Matching Items (43,913)
Description
Gene therapy is a promising technology for the treatment of various nonheritable and genetically acquired diseases. It involves delivery of a therapeutic gene into target cells to induce cellular responses against diseases. Successful gene therapy requires an efficient gene delivery vector to deliver genetic materials into target cells. There are two major classes of gene delivery vectors: viral and non-viral vectors. Recently, non-viral vectors such as cationic polymers have attracted more attention than viral vectors because they are versatile and non-immunogenic. However, cationic polymers suffer from poor gene delivery efficiency due to biological barriers. The objective of this research is to develop strategies to overcome the barriers and enhance polymer-mediated transgene expression. This study aimed to (i) develop new polymer vectors for gene delivery, (ii) investigate the intracellular barriers in polymer-mediated gene delivery, and (iii) explore new approaches to overcome the barriers. A cationic polymer library was developed by employing a parallel synthesis and high-throughput screening method. Lead polymers from the library were identified from the library based on relative levels of transgene expression and toxicity in PC3-PSMA prostate cancer cells. However, transgene expression levels were found to depend on intracellular localization of polymer-gene complexes (polyplexes). Transgene expression was higher when polyplexes were dispersed rather than localized in the cytoplasm. Combination treatments using small molecule chemotherapeutic drugs, e.g. histone deacetylase inhibitors (HDACi) or Aurora kinase inhibitor (AKI) increased dispersion of polyplexes in the cytoplasm and significantly enhanced transgene expression. The combination treatment using polymer-mediated delivery of p53 tumor-suppressor gene and AKI increased p53 expression in PC3-PSMA cells, inhibited the cell proliferation by ~80% and induced apoptosis. Polymer-mediated p53 gene delivery in combination with AKI offers a promising treatment strategy for in vivo and clinical studies of cancer gene therapy.
ContributorsBarua, Sutapa (Author) / Rege, Kaushal (Thesis advisor) / Dai, Lenore (Committee member) / Meldrum, Deirdre R. (Committee member) / Sierks, Michael (Committee member) / Voelkel-Johnson, Christina (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation studies routing in small-world networks such as grids plus long-range edges and real networks. Kleinberg showed that geography-based greedy routing in a grid-based network takes an expected number of steps polylogarithmic in the network size, thus justifying empirical efficiency observed beginning with Milgram. A counterpart for the grid-based model is provided; it creates all edges deterministically and shows an asymptotically matching upper bound on the route length. The main goal is to improve greedy routing through a decentralized machine learning process. Two considered methods are based on weighted majority and an algorithm of de Farias and Megiddo, both learning from feedback using ensembles of experts. Tests are run on both artificial and real networks, with decentralized spectral graph embedding supplying geometric information for real networks where it is not intrinsically available. An important measure analyzed in this work is overpayment, the difference between the cost of the method and that of the shortest path. Adaptive routing overtakes greedy after about a hundred or fewer searches per node, consistently across different network sizes and types. Learning stabilizes, typically at overpayment of a third to a half of that by greedy. The problem is made more difficult by eliminating the knowledge of neighbors' locations or by introducing uncooperative nodes. Even under these conditions, the learned routes are usually better than the greedy routes. The second part of the dissertation is related to the community structure of unannotated networks. A modularity-based algorithm of Newman is extended to work with overlapping communities (including considerably overlapping communities), where each node locally makes decisions to which potential communities it belongs. To measure quality of a cover of overlapping communities, a notion of a node contribution to modularity is introduced, and subsequently the notion of modularity is extended from partitions to covers. The final part considers a problem of network anonymization, mostly by the means of edge deletion. The point of interest is utility preservation. It is shown that a concentration on the preservation of routing abilities might damage the preservation of community structure, and vice versa.
ContributorsBakun, Oleg (Author) / Konjevod, Goran (Thesis advisor) / Richa, Andrea (Thesis advisor) / Syrotiuk, Violet R. (Committee member) / Czygrinow, Andrzej (Committee member) / Arizona State University (Publisher)
Created2011
Description
The failure to withhold inappropriate behavior is a central component of most impulse control disorders, including Attention Deficit Hyperactivity Disorder (ADHD). The present study examined the effects of housing environment and methylphenidate (a drug often prescribed for ADHD) on the performance of rats in two response inhibition tasks: differential reinforcement of low rate (DRL) and fixed minimum interval (FMI). Both tasks required rats to wait a fixed amount of time (6 s) before emitting a reinforced response. The capacity to withhold the target response (volitional inhibition) and timing precision were estimated on the basis of performance in each of the tasks. Paradoxically, rats housed in a mildly enriched environment that included a conspecific displayed less volitional inhibition in both tasks compared to rats housed in an isolated environment. Enriched housing, however, increased timing precision. Acute administration of methylphenidate partially reversed the effects of enriched housing. Implications of these results in the assessment and treatment of ADHD-related impulsivity are discussed.
