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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
Heterogeneous musculoskeletal tissues, such as the tendon-bone junction, is crucial for transferring mechanical loading during human physical activity. This region, also known as the enthesis, is composed of a complex extracellular matrix with gradient fiber orientations and chemistries. These different physical and chemical properties are crucial in providing the support

Heterogeneous musculoskeletal tissues, such as the tendon-bone junction, is crucial for transferring mechanical loading during human physical activity. This region, also known as the enthesis, is composed of a complex extracellular matrix with gradient fiber orientations and chemistries. These different physical and chemical properties are crucial in providing the support that these junctions need in handling mechanical loading of everyday activities. Currently, surgical restorative procedures for a torn enthesis entail a very invasive technique of suturing the torn tendon onto the bone. This results in improper reinjury. To circumvent this issue, one common strategy within tissue engineering is to introduce a biomaterial scaffold which acts as a template for the local damaged tissue. Electrospinning can be utilized to fabricate a fibrous material to recapitulate the structure of the extracellular matrix. Currently electrospinning techniques only allow the creation of scaffold that consists of only one orientation and material. In this work, we investigated a multicomponent, magnetically assisted, electrospinning technique to fabricate a fiber alignment and chemical gradient scaffold for tendon-bone repair
ContributorsLe, Minh (Author) / Holloway, Julianne (Thesis director) / Green, Matthew (Committee member) / W.P. Carey School of Business (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Scientific literacy is a critical part of the education of high school students. Students can demonstrate literacy in science by being able to read and write scientific reports as well as recognize and discuss how science affects daily lives. However, many teachers are not familiar with the topic and do

Scientific literacy is a critical part of the education of high school students. Students can demonstrate literacy in science by being able to read and write scientific reports as well as recognize and discuss how science affects daily lives. However, many teachers are not familiar with the topic and do not have the resources necessary to implement it into their classrooms. This project attempts to create a website that compiles information from many sources to one concise location that is simple for teachers to use. The goal of the website is to provide teachers with a resource that they can access and use quickly despite their busy schedules. The information provided is easily translatable into a classroom, and examples of lessons as well as links to resources are provided. Considerations of difficulties such as the need to prepare students for standardized tests as well as limited budgets were brought into consideration when choosing the concepts suggested for teachers. Aspects of scientific literacy addressed are: project based learning, virtual labs, apprenticeship programs, and peer mediated learning strategies. The project also addresses how demographics that are represented at lower levels in science can be aided. These groups include female students, minorities, and students with High Functioning Autism (HFA). The website portion of the project is accompanied by a paper that summarizes the research findings as well as the personal reaction of the author and how her teaching has been affected by the study. Upon completion of the project the website will be shared with school districts across Phoenix to provide teachers with access to the resources compiled in it.
ContributorsBlome, Rebecca Ellen (Author) / Marshall, Pamela (Thesis director) / Hart, Juliet (Committee member) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.

ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05
Description
This research examines the impact of films about corporate scandals stemming from environmental disasters, specifically the film ​Dark Waters ​which details the decade-long toxic chemical release by DuPont. It will also explore what distinguishes these kinds of documentary films as successful and if they result in corporate change. Some films

This research examines the impact of films about corporate scandals stemming from environmental disasters, specifically the film ​Dark Waters ​which details the decade-long toxic chemical release by DuPont. It will also explore what distinguishes these kinds of documentary films as successful and if they result in corporate change. Some films about corporate injustices have been successful in shaping viewers’ opinions and have brought about actual changes in targeted corporations’ behaviors. However, in some instances, even though a film may hurt the public image of the corporation, it does not actually affect the operation of the business. The recently released film ​Dark Waters ​details the story of the lawyer and farmer behind the lawsuit that exposed the toxic chemical release by DuPont. The film chronicles how the lawsuit revealed how DuPont ignored and even tried to cover up how its chemicals were poisoning its own workers and the surrounding communities. It remains to be seen if this film will result in DuPont actually changing the ways it does business. In this research, I analyze three documentary films involving corporate scandals with environmental ramifications and determine if any changes were made as a result of the films and what aspects of these films caused them to be successful. My findings indicate that there are many factors that dictate whether or not a film is successful in bringing about change at the corporate level. Some of the factors include the type of corporation, how many people the scandal or environmental disaster affected, and where the incidents took place. Also, certain aspects of the film itself such as being directed or produced by well-known and respected directors and producers as well as employing famous actors can make a difference in the film’s overall impact.
ContributorsDelgado, Morgan Elyse (Author) / Ingram-Waters, Mary (Thesis director) / Hines, Taylor (Committee member) / Chemical Engineering Program (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05