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It is important to consider factors that contribute to successful fertilization and the development of viable offspring. Better understanding the factors that contribute to infertility can be used to assist in the development of viable offspring, especially for human beings looking to successfully reproduce. Identifying paternal effect genes, genes that come from the father, introduces more targets that can be manipulated to produce specific reproductive effects. Use of Drosophila melanogaster as a model to study reproduction has increased, in part, due to the use of the GAL4 system. In this system, the GAL4 gene encodes an 881 amino acid protein that binds to the 4-site Upstream Activating Sequence (UAS) to induce transcription of the gene of interest. These sequences constitute the two components of the system: the driver (GAL4) and the responder (gene of interest) \u2014 each of which is maintained as a separate parental line. Effects of the GAL4 driver line "driving" transcription of the responder can be assessed by examining the offspring. One of the more common uses of the GAL4 system involves analyzing phenotypic effects of reducing or eliminating expression of a target gene through the induction of RNAi transcription, which often results in toxicity, lethality, or reduced viability. Utilizing these principles, we strove to demonstrate the effect of knocking down the expression of testis-specific sperm-leucyl-aminopeptidases gene CG13340 on progeny by inducing expression of RNAi with two distinct GAL4 driver lines - one with a nonspecific actin-binding activation sequence and the other with a testis-specific activation sequence. Comparison of both GAL4 driver lines to crosses using N01 wild type ("wt") flies verify that inducing RNAi transcription using the GAL4 system results in reduction of proper offspring development. Further studies using D. melanogaster and the GAL4 system can improve knowledge of factors contributing to male fertility and also be applied to better understand mammalian, specifically human, fertility.
ContributorsEvans, Donna Marie (Author) / Karr, Timothy L. (Thesis director) / Roland, Kenneth (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of English (Contributor)
Created2014-05
Description
Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cities in the Global South face rapid urbanization challenges and often suffer an acute lack of infrastructure and governance capacities. Smart Cities Mission, in India, launched in 2015, aims to offer a novel approach for urban renewal of 100 cities following an area‐based development approach, where the use of ICT and digital technologies is particularly emphasized. This article presents a critical review of the design and implementation framework of this new urban renewal program across selected case‐study cities. The article examines the claims of the so‐called “smart cities” against actual urban transformation on‐ground and evaluates how “inclusive” and “sustainable” these developments are. We quantify the scale and coverage of the smart city urban renewal projects in the cities to highlight who the program includes and excludes. The article also presents a statistical analysis of the sectoral focus and budgetary allocations of the projects under the Smart Cities Mission to find an inherent bias in these smart city initiatives in terms of which types of development they promote and the ones it ignores. The findings indicate that a predominant emphasis on digital urban renewal of selected precincts and enclaves, branded as “smart cities,” leads to deepening social polarization and gentrification. The article offers crucial urban planning lessons for designing ICT‐driven urban renewal projects, while addressing critical questions around inclusion and sustainability in smart city ventures.`
ContributorsPraharaj, Sarbeswar (Author)
Created2021-05-07
Description
Attitudes and habits are extremely resistant to change, but a disruption of the magnitude of the COVID-19 pandemic has the potential to bring long-term, massive societal changes. During the pandemic, people are being compelled to experience new ways of interacting, working, learning, shopping, traveling, and eating meals. Going forward, a critical question is whether these experiences will result in changed behaviors and preferences in the long term. This paper presents initial findings on the likelihood of long-term changes in telework, daily travel, restaurant patronage, and air travel based on survey data collected from adults in the United States in Spring 2020. These data suggest that a sizable fraction of the increase in telework and decreases in both business air travel and restaurant patronage are likely here to stay. As for daily travel modes, public transit may not fully recover its pre-pandemic ridership levels, but many of our respondents are planning to bike and walk more than they used to. These data reflect the responses of a sample that is higher income and more highly educated than the US population. The response of these particular groups to the COVID-19 pandemic is perhaps especially important to understand, however, because their consumption patterns give them a large influence on many sectors of the economy.
