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- Genre: Masters Thesis
Description
Bexarotene is a Food and Drug administration (FDA)-approved therapeutic used in the treatment of cutaneous T-cell lymphoma (CTCL). However, bexarotene therapy causes significant side effects like hyperlipidemia and hypothyroidism due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. More recently bexarotene has shown promise to reverse neurodegeneration, improve cognition and decrease levels of amyloid- β in transgenic mice expressing familial Alzheimer’s disease (AD) mutations. Bexarotene is a high affinity ligand for the retinoid X receptor (RXR) that heterodimerizes with the liver- X- receptors (LXR) and with peroxisome proliferator-activated receptor-gamma (PPARϒ) to control cholesterol efflux, inflammation, and transcriptionally upregulates the production of apolipoprotein (ApoE) in the brain. Enhanced ApoE expression may promote clearance of soluble Aβ peptides from the brain and reduce Aβ plaques, thus resolving both amyloid pathology and cognitive deficits. The present study assessed the potential of bexarotene and a group of 62 novel rexinoids to bind and activate RXR using a series of biological assays and screening methods, including: 1) a mammalian two-hybrid system (M2H) and an 2) Retinoid X Receptor response element (RXRE)-mediated reporter assays in cultured human cells. Moreover, Liver X Receptor response element (LXRE)-mediated luciferase assays were performed to analyze the ability of the novel analogs to activate LXRE - directed transcription, and to induce ApoE messenger ribonucleic acid (mRNA) in U87 glial cells. Furthermore, the most potent analogs were analyzed via quantitative polymerase chain reaction (qPCR) to determine efficacy in modulating expression of two critical tumor suppressor genes, activating transcription factor 3 (ATF3) and early growth response 3 (EGR3). Results from these multiple assays indicate that the panel of RXR ligands contains compounds with a range of activities, with some analogs capable of binding to RXR with higher affinity than others, and in some cases upregulating ApoE expression to a greater extent than bexarotene. The data suggests that minor modifications to the bexarotene core chemical structure may yield novel analogs possessing an equal or greater capacity to activate RXR and may be useful as therapeutic agents against CTCL and Alzheimer’s disease.
ContributorsReshi, Sabeeha Mushtaq (Author) / Jurutka, Peter (Thesis advisor) / Wagner, Carl (Committee member) / Marshall, Pamela (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
Microbial diversity manifests differently in different ecological niches of the body, with greater diversity generally expected in the gut, given that different locations have unique roles to play in the digestive system. Most microbial research is conducted using fecal samples, meaning the resulting microbes come from various places all throughout the intestines and not specific locations. The Integrative Human Microbiome Project (HMP2), provides a unique opportunity to study microbiomes of both the rectum and ileum through the use of biopsy samples taken from both locations. Using the data provided the microbiome compositions of the rectum and ileum were able to be studied and analyzed to showcase how those microbes associated with clinical variables. Inflammatory bowel diseases are complex diseases that are heterogeneous at clinical, immunological, molecular, genetic, and microbial levels. While it is known that those affected by these diseases have microbiomes that differ from those with healthy guts, not much is known about which changes in the microbiome represent causes rather than effects from changes in health.
ContributorsVecchio, Kurt (Author) / Zhao, Yunpeng (Thesis advisor) / Wang, Yue (Committee member) / Jurutka, Peter (Committee member) / Arizona State University (Publisher)
Created2023
Description
In this era of high-tech computer advancements and tremendous programmable computer capabilities, construction cost estimation still remains a knowledge-intensive and experience driven task. High reliance on human expertise, and less accuracy in the decision support tools render cost estimation error prone. Arriving at accurate cost estimates is of paramount importance because it forms the basis of most of the financial, design, and executive decisions concerning the project at subsequent stages. As its unique contribution to the body of knowledge, this paper analyzes the deviations and behavior of costs associated with different construction activities involved in commercial office tenant improvement (TI) projects. The aim of this study is to obtain useful micro-level cost information of various construction activities that make up for the total construction cost of projects. Standardization and classification of construction activities have been carried out based on Construction Specifications Institute’s (CSI) MasterFormat® division items. Construction costs from 51 office TI projects completed during 2015 and 2016 are analyzed statistically to understand the trends among various construction activities involved. It was found that the interior finishes activities showed a much higher cost of construction, and a comparatively higher variation than the mechanical, electrical, and plumbing (MEP) trades. The statistical analysis also revealed a huge scope of energy saving measures that could be achieved in such TI projects because of the absence of energy management systems (EMS) found in 66% of the projects.
ContributorsGhosh, Arunabho (Author) / Grau, David (Thesis advisor) / Ayer, Steven (Committee member) / Parrish, Kristen (Committee member) / Arizona State University (Publisher)
Created2016