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- All Subjects: Business Administration
- Genre: Academic theses
- Creators: Arizona State University
- Status: Published
Description
Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian model organism for comparative studies between the vertebrates and for studies of biological processes unique to reptiles. To help fill in this gap the green anole lizard, Anolis carolinensis, is being adapted as a model organism. Despite the recent release of the complete genomic sequence of the A. carolinensis, the lizard lacks some resources to aid researchers in their studies. Particularly, the lack of transcriptomic resources for lizard has made it difficult to identify genes complete with alternative splice forms and untranslated regions (UTRs). As part of this work the genome annotation for A. carolinensis was improved through next generation sequencing and assembly of the transcriptomes from 14 different adult and embryonic tissues. This revised annotation of the lizard will improve comparative studies between vertebrates, as well as studies within A. carolinensis itself, by providing more accurate gene models, which provide the bases for molecular studies. To demonstrate the utility of the improved annotations and reptilian model organism, the developmental process of somitogenesis in the lizard was analyzed and compared with other vertebrates. This study identified several key features both divergent and convergent between the vertebrates, which was not previously known before analysis of a reptilian model organism. The improved genome annotations have also allowed for molecular studies of tail regeneration in the lizard. With the annotation of 3' UTR sequences and next generation sequencing, it is now possible to do expressional studies of miRNA and predict their mRNA target transcripts at genomic scale. Through next generation small RNA sequencing and subsequent analysis, several differentially expressed miRNAs were identified in the regenerating tail, suggesting miRNA may play a key role in regulating this process in lizards. Through miRNA target prediction several key biological pathways were identified as potentially under the regulation of miRNAs during tail regeneration. In total, this work has both helped advance A. carolinensis as model system and displayed the utility of a reptilian model system.
ContributorsEckalbar, Walter L (Author) / Kusumi, Kenro (Thesis advisor) / Huentelman, Matthew (Committee member) / Rawls, Jeffery (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2012
Description
The processes of a human somatic cell are very complex with various genetic mechanisms governing its fate. Such cells undergo various genetic mutations, which translate to the genetic aberrations that we see in cancer. There are more than 100 types of cancer, each having many more subtypes with aberrations being unique to each. In the past two decades, the widespread application of high-throughput genomic technologies, such as micro-arrays and next-generation sequencing, has led to the revelation of many such aberrations. Known types and subtypes can be readily identified using gene-expression profiling and more importantly, high-throughput genomic datasets have helped identify novel sub-types with distinct signatures. Recent studies showing usage of gene-expression profiling in clinical decision making in breast cancer patients underscore the utility of high-throughput datasets. Beyond prognosis, understanding the underlying cellular processes is essential for effective cancer treatment. Various high-throughput techniques are now available to look at a particular aspect of a genetic mechanism in cancer tissue. To look at these mechanisms individually is akin to looking at a broken watch; taking apart each of its parts, looking at them individually and finally making a list of all the faulty ones. Integrative approaches are needed to transform one-dimensional cancer signatures into multi-dimensional interaction and regulatory networks, consequently bettering our understanding of cellular processes in cancer. Here, I attempt to (i) address ways to effectively identify high quality variants when multiple assays on the same sample samples are available through two novel tools, snpSniffer and NGSPE; (ii) glean new biological insight into multiple myeloma through two novel integrative analysis approaches making use of disparate high-throughput datasets. While these methods focus on multiple myeloma datasets, the informatics approaches are applicable to all cancer datasets and will thus help advance cancer genomics.
