Matching Items (64)
Description
Cancer is one of the leading causes of death in the world and represents a tremendous burden on patients, families and societies. S. Typhimurium strains are specifically attracted to compounds produced by cancer cells and could overcome the traditional therapeutic barrier. However, a major problem with using live attenuated Salmonella as anti-cancer agents is their toxicity at the dose required for therapeutic efficacy, but reducing the dose results in diminished efficacy. In this project, we explored novel means to reduce the toxicity of the recombinant attenuated Salmonella by genetically engineering those virulence factors to facilitate maximal colonization of tumor tissues and reduced fitness in normal tissues. We have constructed two sets of Salmonella strains. In the first set, each targeted gene was knocked out by deletion of the gene. In the second set, the predicted promoter region of each gene was replaced with a rhamnose-regulated promoter, which will cease the synthesis of these genes in vivo, a rhamnose-free environment.
ContributorsBenson, Lee Samuel (Author) / Kong, Wei (Thesis director) / Martin, Thomas (Committee member) / Lake, Douglas (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Center for Infectious Diseases and Vaccinology (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
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
In the digital humanities, there is a constant need to turn images and PDF files into plain text to apply analyses such as topic modelling, named entity recognition, and other techniques. However, although there exist different solutions to extract text embedded in PDF files or run OCR on images, they typically require additional training (for example, scholars have to learn how to use the command line) or are difficult to automate without programming skills. The Giles Ecosystem is a distributed system based on Apache Kafka that allows users to upload documents for text and image extraction. The system components are implemented using Java and the Spring Framework and are available under an Open Source license on GitHub (https://github.com/diging/).
ContributorsLessios-Damerow, Julia (Contributor) / Peirson, Erick (Contributor) / Laubichler, Manfred (Contributor) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2017-09-28
Description
Because collective cognition emerges from local signaling among group members, deciphering communication systems is crucial to understanding the underlying mechanisms. Alarm signals are widespread in the social insects and can elicit a variety of behavioral responses to danger, but the functional plasticity of these signals has not been well studied. Here we report an alarm pheromone in the ant Temnothorax rugatulus that elicits two different behaviors depending on context. When an ant was tethered inside an unfamiliar nest site and unable to move freely, she released a pheromone from her mandibular gland that signaled other ants to reject this nest as a potential new home, presumably to avoid potential danger. When the same pheromone was presented near the ants' home nest, they were instead attracted to it, presumably to respond to a threat to the colony. We used coupled gas chromatography/mass spectrometry to identify candidate compounds from the mandibular gland and tested each one in a nest choice bioassay. We found that 2,5-dimethylpyrazine was sufficient to induce rejection of a marked new nest and also to attract ants when released at the home nest. This is the first detailed investigation of chemical communication in the leptothoracine ants. We discuss the possibility that this pheromone's deterrent function can improve an emigrating colony's nest site selection performance.
ContributorsSasaki, Takao (Author) / Hoelldobler, Bert (Author) / Millar, Jocelyn G. (Author) / Pratt, Stephen (Author) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / ASU-SFI Center for Biosocial Complex Systems (Contributor) / Center for Social Dynamics and Complexity (Contributor)
Created2014-09-01
Description
Colorectal cancer is the third most common type of cancer that affects both men and women and the second leading cause of death in cancer related deaths[1, 2]. The most common form of treatment is chemotherapy followed by radiation, which is insufficient to cure stage four cancers[3]. Salmonella enteric has long been shown to have inherent tumor targeting properties and have been able to penetrate and exist in all aspects of the tumor environment, something that chemotherapy is unable to achieve. This lab has developed a genetically modified Salmonella typhimurium (GMS) which is able to deliver DNA vaccines or synthesized proteins directly to tumor sites. These GMS strains have been used to deliver human TNF-related apoptosis inducing ligand (TRAIL) protein directly to tumor sites, but expression level was limited. It is the hope of the experiment that codon optimization of TRAIL to S. typhimurium preferred codons will lead to increased TRAIL expression in the GMS. For preliminary studies, BALB/c mice were subcutaneously challenged with CT-26 murine colorectal cancer cells and treated with an intra-tumor injection with either PBS, strain GMS + PCMV FasL (P2), or strain GMS + Pmus FasL). APC/CDX2 mutant mice were also induced to develop human colon polyps and treated with either PBS, strain GMS + vector (P1), P2, or P3. The BALB/c mouse showed statistically significant levels of decreased tumor size in groups treated with P2 or P3. The APC/CDX2 mouse study showed statistically significant levels of decreased colon polyp numbers in groups treated with P3, as expected, but was not significantly significant for groups treated with P1 and P2. In addition, TRAIL was codon optimized for robust synthesis in Salmonella. The construct will be characterized and evaluated in vitro and in vivo. Hopefully, the therapeutic effect of codon optimized TRAIL will be maximal while almost completely minimizing any unintended side effects.
