Matching Items (24)
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Description
This project details the synthesis and analysis of five analogs of model compound NEt-4IB (6-[ethyl(4-isobutoxy-3-isopropylphenyl)amino]nicotinic acid), that target the retinoid-X-receptor (RXR). These molecules were synthesized by substituting, adding, or removing substituents in the nitrogen-containing ring of NEt-4IB. The parent compound is a RXR partial agonist and has proven to be

This project details the synthesis and analysis of five analogs of model compound NEt-4IB (6-[ethyl(4-isobutoxy-3-isopropylphenyl)amino]nicotinic acid), that target the retinoid-X-receptor (RXR). These molecules were synthesized by substituting, adding, or removing substituents in the nitrogen-containing ring of NEt-4IB. The parent compound is a RXR partial agonist and has proven to be effective in the treatment of type II diabetes without the unwanted side effects seen with full agonists. Many of the current drugs used to treat type II diabetes are accompanied by adverse effects including increased triglyceride levels, weight gain, and hypoglycemia. Biological evaluation with KK-Ay (obese diabetic) model mice indicates that NEt-4IB may even be more effective than current drugs on the market, like pioglitazone. As a result, it is predicted that due to such structural similarity, the analogs synthesized for this work will perform equally, if not better than, NEt-4IB.
ContributorsMaiorella, Emma Lauren (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective

Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective in the treatment of multiple types of cancer, including lung cancer. However, the disadvantages of using Bex include increased instances of hypothyroidism and excessive concentrations of blood triglycerides. If an analog of Bex can be developed which retains high affinity RXR binding similar to the 9-cis retinoic acid while exhibiting less interference for heterodimerization pathways, it would be of great clinical significance in improving the quality of life for patients with CTCL. This thesis will detail the biological profiling of additional novel (Generation Two) analogs, which are currently in submission for publication, as well as that of Generation Three analogs. The results from these studies reveal that specific alterations in the core structure of the Bex "parent" compound structure can have dramatic effects in modifying the biological activity of RXR agonists.
ContributorsYang, Joanna (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Hibler, Elizabeth (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
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Description
Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor

Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor and in return control cell differentiation and proliferation. Bexarotene targets RXR homodimerization to drive transcription of tumor suppressing genes; however, adverse reactions occur simultaneously when bound to other nuclear receptors. In this study, we used novel bexarotene analogs throughout 5 iterations synthesized in the laboratory of Dr. Wagner to test for their potency and ability to bind RXR. The aim of our study is to quantitatively measure RXR homodimerization driven by bexarotene analogs using a yeast two-hybrid system. Our results suggests there to be several compounds with higher protein activity than bexarotene, particularly in generations 3.0 and 5.0. This higher affinity for RXR homodimers may help scientists identify a compound that will minimize adverse effects and toxicity of bexarotene and serve as a better cancer treatment alternative.
ContributorsSeto, David Hua (Author) / Marshall, Pamela (Thesis director) / Wagner, Carl (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
Description
By studying organismal performance, one can gain insight regarding the evolutionary and developmental processes that shape the adult organism. Bite force is an important trait that can be linked to performance, and therefore survival, of the entire organism. In order for an animal to successfully feed upon its prey, the

By studying organismal performance, one can gain insight regarding the evolutionary and developmental processes that shape the adult organism. Bite force is an important trait that can be linked to performance, and therefore survival, of the entire organism. In order for an animal to successfully feed upon its prey, the components of the jaw, such as the skeleton and attached muscles, must be strong enough to withstand the forces required for capturing and then processing (masticating) the prey. Because sharks and skates have a fully cartilaginous skeleton, they theoretically bite off more than deemed biologically possible, these organisms, therefore, are excellent models for study when trying to understand bite performance. The goal was to measure the bite force of Leucoraja erinacea. Dissections were completed for 14 individuals, in order to expose the muscles beneath the skin. The muscles were then removed, and the mass was recorded. Calculations derived from the literature were used to determine total bite force. Linear regression was used to determine the relationship between bite force and size of the organism. The average maximum bite force of Leucoraja erinacea was determined to be roughly 23.3 Newtons (N). There was a positive relationship between bite force and size. This skate produces a much smaller bite force than many other organisms, providing insight into its ecological role in food webs. Many of the shells of commercially important prey were also much stronger than the bite forces estimated for these skates, suggesting that either the skates were not mature or large enough to feed on these prey, or, perhaps this species is unable to feed on these organisms entirely.
ContributorsBurke, Samantha Elaine (Author) / Ferry, Lara (Thesis director) / Wagner, Carl (Committee member) / School for the Science of Health Care Delivery (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description

