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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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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
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Beginning in the early 1990s, nuclear forensic science is a relatively young field that focuses on “re-establishing the history of nuclear material of unknown origin” (Mayer, et al. 2010, p. 1). Specifically, investigators compare these unknown materials, pre-detonation in this case, based on their characteristics and process history (Mayer, et

Beginning in the early 1990s, nuclear forensic science is a relatively young field that focuses on “re-establishing the history of nuclear material of unknown origin” (Mayer, et al. 2010, p. 1). Specifically, investigators compare these unknown materials, pre-detonation in this case, based on their characteristics and process history (Mayer, et al. 2010, p. 1). In 2010, the Committee of Nuclear Forensics made ten recommendations on the procedures that could lead to improvement in investigation methods. In particular, this paper discusses Recommendation 6: “The nuclear forensics community should develop and adhere to standards and procedures that are rooted in the applicable underlying principles that have been recommended for modern forensic science, including calibration using reference standards; cross-comparison with other methods; inter-laboratory comparisons; and identification, propagation, and characterization of uncertainties'' (Committee of Nuclear Forensics, 2010, p. 11). The main objective of this paper is to compile a literature review to determine how this recommendation was followed, if at all, and produce a list of suggestions that could complement any effort towards the improvement of the field. Out of the methods recommended, that which has fostered the most growth has been cross-comparison. For example, the need for human supervision has decreased, which has decreased the need for human error (Reading, et al., 2017, p. 6013). However, areas that would benefit from development are increasing the number of disciplines in the field (Croudace, et al., 2016, p. 128). These conclusions provided the basis for improvements to other existing studies like DNA and fingerprinting.

ContributorsSarraf, Yasmine (Author) / Montero, Shirly (Thesis director) / Sellner, Erin (Committee member) / van Zalen, Ed (Committee member) / Barrett, The Honors College (Contributor) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Complex Adaptive Systems (Contributor)
Created2021-12
Description

This paper examines the effects of childhood maltreatment on attachment and development. Humans are social beings; connection is at the core of human behavior. This social nature is what drives the need to form relationships with others. Relationships help humans learn and understand the social world around them relatively safely

This paper examines the effects of childhood maltreatment on attachment and development. Humans are social beings; connection is at the core of human behavior. This social nature is what drives the need to form relationships with others. Relationships help humans learn and understand the social world around them relatively safely and securely. However, to ensure that these relationships bring safety and security, the ability to do so must be established during the first 18 months of children’s lives (Kennedy & Kennedy, 2004). The relationships humans form are based on how they establish attachments, or emotional and long-term bonds and relationships, to a primary caregiver or parent as children (Bowlby, 1969). These primary attachments include secure, anxious-preoccupied, insecure-avoidant, or fearful-avoidant attachments and can have significant effects on individuals or emerging adults in early adulthood (ages 18-25). Primary attachments act as a safe and organized view of how human interactions and relationships work and act as a secure base for children to explore and successfully understand the social world around them (Feeney & Noller, 1996). However, this depends on whether or not safety, a secure base, and an organized view of relationships are formed between the caregiver and child during the first 18 months of the child’s life. Moreover, if a child experiences maltreatment such as abuse and neglect from primary caregivers during their first 18 months of life, it can severely affect what type of attachment style is formed and how development occurs in early adulthood (Connell-Corrick, 2011). Therefore, to thoroughly understand how childhood maltreatment affects attachment and development, an overview of both attachment theory and childhood maltreatment, the effects of childhood maltreatment on both attachment and development, and the importance of protective factors, interventions, and preventions will be discussed.

ContributorsMarasinghe, Parami (Author) / Arce, Alma (Thesis director) / Visconti, Kari (Committee member) / Barrett, The Honors College (Contributor) / School of Social and Behavioral Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor)
Created2023-05
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In the 1930s, George Beadle and Boris Ephrussi discovered factors that affect eye colors in developing fruit flies. They did so while working at the California Institute of Technology in Pasadena, California. (1) They took optic discs (colored fuchsia in the image) from fruit fly larvae in the third instar

In the 1930s, George Beadle and Boris Ephrussi discovered factors that affect eye colors in developing fruit flies. They did so while working at the California Institute of Technology in Pasadena, California. (1) They took optic discs (colored fuchsia in the image) from fruit fly larvae in the third instar stage of development. Had the flies not been manipulated, they would have developed into adults with vermilion eyes. (2) Beadle and Ephrussi transplanted the donor optic discs into the bodies of several types of larvae, including those that would develop with normal colored eyes (brick red), and those that would develop eyes with other shades of red, such as claret, carmine, peach, and ruby (grouped together and colored black in the image). (3a) When implanted into normal hosts that would develop brick red eyes, the transplanted optic disc developed into an eye that also was brick red. (3b) When implanted into abnormal hosts that would develop eyes of some other shade of red, the transplanted optic discs developed into eyes that were vermilion. Beadle and Ephrussi concluded that there was a factor, such as an enzyme or some other protein, produced outside of the optic disc that influenced the color of the eye that developed from the disc.