ContributorsConway, Matthew Wigginton (Author) / Salon, Deborah (Author) / da Silva, Denise Capasso (Author) / Mirtich, Laura Christine (Author)
Created2020-09-03
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
The emergence of invasive non-Typhoidal Salmonella (iNTS) infections belonging to sequence type (ST) 313 are associated with severe bacteremia and high mortality in sub-Saharan Africa. Distinct features of ST313 strains include resistance to multiple antibiotics, extensive genomic degradation, and atypical clinical diagnosis including bloodstream infections, respiratory symptoms, and fever. Herein, I report the use of dynamic bioreactor technology to profile the impact of physiological fluid shear levels on the pathogenesis-related responses of ST313 pathovar, 5579. I show that culture of 5579 under these conditions induces profoundly different pathogenesis-related phenotypes than those normally observed when cultures are grown conventionally. Surprisingly, in response to physiological fluid shear, 5579 exhibited positive swimming motility, which was unexpected, since this strain was initially thought to be non-motile. Moreover, fluid shear altered the resistance of 5579 to acid, oxidative and bile stress, as well as its ability to colonize human colonic epithelial cells. This work leverages from and advances studies over the past 16 years in the Nickerson lab, which are at the forefront of bacterial mechanosensation and further demonstrates that bacterial pathogens are “hardwired” to respond to the force of fluid shear in ways that are not observed during conventional culture, and stresses the importance of mimicking the dynamic physical force microenvironment when studying host-pathogen interactions. The results from this study lay the foundation for future work to determine the underlying mechanisms operative in 5579 that are responsible for these phenotypic observations.
ContributorsCastro, Christian (Author) / Nickerson, Cheryl A. (Thesis advisor) / Ott, C. Mark (Committee member) / Roland, Kenneth (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2016
Description
Invasive salmonellosis caused by Salmonella enterica serovar Typhimurium ST313 is a major health crisis in sub-Saharan Africa, with multidrug resistance and atypical clinical presentation challenging current treatment regimens and resulting in high mortality. Moreover, the increased risk of spreading ST313 pathovars worldwide is of major concern, given global public transportation networks and increased populations of immunocompromised individuals (as a result of HIV infection, drug use, cancer therapy, aging, etc). While it is unclear as to how Salmonella ST313 strains cause invasive disease in humans, it is intriguing that the genomic profile of some of these pathovars indicates key differences between classic Typhimurium (broad host range), but similarities to human-specific typhoidal Salmonella Typhi and Paratyphi. In an effort to advance fundamental understanding of the pathogenesis mechanisms of ST313 in humans, I report characterization of the molecular genetic, phenotypic and virulence profiles of D23580 (a representative ST313 strain). Preliminary studies to characterize D23580 virulence, baseline stress responses, and biochemical profiles, and in vitro infection profiles in human surrogate 3-D tissue culture models were done using conventional bacterial culture conditions; while subsequent studies integrated a range of incrementally increasing fluid shear levels relevant to those naturally encountered by D23580 in the infected host to understand the impact of biomechanical forces in altering these characteristics. In response to culture of D23580 under these conditions, distinct differences in transcriptional biosignatures, pathogenesis-related stress responses, in vitro infection profiles and in vivo virulence in mice were observed as compared to those of classic Salmonella pathovars tested.
Collectively, this work represents the first characterization of in vivo virulence and in vitro pathogenesis properties of D23580, the latter using advanced human surrogate models that mimic key aspects of the parental tissue. Results from these studies highlight the importance of studying infectious diseases using an integrated approach that combines actions of biological and physical networks that mimic the host-pathogen microenvironment and regulate pathogen responses.
Collectively, this work represents the first characterization of in vivo virulence and in vitro pathogenesis properties of D23580, the latter using advanced human surrogate models that mimic key aspects of the parental tissue. Results from these studies highlight the importance of studying infectious diseases using an integrated approach that combines actions of biological and physical networks that mimic the host-pathogen microenvironment and regulate pathogen responses.
