated with trying new pharmaceuticals is unclear when looked at through society's lens. In the mid twentieth century, the US Food and Drug Administration (FDA) published several guidance documents encouraging researchers to exclude women from early clinical drug research. The motivation to publish those documents and the subsequent guidance documents in which the FDA and other regulatory offices established their standpoints on women in drug research may have been connected to current events at the time. The problem of whether women should be involved in drug research is a question of who can assume risk and who is responsible for disseminating what specific kinds of information. The problem tends to be framed as one that juxtaposes the health of women and fetuses and sets their health as in opposition. That opposition, coupled with the inherent uncertainty in testing drugs, provides for a complex set of issues surrounding consent and access to information.
ContributorsMeek, Caroline Jane (Author) / Maienschein, Jane (Thesis director) / Brian, Jennifer (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This research compares shifts in a SuperSpec titanium nitride (TiN) kinetic inductance detector's (KID's) resonant frequency with accepted models for other KIDs. SuperSpec, which is being developed at the University of Colorado Boulder, is an on-chip spectrometer designed with a multiplexed readout with multiple KIDs that is set up for a broadband transmission of these measurements. It is useful for detecting radiation in the mm and sub mm wavelengths which is significant since absorption and reemission of photons by dust causes radiation from distant objects to reach us in infrared and far-infrared bands. In preparation for testing, our team installed stages designed previously by Paul Abers and his group into our cryostat and designed and installed other parts necessary for the cryostat to be able to test devices on the 250 mK stage. This work included the design and construction of additional parts, a new setup for the wiring in the cryostat, the assembly, testing, and installation of several stainless steel coaxial cables for the measurements through the devices, and other cryogenic and low pressure considerations. The SuperSpec KID was successfully tested on this 250 mK stage thus confirming that the new setup is functional. Our results are in agreement with existing models which suggest that the breaking of cooper pairs in the detector's superconductor which occurs in response to temperature, optical load, and readout power will decrease the resonant frequencies. A negative linear relationship in our results appears, as expected, since the parameters are varied only slightly so that a linear approximation is appropriate. We compared the rate at which the resonant frequency responded to temperature and found it to be close to the expected value.
ContributorsDiaz, Heriberto Chacon (Author) / Mauskopf, Philip (Thesis director) / McCartney, Martha (Committee member) / Department of Physics (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This paper considers what factors influence student interest, motivation, and continued engagement. Studies show anticipated extrinsic rewards for activity participation have been shown to reduce intrinsic value for that activity. This might suggest that grade point average (GPA) has a similar effect on academic interests. Further, when incentives such as scholarships, internships, and careers are GPA-oriented, students must adopt performance goals in courses to guarantee success. However, performance goals have not been shown to correlated with continued interest in a topic. Current literature proposes that student involvement in extracurricular activities, focused study groups, and mentored research are crucial to student success. Further, students may express either a fixed or growth mindset, which influences their approach to challenges and opportunities for growth. The purpose of this study was to collect individual cases of students' experiences in college. The interview method was chosen to collect complex information that could not be gathered from standard surveys. To accomplish this, questions were developed based on content areas related to education and motivation theory. The content areas included activities and meaning, motivation, vision, and personal development. The developed interview method relied on broad questions that would be followed by specific "probing" questions. We hypothesize that this would result in participant-led discussions and unique narratives from the participant. Initial findings suggest that some of the questions were effective in eliciting detailed responses, though results were dependent on the interviewer. From the interviews we find that students value their group involvements, leadership opportunities, and relationships with mentors, which parallels results found in other studies.
ContributorsAbrams, Sara (Author) / Hartwell, Lee (Thesis director) / Correa, Kevin (Committee member) / Department of Psychology (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This study estimates the capitalization effect of golf courses in Maricopa County using the hedonic pricing method. It draws upon a dataset of 574,989 residential transactions from 2000 to 2006 to examine how the aesthetic, non-golf benefits of golf courses capitalize across a gradient of proximity measures. The measures for amenity value extend beyond home adjacency and include considerations for homes within a range of discrete walkability buffers of golf courses. The models also distinguish between public and private golf courses as a proxy for the level of golf course access perceived by non-golfers. Unobserved spatial characteristics of the neighborhoods around golf courses are controlled for by increasing the extent of spatial fixed effects from city, to census tract, and finally to 2000 meter golf course ‘neighborhoods.’ The estimation results support two primary conclusions. First, golf course proximity is found to be highly valued for adjacent homes and homes up to 50 meters way from a course, still evident but minimal between 50 and 150 meters, and insignificant at all other distance ranges. Second, private golf courses do not command a higher proximity premia compared to public courses with the exception of homes within 25 to 50 meters of a course, indicating that the non-golf benefits of courses capitalize similarly, regardless of course type. The results of this study motivate further investigation into golf course features that signal access or add value to homes in the range of capitalization, particularly for near-adjacent homes between 50 and 150 meters thought previously not to capitalize.
ContributorsJoiner, Emily (Author) / Abbott, Joshua (Thesis director) / Smith, Kerry (Committee member) / Economics Program in CLAS (Contributor) / School of Sustainability (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Nuclear weapons possess enormous potential to inflict damage on our world. The majority of countries in the world denounce the proliferation of these weapons, but a minority of countries have a desire to proliferate. This essay analyzes the impact of regime type and alliance strength to a nuclear state on protégé proliferation decisions. Prior research focuses on single factors in proliferation decisions and fails to take in to account the multi-faceted factors that influence the international system that states operate in. The analysis finds that regime type gives an indication about a state’s likelihood to proliferate, but does not explain proliferation choices comprehensively. Alliance strength plays a large role in a state’s security calculations and must be analyzed in conjunction to regime type to understand proliferation decisions.
ContributorsHsu, Kai Nalu (Author) / Wright, Thorin (Thesis director) / Thies, Cameron (Committee member) / W.P. Carey School of Business (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05