ContributorsYellapantula, Venkata (Author) / Dinu, Valentin (Thesis advisor) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Keats, Jonathan (Committee member) / Arizona State University (Publisher)
Created2014
Description
The technology expansion seen in the last decade for genomics research has permitted the generation of large-scale data sources pertaining to molecular biological assays, genomics, proteomics, transcriptomics and other modern omics catalogs. New methods to analyze, integrate and visualize these data types are essential to unveil relevant disease mechanisms. Towards these objectives, this research focuses on data integration within two scenarios: (1) transcriptomic, proteomic and functional information and (2) real-time sensor-based measurements motivated by single-cell technology. To assess relationships between protein abundance, transcriptomic and functional data, a nonlinear model was explored at static and temporal levels. The successful integration of these heterogeneous data sources through the stochastic gradient boosted tree approach and its improved predictability are some highlights of this work. Through the development of an innovative validation subroutine based on a permutation approach and the use of external information (i.e., operons), lack of a priori knowledge for undetected proteins was overcome. The integrative methodologies allowed for the identification of undetected proteins for Desulfovibrio vulgaris and Shewanella oneidensis for further biological exploration in laboratories towards finding functional relationships. In an effort to better understand diseases such as cancer at different developmental stages, the Microscale Life Science Center headquartered at the Arizona State University is pursuing single-cell studies by developing novel technologies. This research arranged and applied a statistical framework that tackled the following challenges: random noise, heterogeneous dynamic systems with multiple states, and understanding cell behavior within and across different Barrett's esophageal epithelial cell lines using oxygen consumption curves. These curves were characterized with good empirical fit using nonlinear models with simple structures which allowed extraction of a large number of features. Application of a supervised classification model to these features and the integration of experimental factors allowed for identification of subtle patterns among different cell types visualized through multidimensional scaling. Motivated by the challenges of analyzing real-time measurements, we further explored a unique two-dimensional representation of multiple time series using a wavelet approach which showcased promising results towards less complex approximations. Also, the benefits of external information were explored to improve the image representation.
ContributorsTorres Garcia, Wandaliz (Author) / Meldrum, Deirdre R. (Thesis advisor) / Runger, George C. (Thesis advisor) / Gel, Esma S. (Committee member) / Li, Jing (Committee member) / Zhang, Weiwen (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation offers three essays that investigate consumers’ health-related food choices and behaviors from three different, yet complementary, angles. The first essay uses an eye-tracking experiment to examine consumers’ visual attention to the Nutrition Facts Panels for healthy and unhealthy products. In this essay, I focus on how involvement and familiarity affect consumers’ attention toward the Nutrition Facts panel and how these two psychological factors interact with new label format changes in attracting consumers’ attention. In the second essay, I demonstrate using individual-level scanner data that nutritional attributes interact with marketing mix elements to affect consumers’ nutrition intake profiles and their intra-category substitution patterns. My findings suggest that marketing-mix sensitivities are correlated with consumers’ preferences for nutrient attributes in ways that depend on the “healthiness” of the nutrient. For instance, featuring promotes is positively correlated with “healthy” nutritional characteristics such as high-protein, low-fat, or low-carbohydrates, whereas promotion and display are positively correlated with preferences for “unhealthy” characteristics such as high-fat, or high-carbohydrates. I use model simulations to show that some marketing-mix elements are able to induce consumers to purchase items with higher maximum-content levels than others. The fourth chapter shows that dieters are not all the same. I develop and validate a new scale that measures lay theories about abstinence vs. moderation. My findings from a series of experiments indicate that dieters’ recovery from recalled vs. actual indulgences depend on whether they favor abstinence or moderation. However, compensatory coping strategies provide paths for people with both lay theories to recover after an indulgence, in their own ways. The three essays provide insights into individual differences that determine approaches of purchase behaviors, and consumption patterns, and life style that people choose, and these insights have potential policy implications to aid in designing the food-related interventions and policies to improve the healthiness of consumers’ consumption profiles and more general food well-being.
ContributorsXie, Yi (Author) / Richards, Timothy (Thesis advisor) / Mandel, Naomi (Committee member) / Grebitus, Carola (Committee member) / Arizona State University (Publisher)
Created2018
Description
This article can be divided into six parts.
The first chapter analyzes the background, theatrical and particle reasons of this research. The author argues that the management of law firm needs a set of good system. The first one is operating the law firm in scale, and the other on is corporate management model, which shall be constructed in detail in the paper and will be put into practice by the law firm in which the author is worked.
The second chapter will introduce modern management theory, combining the situation of management in our law firm to analyze, raising some reasonable suggestions and instructions to promote our law firm to achieve the corporate management.
In the third chapter, the first chapter, starting with the review of the development process of foreign and our law firms, listing the organizational forms and the characteristics of our law firm, analyzing the situation and the drawbacks of the law firm management.
The fourth and fifth chapter introduce he background, the connotation of the corporate management model, listing the development and successful experience of some typical cases in respect of corporate management.