ContributorsYang, Jiseon (Author) / Nickerson, Cheryl A. (Thesis advisor) / Chang, Yung (Committee member) / Stout, Valerie (Committee member) / Ott, C Mark (Committee member) / Roland, Kenneth (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2015
Description
In sub-Saharan Africa, an invasive form of nontyphoidal Salmonella (iNTS) belonging to sequence type (ST)313 has emerged as a major public health concern causing widespread bacteremia and mortality in children with malaria and adults with HIV. Clinically, ST313 pathovars are characterized by the absence of gastroenteritis, which is commonly found in “classical” nontyphoidal Salmonella (NTS), along with multidrug resistance, pseudogene formation, and chromosome degradation. There is an urgent need to understand the biological and physical factors that regulate the disease causing properties of ST313 strains. Previous studies from our lab using dynamic Rotating Wall Vessel (RWV) bioreactor technology and “classical” NTS strain χ3339 showed that physiological fluid shear regulates gene expression, stress responses and virulence in unexpected ways that are not observed using conventional shake and static flask conditions, and in a very different manner as compared to ST313 strain D23580. Leveraging from these findings, the current study was the first to report the effect of fluid shear on the pathogenesis-related stress responses of S. Typhimurium ST313 strain A130, which evolved earlier than D23580 within the ST313 clade. A130 displayed enhanced resistance to acid, oxidative and bile stresses when cultured in the high fluid shear (HFS) control condition relative to the low fluid shear (LFS) condition in stationary phase using Lennox Broth (LB) as the culture medium. The greatest magnitude of the survival benefit conferred by high fluid shear was observed in response to oxidative and acid stresses. No differences were observed for thermal and osmotic stresses. Based on previous findings from our laboratory, we also assessed how the addition of phosphate or magnesium ions to the culture medium altered the acid or oxidative stress responses of A130 grown in the RWV. Addition of either
phosphate or magnesium to the culture medium abrogated the fluid shear-related differences observed for A130 in LB medium for the acid or oxidative stress responses, respectively. Collectively, these findings indicate that like other Salmonella strains assessed thus far by our team, A130 responds to differences in physiological fluid shear, and that ion concentrations can modulate those responses.
phosphate or magnesium to the culture medium abrogated the fluid shear-related differences observed for A130 in LB medium for the acid or oxidative stress responses, respectively. Collectively, these findings indicate that like other Salmonella strains assessed thus far by our team, A130 responds to differences in physiological fluid shear, and that ion concentrations can modulate those responses.
ContributorsGutierrez-Jensen, Ami Dave (Author) / Nickerson, Cheryl A. (Thesis advisor) / Barrila, Jennifer (Thesis advisor) / Ott, C. M. (Committee member) / Roland, Kenneth (Committee member) / Arizona State University (Publisher)
Created2017
Description
Urban areas across the Unites States are facing a housing affordability crisis. One approach some cities and states have taken is to reduce or eliminate single-family zoning. Single-family zoning prevents the construction of more-affordable apartments in vast swaths of the American urban landscape. This policy shift has already occurred in Minneapolis, Sacramento, and Oregon, and is under discussion in California, Massachusetts, and North Carolina, among others. Independent of any effects on housing affordability, changes to land use will have effects on transport. I evaluate these effects using a microsimulation framework. In order for land use policies to have an effect on transport, they need to first have an effect on land use, so I first build an economic model to simulate where development will occur given a loosening of single-family zoning. Transport outcomes will vary depending on which households live in which parts of the region, so I use an equilibrium sorting model to forecast how residents will re-sort across the region in response to the land use changes induced by new land-use policies. This model also jointly forecasts how many vehicles each household will choose to own. Finally, I apply an activity-based travel demand microsimulation model to forecast the changes in transport associated with the forecast changes from the previous models. I find that while there is opportunity for economically-feasible redevelopment of single-family homes into multifamily structures, the amount of redevelopment that will occur varies greatly depending on the exact expectations of developers about future market conditions. Redevelopment is focused in higher-income neighborhoods. The transport effects of the redevelopment are minimal. Average car ownership across the region does not change hardly at all, although residents of new housing units do have somewhat lower car ownership. Vehicles kilometers traveled, mode choice, and congestion change very little as well. This does not mean that upzoning does not affect transport in general, but that more nuanced proposals may be necessary to promote desirable transport outcomes. Alternatively, the results suggest that upzoning will not worsen transport outcomes, promising for those who support upzoning on affordability grounds.
ContributorsConway, Matthew Wigginton (Author) / Salon, Deborah (Thesis advisor) / Pfeiffer, Deirdre (Committee member) / Fotheringham, A Stewart (Committee member) / van Eggermond, Michael AB (Committee member) / Arizona State University (Publisher)
Created2021
Description
This work suggests an effective approach to fabricate reduced graphene oxide-based carbon (RGO/C) composite films. The carbonization of graphene oxide-reinforced polyimide (GO/PI) composite films was investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The crystalline structures and carbonized mechanism of the RGO/C composite films were investigated in detail by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Furthermore, the carbonization yields were improved due to the catalytic effects of RGO. These RGO/C composite films exhibited obvious structural orientations by SEM investigation of their cross sections.
ContributorsNiu, Yongan (Author) / Zhang, Xin (Author) / Zhao, Jiupeng (Author) / Tian, Yanqing (Author) / Yan, Xiangqiao (Author) / Li, Yao (Author) / Biodesign Institute (Contributor)
Created2014-04-11