ContributorsCrawford, Courtney Rose (Co-author) / Crawford, Courtney (Co-author) / Kong, Wei (Thesis director) / Shi, Yixin (Committee member) / Fu, Lingchen (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This thesis examines Care Not Cash, a welfare reform measure that replaced traditional cash General Assistance program payments for homeless persons in San Francisco with in-kind social services. Unlike most welfare reform measures, proponents framed Care Not Cash as a progressive policy, aimed at expanding social services and government care for this vulnerable population. Drawing on primary and secondary documents, as well as interviews with homelessness policy experts, this thesis examines the historical and political success of Care Not Cash, and explores the potential need for implementation of a similar program in Phoenix, Arizona.
ContributorsMcCutcheon, Zachary Ryan (Author) / Lucio, Joanna (Thesis director) / Williams, David (Committee member) / Bretts-Jamison, Jake (Committee member) / School of Public Affairs (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Many pathogens are bacteria and antibiotic resistance is increasing. The development of novel treatments is hampered by a poor understanding of the mechanisms of their regulation. Specifically, non-coding RNAs play an important role in the internal regulation of bacteria. To further the investigation of non-coding RNA and pathogenicity, RNA sequencing data for PorX/PorY dependent regulation in P. gingivalis, a Gram negative oral pathogen was studied. The PorX/PorY two component regulatory system controls phenotypes for this bacteria's virulence including an important type IX secretion system for gingipain proteases, which degrades host cytokines, down regulating the host response by reducing inflammation. This study compared transcription of non-coding RNA in wild type and PorX knockout mutant strain, in the 33277 strain and the more virulent W83 strain in both liquid and solid cultures to identify and categorize loci of genomic sequence for further study of porX/porY regulation.
ContributorsHoenack, Michael Anthony (Author) / Kong, Wei (Thesis director) / Shi, Yixin (Committee member) / Lingchen, Fu (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Cancer treatments such as chemotherapy and radiation are expensive, painful, and often ineffective, as they compromise the patient’s immune system. Genetically-modified Salmonella Typhimurium (GMS) strains, however, have been proven to target tumors and suppress tumor growth. The GMS then undergo programmed lysis, optimally leaving no trace of Salmonella in the body. Additionally, constant culturing of S. Typhimurium changes the pH of the culture medium. The objective of this research is to investigate using Salmonella to induce changes in the typically acidic tumor microenvironment (TME) pH, ideally hindering tumor growth. Future studies involve utilizing Salmonella to treat a multitude of cancers.
ContributorsFleck, Kiera (Author) / Kong, Wei (Thesis director) / Fu, Lingchen (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05
Description
Modified Salmonella strains and recombinant DNA in a plasmid are used to construct a
Salmonella strain that is dependent on the experimentally inserted plasmid. This construction
will be done via lab techniques such as polymerase chain reactions (PCR), transformation, and other means to create this construction. With future successful construction, the inhibition of flagella assembly, within the tumor environment, and increased synthesis of flagellin will be
possible. In the case that only assembly is prevented, then, the reliance on the lysis system to
release flagellin into the tumor microenvironment will be used as a means to induce immune
response. With the success of the self-lysis ability, these strains could be used to target these
tumor cells to deliver anticancer material as a vaccine delivery system.
ContributorsShagi, Agnel (Author) / Kong, Wei (Thesis director) / Fu, Lingchen (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
ABSTRACTWith the National Aeronautics and Space Administration (NASA) Psyche Mission, humans will soon have the first opportunity to explore a new kind of planetary body: one composed mostly of metal as opposed to stony minerals or ices. Identifying the composition of asteroids from Earth-based observations has been an ongoing challenge. Although optical reflectance spectra, radar, and orbital dynamics can constrain an asteroid’s mineralogy and bulk density, in many cases there is not a clear or precise match with analogous materials such as meteorites. Additionally, the surfaces of asteroids and other small, airless planetary bodies can be heavily modified over geologic time by exposure to the space environment. To accurately interpret remote sensing observations of metal-rich asteroids, it is therefore necessary to understand how the processes active on asteroid surfaces affect metallic materials. This dissertation represents a first step toward that understanding. In collaboration with many colleagues, I have performed laboratory experiments on iron meteorites to simulate solar wind ion irradiation, surface heating, micrometeoroid bombardment, and high-velocity impacts. Characterizing the meteorite surface’s physical and chemical properties before and after each experiment can constrain the effects of each process on a metal-rich surface in space. While additional work will be needed for a complete understanding, it is nevertheless possible to make some early predictions of what (16) Psyche’s surface regolith might look like when humans observe it up close. Moreover, the results of these experiments will inform future exploration beyond asteroid Psyche as humans attempt to understand how Earth’s celestial neighborhood came to be.
ContributorsChristoph, John Morgan M. (Author) / Elkins-Tanton, Linda (Thesis advisor) / Williams, David (Committee member) / Dukes, Catherine (Committee member) / Sharp, Thomas (Committee member) / Bell III, James (Committee member) / Arizona State University (Publisher)
Created2023