ContributorsHill, Jade C (Author) / Sanabria, Federico (Thesis advisor) / Killeen, Peter (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2011
Description
Geography, and the social sciences more broadly, have long operated within what is arguably a paradigm of the visual. Expanding the reach of geographical consideration into the realm of the aural, though in no way leaving behind the visual, opens the discipline to new areas of human and cultural geography invisible in ocular-centric approaches. At its broadest level, my argument in this dissertation is that music can no longer be simply an object of geographical research. Re-conceptualized and re-theorized in a geographical context to take into account its very real, active, and more-than-representational presence in social life, music provides actual routes to geographic knowledge of the world. I start by constructing a theoretical framework and methodological approach for studying music beyond representation. Based on these theoretical and methodological arguments, I present four narratives that unfold at the intersections of race and music in the northeast Brazilian city of Salvador. From the favelas of Rio de Janeiro to the troubled neighborhood of the Pelourinho, from the manic tempos of samba to the laid back grooves of samba-reggae, and in the year-round competition between the oppressive forces of ordinary time and the fleeting possibility of carnival, music emerges as a creative societal force with affects and effects far beyond the realm of representation. Together, these narratives exemplify the importance of expanding geographical considerations beyond a strictly visual framework. These narratives contribute to the musicalization of the discipline of geography.
ContributorsFinn, John C (Author) / McHugh, Kevin (Thesis advisor) / Lukinbeal, Christopher (Committee member) / Bolin, Bob (Committee member) / Price, Patricia (Committee member) / Arizona State University (Publisher)
Created2011
Description
Lead is a neurotoxin that has been shown to have a long and lasting impact on the brains, bodies, and behaviors of those who are poisoned. It also has a greater presence in communities with high levels of poverty and minority populations. Compounded over time, the effects of lead poisoning, even at low levels of exposure, impact a child's readiness and ability to learn. To investigate the relationship between the risk of lead poisoning, school level academic achievement, and community demographics, three sets of data were combined. The Lead Poisoning Risk Index (LPRI), used to quantify the risk in each census tract of being poisoned by lead, standardized state assessment data for third grade reading and eighth grade math, and census 2000 demographic data were combined to provide information for all Arizona schools and census tracts. When achievement was analyzed at the school level using descriptive, bivariate correlation, and multivariate regression analyses, lead's impact practically disappeared, exposing the powerful effect of poverty and race on achievement. At a school in Arizona, the higher the percentage of students who are poor or Hispanic, African American or Native American, these analyses' predictive models suggest there will be a greater percentage of students who fail the third grade AIMS reading and eighth grade AIMS math tests. If better achievement results are to be realized, work must be done to mitigate the effects of poverty on the lives of students. In order to improve schools, there needs to be an accounting for the context within which schools operate and a focus on improving the neighborhoods and the quality of life for the families of students.
ContributorsGehrman, Matthew Paul (Author) / Berliner, David C. (Thesis advisor) / Garcia, David (Committee member) / Danzig, Arnold (Committee member) / Arizona State University (Publisher)
Created2011
Description
Although the issue of factorial invariance has received increasing attention in the literature, the focus is typically on differences in factor structure across groups that are directly observed, such as those denoted by sex or ethnicity. While establishing factorial invariance across observed groups is a requisite step in making meaningful cross-group comparisons, failure to attend to possible sources of latent class heterogeneity in the form of class-based differences in factor structure has the potential to compromise conclusions with respect to observed groups and may result in misguided attempts at instrument development and theory refinement. The present studies examined the sensitivity of two widely used confirmatory factor analytic model fit indices, the chi-square test of model fit and RMSEA, to latent class differences in factor structure. Two primary questions were addressed. The first of these concerned the impact of latent class differences in factor loadings with respect to model fit in a single sample reflecting a mixture of classes. The second question concerned the impact of latent class differences in configural structure on tests of factorial invariance across observed groups. The results suggest that both indices are highly insensitive to class-based differences in factor loadings. Across sample size conditions, models with medium (0.2) sized loading differences were rejected by the chi-square test of model fit at rates just slightly higher than the nominal .05 rate of rejection that would be expected under a true null hypothesis. While rates of rejection increased somewhat when the magnitude of loading difference increased, even the largest sample size with equal class representation and the most extreme violations of loading invariance only had rejection rates of approximately 60%. RMSEA was also insensitive to class-based differences in factor loadings, with mean values across conditions suggesting a degree of fit that would generally be regarded as exceptionally good in practice. In contrast, both indices were sensitive to class-based differences in configural structure in the context of a multiple group analysis in which each observed group was a mixture of classes. However, preliminary evidence suggests that this sensitivity may contingent on the form of the cross-group model misspecification.