The FDA-approved drug bexarotene has been predominantly utilized for the treatment of cutaneous T-cell lymphoma (CTLC), but has shown promise as an off label treatment for various other cancers as well as Alzheimer's disease (AD). However, harmful side effects such as hypothyroidism have catalyzed a search for alternative rexinoids which

The FDA-approved drug bexarotene has been predominantly utilized for the treatment of cutaneous T-cell lymphoma (CTLC), but has shown promise as an off label treatment for various other cancers as well as Alzheimer's disease (AD). However, harmful side effects such as hypothyroidism have catalyzed a search for alternative rexinoids which retain similar levels of RXR agonism while reducing the undesirable effects incurred by bexarotene. This honors thesis outlines the steps taken to design and synthesize novel analogues of the selective retinoid-X-receptor (RXR) agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene). Corresponding NMR spectra indicates the successful construction of four novel compounds which are structurally similar to known, biologically-evaluated rexinoids that have induced fewer side effects while stimulating greater levels of RXR selectivity as compared to bexarotene. Future In vitro analyses of these four analogues coupled with the recognized efficacy of their parent compounds demonstrate the chemotherapeutic potential of structurally modified bexarotene analogues

ContributorsDavidson, Jesse Raymond (Author) / Wagner, Carl (Thesis director) / Ball, Rebecca (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Currently, Arizona State University's West Campus offers students a Bachelor's of Science degree in Forensics. This degree program has been at ASU's West campus for over three years now and is at its capacity of 300 students due to limitations on lab space. In order to support the growth and

Currently, Arizona State University's West Campus offers students a Bachelor's of Science degree in Forensics. This degree program has been at ASU's West campus for over three years now and is at its capacity of 300 students due to limitations on lab space. In order to support the growth and provide students with a valuable experience, the Math and Natural Sciences department seeks to create a "fee-for-service" enterprise within the Forensics division. This new lab called the Arizona State University Forensic Science Center (ASU-FSC) would serve city, county, state, and federal government agencies. The mission of the ASU-FSC is to provide robust, accurate and efficient forensic services while leading innovation in research and education in forensics for Arizona, the Southwest and the country. The School of Natural Science and Mathematics has sought help from W. P. Carey School of Business students to analyze the possibility of adding a Forensics fee-for-service lab to ASU West campus. The deliverables from this report will provide a comprehensive marketing, supply chain and financial review of all aspects of the business, and will aid in the decision making process for the creation of the Arizona State University Forensic Science Center.
ContributorsBlackburn, Amy (Co-author) / Snyder, Emily (Co-author) / Dong, Tim (Co-author) / Trujillo, Rhett (Thesis director) / Ferry, Lara (Committee member) / W. P. Carey School of Business (Contributor) / Department of Supply Chain Management (Contributor) / Department of Marketing (Contributor) / Department of Management and Entrepreneurship (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Forensic anthropologists rely on the validated sex determination methods that utilize post-cranial elements in adult remains, but, recently, research has been conducted to determine adult remain sex using just the skull. Similar research for sub-adult remains is lacking the robustness and validation that adult determination methods possess. This study utilized

Forensic anthropologists rely on the validated sex determination methods that utilize post-cranial elements in adult remains, but, recently, research has been conducted to determine adult remain sex using just the skull. Similar research for sub-adult remains is lacking the robustness and validation that adult determination methods possess. This study utilized 20 crania measurements taken from CT scans of child patients with known sexes at the Phoenix Children’s Hospital to investigate if a sex determination method could be produced. The measurements were assessed with a t-Test, Linear Discriminant Analysis, and Principle Component Analysis to determine if sexual dimorphism was detectable and if the predictive model had discriminant power when the sample size was categorized by age. The results revealed that a few measurements were dimorphic, but were not statistically significant to determine the sex of a sub-adult outside of the sample population. Future investigations will remove age group classification to observe if this model can predict age.
ContributorsMani, Mary Rachel (Author) / Ferry, Lara (Thesis director) / Falsetti, Anthony (Committee member) / School of Mathematical and Natural Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
This study examines the utility of diagnostic CT scans as sources of data to quantify facial growth in children. Subadults often suffer facial trauma arising from a variety of circumstances. Pediatric surgeons are then confronted with devising surgical pre- and post-operative strategies that present numerous complications. One of these involves

