Matching Items (13)
Filtering by
- Genre: Masters Thesis
Description
Recombinant protein expression is essential to biotechnology and molecular medicine, but facile methods for obtaining significant quantities of folded and functional protein in mammalian cell culture have been lacking. Here I describe a novel 37-nucleotide in vitro selected sequence that promotes unusually high transgene expression in a vaccinia driven cytoplasmic expression system. Vectors carrying this sequence in a monocistronic reporter plasmid produce >1,000-fold more protein than equivalent vectors with conventional vaccinia promoters. Initial mechanistic studies indicate that high protein expression results from dual activity that impacts both transcription and translation. I suggest that this motif represents a powerful new tool in vaccinia-based protein expression and vaccine development technology.
ContributorsFlores, Julia Anne (Author) / Chaput, John C (Thesis advisor) / Jacobs, Bertram (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2012
Description
The TP53 tumor suppressor gene is the most frequently mutated gene in human cancers. In the highly aggressive triple negative breast cancer (TNBC), TP53 is mutated in 80% of cases. TNBC lacks viable drug targets, resulting in a low prognosis (12.2% 5 year survivability rate). As such, the discovery of druggable targets in TNBC would be beneficial. Mutated p53 protein typically occurs as a missense mutation and often endows cancer cells with gain of function (GOF) properties by dysregulating metabolic pathways. One of these frequently dysregulated pathways is the Hippo/Yes-associated protein-1 (YAP1)/WW Domain Containing Transcription Regulator 1 (TAZ) tumor suppressor pathway. This study therefore analyzed the involvement of the Hippo/YAP1/TAZ pathway in p53-mediated breast cancer cell invasion. From an RNA-seq screen in MCF10A cell lines harboring different TP53 missense mutations, each with a differing invasive phenotype, components of the Hippo pathway were found to correlate with cell invasion. To this end, the active and inactive forms of YAP1 and TAZ were studied. Phosphorylated (inactive) YAP1 and TAZ are retained in the cytoplasm and eventually degraded. Unphosphorylated (active) YAP1 and TAZ translocate to the nucleus to activate TEAD-family transcription factors, inducing cell survival and proliferation genes leading to increased cell invasion. Using quantitative western blot analysis, it was found that inactive TAZ expression was lower in the most invasive cell lines and higher in the least invasive cell lines (p = 0.003). Moreover, the ratio of inactive TAZ protein to total TAZ protein was also shown to be predominantly lower in the invasive cell lines compared to the non-invasive lines (p = 0.04). Finally, active TAZ expression was primarily higher in p53-mutant invasive cell lines and lower in non-invasive p53 mutant cells. Additionally, although YAP1 and TAZ are thought to be functionally redundant, the pattern seen in TAZ was not seen in the YAP1 protein. Taken together, the results demonstrated here suggest that TAZ holds a more dominant role in governing TNBC cell invasion compared to YAP1 and further highlights TAZ as a potential therapeutic target in TNBC.
ContributorsGrief, Dustin (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Although Saudi Arabia is moving towards a sustainable future, Existing residential buildings in the country are extremely unsustainable. Therefore, there is a necessity for greening the existing residential building. Mostadam green rating systems was developed by the Saudi ministry of housing in 2019 to address the long-term sustainability vision in residential buildings in the country. By setting Mostadam requirements as an objective of the retrofit process, it will ensure that the building achieve sustainability. However, Mostadam is new and there is a lack of knowledge of implementing its requirements on existing buildings. The aim of this research is to develop a framework to green existing residential buildings in Saudi Arabia to achieve Mostadam energy and water minimum requirements. The framework was developed based on an extensive keyword-based search and an analysis of 92 relevant research. The process starts with assessing the building against the minimum requirements of energy and water of Mostadam. After that, optimization phase is conducted. Building information modelling is used in the optimization phase. Energy and water efficiency optimization measures are identified from the analysed literature. Revit is used in the base model authoring and Green building studio cloud is used to simulate the energy and water efficiency measures. Then, payback period is calculated for all the efficiency measured to assess the decision making. A case study of a villa in Riyadh, Saudi Arabia is provided. result shows that the implemented efficiency measures led to an increment of 37.5% in annual energy savings and 26.1% in the annual water savings. Results shows that the application of the proposed framework supports evaluating energy and water efficiency measures to implement it on the buildings to achieve Mostadam minimum energy and water requirements. Recommendations were made for future work to bridge the knowledge gap.