ContributorsBlackwell, Kimberly Carol (Author) / Millsap, Roger E (Thesis advisor) / Aiken, Leona S. (Committee member) / Enders, Craig K. (Committee member) / Mackinnon, David P (Committee member) / Arizona State University (Publisher)
Created2011
Description
Templates are wildly used in Web sites development. Finding the template for a given set of Web pages could be very important and useful for many applications like Web page classification and monitoring content and structure changes of Web pages. In this thesis, two novel sequence-based Web page template detection algorithms are presented. Different from tree mapping algorithms which are based on tree edit distance, sequence-based template detection algorithms operate on the Prüfer/Consolidated Prüfer sequences of trees. Since there are one-to-one correspondences between Prüfer/Consolidated Prüfer sequences and trees, sequence-based template detection algorithms identify the template by finding a common subsequence between to Prüfer/Consolidated Prüfer sequences. This subsequence should be a sequential representation of a common subtree of input trees. Experiments on real-world web pages showed that our approaches detect templates effectively and efficiently.
ContributorsHuang, Wei (Author) / Candan, Kasim Selcuk (Thesis advisor) / Sundaram, Hari (Committee member) / Davulcu, Hasan (Committee member) / Arizona State University (Publisher)
Created2011
Description
Early childhood is a special and amazing period in a child's development. It is a period during which all facets of a human being-cognitive, linguistic, physical, emotional, social, and spiritual--are rapidly developing and influenced by a child's interactions with her socializers and environment. Fundamentally, what happens during this critical period will influence and impact a child's future learning. Much of what is known about children's development comes from research focusing primarily on mainstream English speaking children. However, not much that is known about Indigenous children and their early period of child development. Therefore, this thesis research focused on Diné children and their early childhood experiences that occur during the fundamental time period before Diné children enter preschool. It also examines the contemporary challenges that Diné parents and other cultural caretakers face in ensuring that Diné infants and young children are taught those important core elements that make them uniquely Diné. The research questions that guide this thesis are: 1.What do Diné people believe about children and their abilities? 2.What do Diné children need to learn in order to become Diné? 3. What are the Diné childhood rearing beliefs and practices? 4. Why aren't Diné parents and grandparents teaching their children how to be Diné? Findings reveal an early childhood experience in which children are viewed as true explorers and highly intelligent, inquisitive learners and included as integral participants and contributors to the family and community. This thesis concludes with a discussion of the multidimensional transitions, such as the shift from the Diné language to English in Diné homes and communities that have occurred in the Diné way of life and how they have impacted how Diné children are socialized. Creative alternatives for increasing Diné childhood speakers on and off the Navajo reservation are also considered.
ContributorsBia, Sunshine Sallie (Author) / Romero-Little, Mary E (Thesis advisor) / Tippeconnic, John (Thesis advisor) / Martinez, David (Committee member) / Arizona State University (Publisher)
Created2011
Description
ABSTRACT As a writer and a journalist, I have always been interested in narrative. When I moved to the small town of Wickenburg, Arizona in 2003, and began to get acquainted, a friend said to me, "The only way you leave Wickenburg is in a box." The town of Wickenburg places much importance on its history, a focus that led me to explore its related literature of the U.S. West, moving from there to think about evocative objects, collections, and to Material Culture Theory. This thesis considers three objects as springboards for exploring identity, sense of place, memory, and the narrative threads that bring these together. Two of these objects are specific to local history. The first is one of the leather badges worn by the women of Las Damas, a Wickenburg horse riding association. The second is a bronze sculpture, "Fatal Dismount," created by local rancher Mary Cooper Hamill, in which the artist depicts a moment, highly significant to her family, that also speaks to and from local history. The third object is a gold bead heirloom necklace that was handed down to me, the fifth-generation recipient. I conclude with a discussion of how evocative objects, handed down across generations, shape two memoirs by Isabel Allende, Paula, and My Invented Country. In the case of each object, the study of material culture provides a framework for understanding how women have created spaces for themselves, both now and in the past by interacting with objects, articulating identities, making meaning and re-creating history through memories and storytelling.
ContributorsNeu, Lora (Author) / Horan, Elizabeth R (Thesis advisor) / Tobin, Mary E (Committee member) / Morris, Paul (Committee member) / Arizona State University (Publisher)
Created2011
Description
Meteorology is an uncommon term rarely resonating through elementary classrooms. However, it is a concept found in both fourth and sixth grade Arizona science standards. As issues involving the environment are becoming more pertinent, it is important to study and understand atmospheric processes along with fulfilling the standards for each grade level. This thesis project teaches the practical skills of weather map reading and weather forecasting through the creation and execution of an after school lesson with the aide of seven teen assistants.
ContributorsChoulet, Shayna (Author) / Walters, Debra (Thesis director) / Oliver, Jill (Committee member) / Balling, Robert (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12