In the last chapter, the construction of corporate management model will be introduced in terms of organization form, human resource management and informationizing development.
The corporate management model is not mature in china. Though it is not easy to reform the existing model, but it should be believed that the development benefiting the legal industry will be achieved.
The first chapter analyzes the background, theatrical and particle reasons of this research. The author argues that the management of law firm needs a set of good system. The first one is operating the law firm in scale, and the other on is corporate management model, which shall be constructed in detail in the paper and will be put into practice by the law firm in which the author is worked.
The second chapter will introduce modern management theory, combining the situation of management in our law firm to analyze, raising some reasonable suggestions and instructions to promote our law firm to achieve the corporate management.
In the third chapter, the first chapter, starting with the review of the development process of foreign and our law firms, listing the organizational forms and the characteristics of our law firm, analyzing the situation and the drawbacks of the law firm management.
The fourth and fifth chapter introduce he background, the connotation of the corporate management model, listing the development and successful experience of some typical cases in respect of corporate management.
In the last chapter, the construction of corporate management model will be introduced in terms of organization form, human resource management and informationizing development.
The corporate management model is not mature in china. Though it is not easy to reform the existing model, but it should be believed that the development benefiting the legal industry will be achieved.
ContributorsZhu, Ping (Author) / Gu, Bin (Thesis advisor) / Chang, Chun (Thesis advisor) / Zhu, Ning (Committee member) / Arizona State University (Publisher)
Created2017
Description
Recombinases are powerful tools for genome engineering and synthetic biology, however recombinases are limited by a lack of user-programmability and often require complex directed-evolution experiments to retarget specificity. Conversely, CRISPR systems have extreme versatility yet can induce off-target mutations and karyotypic destabilization. To address these constraints we developed an RNA-guided recombinase protein by fusing a hyperactive mutant resolvase from transposon TN3 to catalytically inactive Cas9. We validated recombinase-Cas9 (rCas9) function in model eukaryote Saccharomyces cerevisiae using a chromosomally integrated fluorescent reporter. Moreover, we demonstrated cooperative targeting by CRISPR RNAs at spacings of 22 or 40bps is necessary for directing recombination. Using PCR and Sanger sequencing, we confirmed rCas9 targets DNA recombination. With further development we envision rCas9 becoming useful in the development of RNA-programmed genetic circuitry as well as high-specificity genome engineering.
ContributorsStandage-Beier, Kylie S (Author) / Wang, Xiao (Thesis advisor) / Brafman, David A (Committee member) / Tian, Xiao-jun (Committee member) / Arizona State University (Publisher)
Created2018
Description
Due to the booming young mothers and fathers in the new era as well as the changes in the concept of parenting and the favorable liberalization of China's second child policy, the maternal-baby nursing market continues to grow, and it has become a must for businesses nowadays. In 2020, the size of the maternal-baby nursing market will reach 3.6 trillion. (Data: Yibang Power China's Maternal and Child Industry White Paper 2017).
The rapid development of mobile Internet, highly transparent information, consumers grasp the sovereignty, along with the rise of the middle class, consumption increase encouraged personalized, customized needs. The boundaries between online and offline are becoming increasingly blurred. Consumers are more inclined to choose multi-category with service channel providers. If the retailers still rely on good market resources, and the difference between the sales and purchase of commodities, they will face a huge challenge of the decrease in passenger flow and a decline in performance.
The paper takes the relationship between maternal-baby nursing retailers and targets customers as the study object, based on customer service of maternal-baby nursing retailer data, empirical studies, we found that this particular group, mothers and babies, especially value safety, quality, public praise and community review. If the retail enterprise attaches importance to establishing relationships with customers and enhances the relational viscosity through mutual trust, emotional formation and spread of public praise, it will help to increase the traffic volume and increase the output value of single customers.
The maternal-baby nursing retailers form a strong relationship between enterprises and customers by establishing a strong relationship between products and customers, employees and customers, and customers to customers. Maternal-baby nursing retailers operate single-customer value deeply, build a heavy membership system and manage customer assets, thereby enhancing their brand and performance.
The research on the method of establishing the strong tie can be considered as an analysis of feasibility. The research results of this paper will help to improve the overall customer service experience and satisfaction of the mother and infant retail industry, enhance the development of the whole industry and draw significance lessons from other service industries.