ContributorsMohamed, Sara Murad (Author) / Sullivan, Kenneth (Thesis advisor) / Chong, Oswald (Committee member) / Hurtado, Kristen (Committee member) / Arizona State University (Publisher)
Created2022
Description
As the construction industry in Saudi Arabia was on its way to thriving again. Their growth was due to the unprecedented volume of planned projects such as large-scale and unique projects. Suddenly, the world was faced with one of the most disrupting events in the last century which had a devastating impact on the construction industry specifically. This paper explores mainly the impact of the COVID-19 pandemic on construction projects in Saudi Arabia. Particularly, this paper explores how the pandemic and its related events contributed to the projects' schedule disturbances. This is because most of the projects rely on manpower and supply chains which were heavily disrupted due to the protective measures. For that, a study was conducted to evaluate the impact on the construction projects in Saudi Arabia, to what extent the schedule projects were affected, and what were the main reasons for the schedule delays. The research relied on a field survey and schedule analysis for 12 projects which resulted in identifying several causes of delays and the delayed durations that the projects in Saudi Arabia were facing. This research allows those in construction fields to identify the main causes of delays in order to avoid or minimize the impact of these issues on future projects.
ContributorsObeid, Muhammad Hasan Hani (Author) / Ariaratnam, Samuel (Thesis advisor) / El Asmar, Mounir (Committee member) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2021
Description
MicroRNAs (miRNAs) are 17-22 nucleotide non-coding RNAs that regulate gene expression by targeting non-complementary elements in the 3’ untranslated regions (3’UTRs) of mRNAs. miRNAs, which form complex networks of interaction that differ by tissue and developmental stage, display conservation in their function across metazoan species. Yet much remains unknown regarding their biogenesis, localization, strand selection, and their absolute abundance due to the difficulty of detecting and amplifying such small molecules. Here, I used an updated HT qPCR-based methodology to follow miRNA expression of 5p and 3p strands for all 190 C. elegans miRNAs described in miRBase throughout all six developmental stages in triplicates (total of 9,708 experiments), and studied their expression levels, tissue localization, and the rules underlying miRNA strand selection. My study validated previous findings and identified novel, conserved patterns of miRNA strand expression throughout C. elegans development, which at times correlate with previously observed developmental phenotypes. Additionally, my results highlighted novel structural principles underlying strand selection, which can be applied to higher metazoans.
Though optimized for use in C. elegans, this method can be easily adapted to other eukaryotic systems, allowing for more scalable quantitative investigation of miRNA biology and/or miRNA diagnostics.
ContributorsMeadows, Dalton Alexander (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Murugan, Vel (Committee member) / Wilson-Rawls, Jeanne (Committee member) / Arizona State University (Publisher)
Created2023
Description
The world faces significant environmental and social challenges due to high economic development, population growth, industrialization, rapid urbanization, and unsustainable consumption. Global communities are taking the necessary measures to confront these international challenges and applying sustainable development principles across all sectors. Construction is a critical driving instrument of economic activity, and to achieve sustainable development, it is vital to transform conventional construction into a more sustainable model. The research investigated sustainable construction perceptions in Kuwait, a rapidly growing country with a high volume of construction activities. Kuwait has ambitious plans to transition into a more sustainable economic development model, and the construction industry needs to align with these plans. This research aims to identify the characteristics of sustainable construction applications in the Kuwaiti construction market, such as awareness, current perceptions, drivers and barriers, and the construction regulations' impact. The research utilized a qualitative approach to answer research questions and deliver research objectives by conducting eleven Semi-structured interviews with experienced professionals in the Kuwaiti construction market to collect rich data that reflects insights and understandings of the Kuwaiti construction industry. The Thematic analysis of the data resulted in six themes and one sub-theme that presented reflections, insights, and perspectives on sustainable construction perceptions in the Kuwaiti construction market. The research findings reflected poor sustainable construction awareness and poor environmental and social application in the construction industry, the determinant role of construction regulations in promoting sustainable construction. and barriers and drivers to sustainable construction applications. The research concluded with answers to research questions, delivery of research objectives, and an explanation of sustainable construction perceptions in the Kuwaiti construction market.
Contributorsalsalem, mohammad salem (Author) / Duran, Melanie (Thesis advisor) / Chong, Oswald (Committee member) / Sullivan, Kenneth (Committee member) / Grau, David (Committee member) / Arizona State University (Publisher)
Created2023
Description
During the rapid growth of infrastructure projects globally, countries pay high environmental and social costs as a result of the impacts caused from utilizing the traditional open-cut utility installation method that still widely being used in Egypt. For that, it was essential to have alternatives to reduce these environmental impacts and social costs; however, there are some obstacles that prevent the implementation and the realization of these alternatives.This research is conducted mainly to evaluate the environmental impacts of open-cut excavation vs. trenchless technology in Egypt, through two main methodologies. Firstly, a field survey that aims to measure knowledge of people working in the Egyptian construction industry of trenchless technology, and the harms caused from keeping utilizing open-cut for installing all kinds of underground utilities. In addition to investigating the reasons behind not relying on trenchless technology as a safe alternative for open-cut in Egypt.
