Matching Items (506)
Description
Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector has been reevaluated. To evaluate the safety and efficacy of VACV, we study the interactions between VACV and the host innate immune system, especially the type I interferon (IFN) signaling pathways. In this work, we evaluated the role of protein kinase R (PKR) and Adenosine Deaminase Acting on RNA 1(ADAR1), which are induced by IFN, in VACV infection. We found that PKR is necessary but is not sufficient to activate interferon regulatory factor 3 (IRF3) in the induction of type I IFN; and the activation of the stress-activated protein kinase/ c-Jun NH2-terminal kinase is required for the PKR-dependent activation of IRF3 during VACV infection. Even though PKR was found to have an antiviral effect in VACV, ADAR1 was found to have a pro-viral effect by destabilizing double stranded RNA (dsRNA), rescuing VACVΔE3L, VACV deleted of the virulence factor E3L, when provided in trans. With the lessons we learned from VACV and host cells interaction, we have developed and evaluated a safe replication-competent VACV vaccine vector for HIV. Our preliminary results indicate that our VACV vaccine vector can still induce the IFN pathway while maintaining the ability to replicate and to express the HIV antigen efficiently. This suggests that this VACV vector can be used as a safe and efficient vaccine vector for HIV.
ContributorsHuynh, Trung Phuoc (Author) / Jacobs, Bertram L (Thesis advisor) / Hogue, Brenda (Committee member) / Chang, Yung (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2013
Description
How a colony regulates the division of labor to forage for nutritional resources while accommodating for changes in colony demography is a fundamental question in the sociobiology of social insects. In honey bee, Apis mellifera, brood composition impacts the division of labor, but it is unknown if colonies adjust the allocation of foragers to carbohydrate and protein resources based on changes in the age demography of larvae and the pheromones they produce. Young and old larvae produce pheromones that differ in composition and volatility. In turn, nurses differentially provision larvae, feeding developing young worker larvae a surplus diet that is more queen-like in protein composition and food availability, while old larvae receive a diet that mimics the sugar composition of the queen larval diet but is restrictively fed instead of provided ad lib. This research investigated how larval age and the larval pheromone e-β ocimene (eβ) impact foraging activity and foraging load. Additional cage studies were conducted to determine if eβ interacts synergistically with queen mandibular pheromone (QMP) to suppress ovary activation and prime worker physiology for nursing behavior. Lastly, the priming effects of larval age and eβ on worker physiology and the transition from in-hive nursing tasks to outside foraging were examined. Results indicate that workers differentially respond to larvae of different ages, likely by detecting changes in the composition of the pheromones they emit. This resulted in adjustments to the foraging division of labor (pollen vs. nectar) to ensure that the nutritional needs of the colony's brood were met. For younger larvae and eβ, this resulted in a bias favoring pollen collection. The cage studies reveal that both eβ and QMP suppressed ovary activation, but the larval pheromone was more effective. Maturing in an environment of young or old larvae primed bees for nursing and impacted important endocrine titers involved in the transition to foraging, so bees maturing in the presence of larvae foraged earlier than control bees reared with no brood.
ContributorsTraynor, Kirsten S. (Author) / Page, Robert E. (Thesis advisor) / Hölldobler, Berthold (Committee member) / Pratt, Stephen (Committee member) / Liebig, Jürgen (Committee member) / Brent, Colin (Committee member) / Baluch, Page (Committee member) / Arizona State University (Publisher)
Created2014
Description
Engineered nanoparticles (NP; 10-9 m) have found use in a variety of consumer goods and medical devices because of the unique changes in material properties that occur when synthesized on the nanoscale. Although many definitions for nanoparticle exist, from the perspective of size, nanoparticle is defined as particles with diameters less than 100 nm in any external dimension. Examples of their use include titanium dioxide added as a pigment in products intended to be ingested by humans, silicon dioxide NPs are used in foods as an anticaking agent, and gold or iron oxide NPs can be used as vectors for drug delivery or contrast agents for specialized medical imaging. Although the intended use of these NPs is often to improve human health, it has come to the attention of investigators that NPs can have unintended or even detrimental effects on the organism. This work describes one such unintended effect of NP exposure from the perspective of exposure via the oral route. First, this Dissertation will explain an event referred to as brush border disruption that occurred after nanoparticles interacted with an in vitro model of the human intestinal epithelium. Second, this Dissertation will identify and characterize several consumer goods that were shown to contain titanium dioxide that are intended to be ingested. Third, this Dissertation shows that sedimentation due to gravity does not artifactually result in disruption of brush borders as a consequence of exposure to food grade titanium dioxide in vitro. Finally, this Dissertation will demonstrate that iron oxide nanoparticles elicited similar effects after exposure to an in vitro brush border expressing model of the human placenta. Together, these data suggest that brush border disruption is not an artifact of the material/cell culture model, but instead represents a bona fide biological response as a result of exposure to nanomaterial.