The rapid development of mobile Internet, highly transparent information, consumers grasp the sovereignty, along with the rise of the middle class, consumption increase encouraged personalized, customized needs. The boundaries between online and offline are becoming increasingly blurred. Consumers are more inclined to choose multi-category with service channel providers. If the retailers still rely on good market resources, and the difference between the sales and purchase of commodities, they will face a huge challenge of the decrease in passenger flow and a decline in performance.
The paper takes the relationship between maternal-baby nursing retailers and targets customers as the study object, based on customer service of maternal-baby nursing retailer data, empirical studies, we found that this particular group, mothers and babies, especially value safety, quality, public praise and community review. If the retail enterprise attaches importance to establishing relationships with customers and enhances the relational viscosity through mutual trust, emotional formation and spread of public praise, it will help to increase the traffic volume and increase the output value of single customers.
The maternal-baby nursing retailers form a strong relationship between enterprises and customers by establishing a strong relationship between products and customers, employees and customers, and customers to customers. Maternal-baby nursing retailers operate single-customer value deeply, build a heavy membership system and manage customer assets, thereby enhancing their brand and performance.
The research on the method of establishing the strong tie can be considered as an analysis of feasibility. The research results of this paper will help to improve the overall customer service experience and satisfaction of the mother and infant retail industry, enhance the development of the whole industry and draw significance lessons from other service industries.
ContributorsWang, Jianguo (Author) / Gu, Bin (Thesis advisor) / Chen, Hong (Thesis advisor) / Cui, Haitao (Committee member) / Arizona State University (Publisher)
Created2018
Description
This study examines the 3 key questions of media budget allocation, to find our a better invest model. Including spending share of traditional media and digital media, program selection strategy and duration mix optimization to analyse the trend of sample A (a global cosmetic brand) . Based on every test media campaign, we do research of media performance and sales volumn, add youth consumer behavior result, to develop a media investment ROI model for this brand. Create the evaluation system according to past big data and find the learnings of different length TVC usage. Of course all relavant findings and implications will be summarized after every section.
ContributorsXu, Jin (Author) / Gu, Bin (Thesis advisor) / Chen, Xinlei (Thesis advisor) / Shao, Benjamin (Committee member) / Arizona State University (Publisher)
Created2018
Description
Cancer is a heterogeneous disease with discrete oncogenic mechanisms. P53 mutation is the most common oncogenic mutation in many cancers including breast cancer. This dissertation focuses on fundamental genetic alterations enforced by p53 mutation as an indirect target. p53 mutation upregulates the mevalonate pathway genes altering cholesterol biosynthesis and prenylation. Prenylation, a lipid modification, is required for small GTPases signaling cascades. Project 1 demonstrates that prenylation inhibition can specifically target cells harboring p53 mutation resulting in reduced tumor proliferation and migration. Mutating p53 is associated with Ras and RhoA activation and statin prevents this activity by inhibiting prenylation. Ras-related pathway genes were selected from the transcriptomic analysis for evaluating correlation to statin sensitivity. A gene signature of seventeen genes and TP53 genotype (referred to as MPR signature) is generated to predict response to statins. MPR signature is validated through two datasets of drug screening in cell lines. As advancements in targeted gene modification are rising, the CRISPR-Cas9 technology has emerged as a new cancer therapeutic strategy. One of the important risk factors in gene therapy is the immune recognition of the exogenous therapeutic tool, resulting in obstruction of treatment and possibly serious health consequences. Project 2 describes a method development that can potentially improve the safety and efficacy of gene-targeting proteins. A cohort of 155 healthy individuals was screened for pre-existing B cell and T cell immune response to the S. pyogenes Cas9 protein. We detected antibodies against Cas9 in more than 10% of the healthy population and identified two immunodominant T cell epitopes of this protein. A de-immunized Cas9 that maintains the wild-type functionality was engineered by mutating the identified T cell epitopes. The gene signature and method described here have the potential to improve strategies for genome-driven tumor targeting.
ContributorsRoshdi Ferdosi, Shayesteh (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Thesis advisor) / Woodbury, Neel (Committee member) / Borges, Chad (Committee member) / Arizona State University (Publisher)
Created2017