Furthermore, in order to compare the greenhouse gases emissions resulted from both open-cut vs trenchless technology, a real case study is applied quantifying the amounts of the resulted greenhouse gases from each method. The results show that greenhouse gases emissions generated from open-cut were extremely higher than that of horizontal directional drilling as a trenchless installation method.
ContributorsKhedr, Ahmed Mossad Saeed Hafez (Author) / Ariaratnam, Samuel (Thesis advisor) / El Asmar, Mounir (Committee member) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2023
Description
Given the importance of buildings as major consumers of resources worldwide, several organizations are working avidly to ensure the negative impacts of buildings are minimized. The U.S. Green Building Council's (USGBC) Leadership in Energy and Environmental Design (LEED) rating system is one such effort to recognize buildings that are designed to achieve a superior performance in several areas including energy consumption and indoor environmental quality (IEQ). The primary objectives of this study are to investigate the performance of LEED certified facilities in terms of energy consumption and occupant satisfaction with IEQ, and introduce a framework to assess the performance of LEED certified buildings.
This thesis attempts to achieve the research objectives by examining the LEED certified buildings on the Arizona State University (ASU) campus in Tempe, AZ, from two complementary perspectives: the Macro-level and the Micro-level. Heating, cooling, and electricity data were collected from the LEED-certified buildings on campus, and their energy use intensity was calculated in order to investigate the buildings' actual energy performance. Additionally, IEQ occupant satisfaction surveys were used to investigate users' satisfaction with the space layout, space furniture, thermal comfort, indoor air quality, lighting level, acoustic quality, water efficiency, cleanliness and maintenance of the facilities they occupy.
From a Macro-level perspective, the results suggest ASU LEED buildings consume less energy than regional counterparts, and exhibit higher occupant satisfaction than national counterparts. The occupant satisfaction results are in line with the literature on LEED buildings, whereas the energy results contribute to the inconclusive body of knowledge on energy performance improvements linked to LEED certification. From a Micro-level perspective, data analysis suggest an inconsistency between the LEED points earned for the Energy & Atmosphere and IEQ categories, on one hand, and the respective levels of energy consumption and occupant satisfaction on the other hand. Accordingly, this study showcases the variation in the performance results when approached from different perspectives. This contribution highlights the need to consider the Macro-level and Micro-level assessments in tandem, and assess LEED building performance from these two distinct but complementary perspectives in order to develop a more comprehensive understanding of the actual building performance.
This thesis attempts to achieve the research objectives by examining the LEED certified buildings on the Arizona State University (ASU) campus in Tempe, AZ, from two complementary perspectives: the Macro-level and the Micro-level. Heating, cooling, and electricity data were collected from the LEED-certified buildings on campus, and their energy use intensity was calculated in order to investigate the buildings' actual energy performance. Additionally, IEQ occupant satisfaction surveys were used to investigate users' satisfaction with the space layout, space furniture, thermal comfort, indoor air quality, lighting level, acoustic quality, water efficiency, cleanliness and maintenance of the facilities they occupy.
From a Macro-level perspective, the results suggest ASU LEED buildings consume less energy than regional counterparts, and exhibit higher occupant satisfaction than national counterparts. The occupant satisfaction results are in line with the literature on LEED buildings, whereas the energy results contribute to the inconclusive body of knowledge on energy performance improvements linked to LEED certification. From a Micro-level perspective, data analysis suggest an inconsistency between the LEED points earned for the Energy & Atmosphere and IEQ categories, on one hand, and the respective levels of energy consumption and occupant satisfaction on the other hand. Accordingly, this study showcases the variation in the performance results when approached from different perspectives. This contribution highlights the need to consider the Macro-level and Micro-level assessments in tandem, and assess LEED building performance from these two distinct but complementary perspectives in order to develop a more comprehensive understanding of the actual building performance.
ContributorsChokor, Abbas (Author) / El Asmar, Mounir (Thesis advisor) / Chong, Oswald (Committee member) / Parrish, Kristen (Committee member) / Arizona State University (Publisher)
Created2015
Description
Patients with malignant brain tumors have a median survival of approximately 15 months following diagnosis, regardless of currently available treatments which include surgery followed by radiation and chemotherapy. Improvement in the survival of brain cancer patients requires the design of new therapeutic modalities that take advantage of common phenotypes. One such phenotype is the metabolic dysregulation that is a hallmark of cancer cells. It has therefore been postulated that one approach to treating brain tumors may be by metabolic alteration such as that which occurs through the use of the ketogenic diet (KD). The KD is high-fat, low-carbohydrate diet that induces ketosis and has been utilized for the non-pharmacologic treatment of refractory epilepsy. It has been shown that this metabolic therapy enhances survival and potentiates standard therapy in mouse models of malignant gliomas, yet the anti-tumor mechanisms are not fully understood.