ContributorsFaust, James J (Author) / Capco, David G. (Thesis advisor) / Ugarova, Tatiana (Committee member) / Chandler, Douglas (Committee member) / Baluch, Page (Committee member) / Herman, Richard (Committee member) / Arizona State University (Publisher)
Created2014
Description
A novel clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) tool for simultaneous gene editing and regulation was designed and tested. This study used the CRISPR-associated protein 9 (Cas9) endonuclease in complex with a 14-nucleotide (nt) guide RNA (gRNA) to repress a gene of interest using the Krüppel associated box (KRAB) domain, while also performing a separate gene modification using a 20-nt gRNA targeted to a reporter vector. DNA Ligase IV (LIGIV) was chosen as the target for gene repression, given its role in nonhomologous end joining, a common DNA repair process that competes with the more precise homology-directed repair (HDR).
To test for gene editing, a 20-nt gRNA was designed to target a disrupted enhanced green fluorescent protein (EGFP) gene present in a reporter vector. After the gRNA introduced a double-stranded break, cells attempted to repair the cut site via HDR using a DNA template within the reporter vector. In the event of successful gene editing, the EGFP sequence was restored to a functional state and green fluorescence was detectable by flow cytometry. To achieve gene repression, a 14-nt gRNA was designed to target LIGIV. The gRNA included a com protein recruitment domain, which recruited a Com-KRAB fusion protein to facilitate gene repression via chromatin modification of LIGIV. Quantitative polymerase chain reaction was used to quantify repression.
This study expanded upon earlier advancements, offering a novel and versatile approach to genetic modification and transcriptional regulation using CRISPR/Cas9. The overall results show that both gene editing and repression were occurring, thereby providing support for a novel CRISPR/Cas system capable of simultaneous gene modification and regulation. Such a system may enhance the genome engineering capabilities of researchers, benefit disease research, and improve the precision with which gene editing is performed.
To test for gene editing, a 20-nt gRNA was designed to target a disrupted enhanced green fluorescent protein (EGFP) gene present in a reporter vector. After the gRNA introduced a double-stranded break, cells attempted to repair the cut site via HDR using a DNA template within the reporter vector. In the event of successful gene editing, the EGFP sequence was restored to a functional state and green fluorescence was detectable by flow cytometry. To achieve gene repression, a 14-nt gRNA was designed to target LIGIV. The gRNA included a com protein recruitment domain, which recruited a Com-KRAB fusion protein to facilitate gene repression via chromatin modification of LIGIV. Quantitative polymerase chain reaction was used to quantify repression.
This study expanded upon earlier advancements, offering a novel and versatile approach to genetic modification and transcriptional regulation using CRISPR/Cas9. The overall results show that both gene editing and repression were occurring, thereby providing support for a novel CRISPR/Cas system capable of simultaneous gene modification and regulation. Such a system may enhance the genome engineering capabilities of researchers, benefit disease research, and improve the precision with which gene editing is performed.
ContributorsChapman, Jennifer E (Author) / Kiani, Samira (Thesis advisor) / Ugarova, Tatiana (Thesis advisor) / Marchant, Gary (Committee member) / Arizona State University (Publisher)
Created2018
Description
Breast microcalcifications are a potential indicator of cancerous tumors. Current visualization methods are either uncomfortable or impractical. Impedance measurement studies have been performed, but not in a clinical setting due to a low sensitivity and specificity. We are hoping to overcome this challenge with the development of a highly accurate impedance probe on a biopsy needle. With this technique, microcalcifications and the surrounding tissue could be differentiated in an efficient and comfortable manner than current techniques for biopsy procedures. We have developed and tested a functioning prototype for a biopsy needle using bioimpedance sensors to detect microcalcifications in the human body. In the final prototype a waveform generator sends a sin wave at a relatively low frequency(<1KHz) into the pre-amplifier, which both stabilizes and amplifies the signal. A modified howland bridge is then used to achieve a steady AC current through the electrodes. The voltage difference across the electrodes is then used to calculate the impedance being experienced between the electrodes. In our testing, the microcalcifications we are looking for have a noticeably higher impedance than the surrounding breast tissue, this spike in impedance is used to signal the presence of the calcifications, which are then sampled for examination by radiology.