This study examines the utility of diagnostic CT scans as sources of data to quantify facial growth in children. Subadults often suffer facial trauma arising from a variety of circumstances. Pediatric surgeons are then confronted with devising surgical pre- and post-operative strategies that present numerous complications. One of these involves predicting how specific areas of a child's face will change with time. The proliferation of CT scans use in pre-operative planning throughout healthcare provides potential data for addressing many concerns, including those involving facial growth. To add to the burgeoning body of literature focusing on facial growth and provide insight anatomical variation this study used data derived from CT scans from Phoenix Children's Hospital. Quantitative data derived from CTs were used to examine normative growth and develop predictive equations that surgeons can use to visualize facial change for males and female patients.
ContributorsLee, Isaac Jet (Author) / Ferry, Lara (Thesis director) / Falsetti, Anthony (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Cancer, a disease which affects many lives, has been the topic of interest for this research. Treatment options are often available to help lessen the effects of the disease and in regards to cutaneous T-cell lymphoma (CTCL), no cure currently exists. An FDA approved drug by the name of Bexarotene

Cancer, a disease which affects many lives, has been the topic of interest for this research. Treatment options are often available to help lessen the effects of the disease and in regards to cutaneous T-cell lymphoma (CTCL), no cure currently exists. An FDA approved drug by the name of Bexarotene has been developed to provide chemotherapeutic effects within CTCL. Bexarotene has also been used in trials of breast cancer, lung cancer, glioblastoma multiforme and various neurodegenerative diseases. Yet the medication often causes serious side effects including hyperthyroidism, raised triglyceride levels and cutaneous toxicity. The focus of this research is to synthesize a hydroxylated analog compound of Bexarotene in efforts to produce a molecule that provides better chemotherapeutic effects while also lessening the various side effects caused. Synthesis of the molecule followed various organic chemistry techniques and reactions to create the final product. Melting point analysis, NMR and other various characterization data helped to confirm the synthesis of the intended molecule. Preliminary bioassay data results of the analog compound showed similar potency to that of Bexarotene. Further testing, however, will be required to determine the full pharmacokinetic profile of the molecule. Future direction of the research focuses on both further testing of the hydroxylated analog as well synthesizing newer analog compounds to find a molecule that can provide the best effects within cutaneous T-cell lymphoma and the various other diseases as well.
ContributorsMinasian, Ani Christina (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description

The bull shark, Carcharhinus leucas, is a large species that it is commonly distributed worldwide in tropical and subtropical waters. Despite the bull sharks global distribution, little is known about its life history. In particular, the limited reproductive information suggests the bull shark is placental viviparous, assumed to have a

The bull shark, Carcharhinus leucas, is a large species that it is commonly distributed worldwide in tropical and subtropical waters. Despite the bull sharks global distribution, little is known about its life history. In particular, the limited reproductive information suggests the bull shark is placental viviparous, assumed to have a biennial cycle, and that newborn pup nurseries are near the coast. In order to conserve and protect any species, an understanding of the habitats where reproductive events occur is needed. In order to better understand the habitat use in Biscayne bay, Fla, and whether certain areas are critical during the reproductive cycle of bull sharks, I will evaluate circulating levels of the hormones progesterone, estradiol, and testosterone using radioimmunoassay. These samples were collected by the University of Miami opportunistically between 2012-2020 shipped to Arizona State University, where they were analyzed. For my study a total of 73 mature samples, 27 females and 46 males, were collected over the sampling period. The results indicated that Biscayne bay is an important gestation area for bull sharks. The hormonal trends for males and females demonstrated an interesting reproductive cycle, which were further supported through other placental viviparous reproductive patterns. Females had a low level of estradiol throughout most of the year, besides in the summer where there were no sharks in the bay due to movement to estuaries. During their return to the bay, there was a peak in progesterone indicating early pregnancy. Male testosterone levels indicated that there was a production in sperm right before females speculated peak in estradiol.

ContributorsJara-Aguirre, Nisi G (Author) / Sulikowski, James (Thesis director) / Ferry, Lara (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05