The current study reports that KetoCal® (KC; 4:1 fat:protein/carbohydrates), fed ad libitum, alters hypoxia, angiogenic, and inflammatory pathways in a mouse model of glioma. Tumors from animals maintained on KC showed reduced expression of the hypoxia marker carbonic anhydrase 9 (CA IX), a reduction in hypoxia inducible factor 1-alpha (HIF-1α) and decreased activation of nuclear factor kappa B (NF-κB). Animals maintained on KC also showed a reduction in expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased microvasculature in their tumors. Further, peritumoral edema was significantly reduced in animals fed the KC and protein analysis showed significantly altered expression of the tight junction protein zona occludens-1 (ZO-1) and the water channeling protein aquaporin-4 (AQP4), both of which have been implicated in malignant processes in glioma, including the formation of peritumoral edema in patients. Taken together the data suggests that KC alters multiple processes involved in malignant progression of gliomas. A greater understanding of the effects of the ketogenic diet as an adjuvant therapy will allow for a more rational approach to its clinical use.
The current study reports that KetoCal® (KC; 4:1 fat:protein/carbohydrates), fed ad libitum, alters hypoxia, angiogenic, and inflammatory pathways in a mouse model of glioma. Tumors from animals maintained on KC showed reduced expression of the hypoxia marker carbonic anhydrase 9 (CA IX), a reduction in hypoxia inducible factor 1-alpha (HIF-1α) and decreased activation of nuclear factor kappa B (NF-κB). Animals maintained on KC also showed a reduction in expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased microvasculature in their tumors. Further, peritumoral edema was significantly reduced in animals fed the KC and protein analysis showed significantly altered expression of the tight junction protein zona occludens-1 (ZO-1) and the water channeling protein aquaporin-4 (AQP4), both of which have been implicated in malignant processes in glioma, including the formation of peritumoral edema in patients. Taken together the data suggests that KC alters multiple processes involved in malignant progression of gliomas. A greater understanding of the effects of the ketogenic diet as an adjuvant therapy will allow for a more rational approach to its clinical use.
ContributorsWoolf, Eric C (Author) / Scheck, Adrienne C (Thesis advisor) / Lake, Douglas F (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2014
Description
The performance of the Alpha Sprayed Polyurethane Foam (SPF) roofing system is perceived as not an economical option when compared to a 20-year modified bitumen roofing system. Today, the majority of roofs are being replaced, rather than newly installed. The coating manufacturer, Neogard, implemented the Alpha roofing program to identify the best contractors in the industry and to measure their roof performance. The Alpha roof system has shown consistent high performance on over 230 million square feet of surveyed roof. The author proposes to identify if the Alpha roof system is renewable, has proven performance that competes with the traditional modified roofing system, and is a more economical option by evaluating an Alpha roof system installation and the performance of a 29-year-old Alpha roof system. The Dallas Independent School District utilized the Alpha program for William Lipscomb Elementary School in 2016. Dallas Fort Worth Urethane installed the Alpha SPF roof system with high customer satisfaction ratings. This roofing installation showed the value of the Alpha roof system by saving over 20% on costs for the installation and will save approximately 69% of costs on the recoating of the roof in 20 years. The Casa View Elementary School roof system was installed with a Neogard Permathane roof system in 1987. This roof was hail tested with ten drops from 17 feet 9 inches of 1-3/4-inch steel ball (9 out of 10 passed) and four drops from 17 feet 9 inches with a 3-inch diameter steel ball (2 out of 4 passed). The analysis of the passing and failing core samples show that the thickness of the top and base Alpha SPF coating is one of the major differences in a roof passing or failing the FM-SH hail test. Over the 40-year service life, the main difference of purchasing a 61,000 square feet Alpha SPF roof versus modified bitumen roof are savings of approximately $1,067,500. Past hail tests on Alpha SPF roof systems show its cost effectiveness with high customer satisfaction (9.8 out of 10), an over 40-year service life after a $6.00/SF recoat and savings of over $1M for DISD.
ContributorsZulanas, Charles J., IV (Author) / Kashiwagi, Dean T. (Thesis advisor) / Kashiwagi, Jacob S (Thesis advisor) / Chong, Oswald (Committee member) / Arizona State University (Publisher)
Created2017