ContributorsWen, Robert Bobby (Co-author) / Grula, Adam (Co-author) / Vergara, Marvin (Co-author) / Ramkumar, Shreya (Co-author) / Kozicki, Michael (Thesis director) / Ranjani, Kumaran (Committee member) / School of Molecular Sciences (Contributor) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Breastfeeding has been shown by a number of studies to have numerous benefits on both the mother and the infant. Major health organizations such as the World Health Organization (WHO), now agree that breastfeeding should be encouraged and supported in all countries. But like many things, the wheels of the law are slow to catch up with scientific evident. Although breastfeeding is supported, working women do not have the option of breastfeeding without consequences. For example, in 2003, Kirstie Marshall, a then member of parliament in Australia was ejected from the lower house chamber on February 23, for breastfeeding her baby [3]. According to standing order 30 at the time, "Unless by order of the House, no Member of this House shall presume to bring any stranger into any part of the House appropriated to the Members of this House while the House, or a Committee of the whole House, is sitting" [3]. The rules did not specify the age of strangers, so the then 11-day-old baby, Charlotte Louise and her mother were shown the exit door of parliament. She had to choose between being present at times of major discussions or leaving the house to breastfeed her child, she chose to leave. More recent statistics show that developed nations like the US and Australia which also have high rates of women employment had low rates of breastfeeding. This might mean that workplace policies do not favor breastfeeding or expressing milk at work. Fortunately, laws have since been introduced in both the United States and Australia that support breastfeeding at the workplace. The next step would be to access how these laws affect breastfeeding statistics and how variation between these two countries like the paid parental leave in Australia (which is not present in all US states) would affect these numbers.
ContributorsSakala, Lydia (Author) / Alison, Alison (Thesis director) / Reddy, Swapna (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Ketone bodies are produced in the liver from the acetyl CoA derived from fatty acids that cannot enter the Krebs cycle. This is a sub-analysis of a larger study which had numerous outcome markers. This analysis focuses on the relationship between ketone blood levels and cognition. The study looked at the relationship between Time Restricted Feeding (TRF), a method of intermittent fasting. TRF is something that can be easily adapted into an individual’s lifestyle and has been shown to have multiple advantages. This 8-week study began with 23 enrolled participants, but due to COVID-19 only 11 participants could be tested for cognition and blood ketone levels after week 4. All participants had similar ranges of weight, height, age, BMI, hip, and waist measurements at baseline. Moreover, these demographic variables were not related to ketone levels or cognition. The data indicate that ketone bodies increased in participants practicing TRF and that the increase in ketone bodies in the blood, specifically β-hydroxybutyrate was strongly correlated to increased cognitive function. This is consistent with theories that elevated ketone levels allowed for early hunter-gather communities and other mammals to survive prolonged periods of nutrient deprivation while keeping high cognitive function.
ContributorsTaha, Basel Mahmoud (Author) / Johnston, Carol (Thesis director) / Karen, Sweazea (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The purpose of this thesis experiment was to design and create an Acoustically Active Cannula (AAC), which is furnished by a piezoelectric crystal placed at its tip that produces an acoustic navigation signal. I tested the functionality of the cannula in vitro and demonstrated its navigational abilities in vivo in anesthetized pigs. This experiment was based upon ultrasound science and technology, and thus some practical experience with conventional (B-mode) and Doppler ultrasound was achieved as well. The results of bench and experimental animal studies indicated proper functionality of the AAC for identification and spatial navigation of its tip with color Doppler ultrasound imaging.
ContributorsShamsa, Kayvan (Author) / Tyler, William (Thesis director) / Belohlavek, Marek (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The academic study of eSports, or professional competition through the medium of video games, has tended to focus on players' motivations to play and watch eSports as well as marketing concerns of huge eSports corporations. Instead of utilizing marketing or psychology to analyze this phenomenon, I investigate three areas of focus in accordance with available literature: the fans and their characteristics, the design of the game itself, and the relationship between fans and the game's developer. This investigation was conducted by first examining existing literature surrounding eSports fans, then collecting public domain data such as Reddit posts, forum posts, and YouTube videos, and last by studying interviews with developers and players. With this thesis, I apply a fan studies approach to eSports by creating a series of indicators based in each of the three focus areas which can be utilized as a systematic method of evaluating an eSport's popularity and growth.
ContributorsHilliker, Noah Henry (Author) / Ingram-Waters, Mary (Thesis director) / Schmidt, Peter (Committee member) / Anderson, Sky (Committee member) / School of Molecular Sciences (Contributor) / W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
DescriptionThis project is designed to generate enthusiasm for science among refugee students in hopes of inspiring them to continue learning science as well as to help them with their current understanding of their school science subject matter.
ContributorsSipes, Shannon Paige (Author) / O'Flaherty, Katherine (Thesis director) / Gregg, George (Committee member) / School of Molecular Sciences (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12