Created2016-10-11
Description

Fruit flies of the species Drosophila melanogaster develop from eggs to adults in eight to ten days at 25 degrees Celsius. They develop through four primary stages: egg, larva, pupa, and adult. When in the wild, female flies lay their fertilized eggs in rotting fruit or other decomposing material that

Fruit flies of the species Drosophila melanogaster develop from eggs to adults in eight to ten days at 25 degrees Celsius. They develop through four primary stages: egg, larva, pupa, and adult. When in the wild, female flies lay their fertilized eggs in rotting fruit or other decomposing material that can serve as food for the larvae. In the lab, fruit flies lay their fertilized eggs in a mixture of agar, molasses, cornmeal, and yeast. After roughly a day, each egg hatches into a larva. The larva eats the material it finds itself in, and for four days it grows into stages of increasing size, called first-, second-, and third-instar stages. This figure shows a third-instar larva. Each larva has sections of tissue called imaginal discs, from which various parts of the adult anatomy develop. This figure shows the imaginal discs that will develop into antennae (colored purple), eyes (colored red), brain (colored blue), and wings (colored green). After four days, the larva turns into a pupa by making a casing, similar to caterpillars, and grows within the casing. After a four-day metamorphosis, the adult fly then emerges from its pupal casing. Adult males look somewhat different from adult females, as the males have darker rear abdomen segments than do females. The warmer the temperature around the eggs, the faster the flies develop to adults.

Created2016-10-11
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This diagram shows the life cycle of Neurospora crassa, a mold that grows on bread. N. crassa can reproduce through an asexual cycle or a sexual cycle. The asexual cycle (colored as a purple circle), begins in this figure with (1a) vegetative mycelium, which are strands of mature fungus. Some

This diagram shows the life cycle of Neurospora crassa, a mold that grows on bread. N. crassa can reproduce through an asexual cycle or a sexual cycle. The asexual cycle (colored as a purple circle), begins in this figure with (1a) vegetative mycelium, which are strands of mature fungus. Some of the strands form bulbs (2a) in a process called conidiation. From those bulbs develop the conidia, which are spores. Next, (3a) a single conidium separates from its strand and elongates until it forms mycelium. The sexual cycle (colored as an orange circle) also starts with the (1b) vegetative mycelium. The strands develop into a structure called the proto-perithecium, and reproduction involves the proto-perithecium interacting with the conidia from a different mycelium. Reproduction also involves two mating types, called type A and type a. In reproduction, type A pairs with type a, and a conidium can be of either type, as can a proto-perithecium. A proto-perithecium fertilized by a conidium of the opposite mating type (2b) will develop into a perithecium. Inside the perithecium, croziers develop and mature into asci. (3b) In a maturing ascus, there are two nuclei (one represented as a white circle and one as a black circle), one of which comes from the conidium and the other from the proto-perithecium. Each nuclei has only one set of chromosomes (haploid). The two haploid nuclei fuse into a diploid nucleus (represented as a half black half white circle). The nucleus then divides, separating into two nuclei each with one set of chromosomes. Those nuclei duplicate themselves (represented as two white circles and two black circles), and then all the nuclei duplicate themselves again (represented as four white circles and four black circles). This process yields eight haploid ascospores within a mature ascus. Ascospores are spores, and function for the mold as do seeds for plants. The mature perithecium releases its ascospores (4b), which germinate and grow into mycelium. In the 1930s and 1940s, George Beadle and Ed Tatum collected the spores of irradiated N. crassa to study how genes produced enzymes.

Created2016-10-12
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In 1935, George Beadle and Boris Ephrussi developed a technique to transplant optic discs between fruit fly larvae. They developed it while at the California Institute of Technology in Pasedena, California. Optic discs are tissues from which the adult eyes develop. Beadle and Ephrussi used their technique to study the

In 1935, George Beadle and Boris Ephrussi developed a technique to transplant optic discs between fruit fly larvae. They developed it while at the California Institute of Technology in Pasedena, California. Optic discs are tissues from which the adult eyes develop. Beadle and Ephrussi used their technique to study the development of the eye and eye pigment. (1) The experimenter dissects a donor larva, which is in the third instar stage of development, and removes the optic disc (colored red) with a micropipette. Because the antenna disc is attached to the optic disc, they are often removed and transplanted together. (2) The experimenter then implants the optic disc into a host larva, in the part of the host that will develop into an adult abdomen. As the host larva matures to adulthood, the implanted optic disc develops into an eye inside the body cavity of the adult. (3) The adult host has an eye within its body, which Beadle and Ephrussi found by dissecting the adult hosts. If the antenna disc was also transplanted, sometimes the resulting eye developed with an antenna attached.

Created2016-10-11
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In 1893, Julia Barlow Platt published her research on the origins of cartilage in the developing head of the common mudpuppy (Necturus maculosus) embryo. The mudpuppy is an aquatic salamander commonly used by embryologists because its large embryonic cells and nuclei are easy to see. Platt followed the paths of

In 1893, Julia Barlow Platt published her research on the origins of cartilage in the developing head of the common mudpuppy (Necturus maculosus) embryo. The mudpuppy is an aquatic salamander commonly used by embryologists because its large embryonic cells and nuclei are easy to see. Platt followed the paths of cells in developing mudpuppy embryos to see how embryonic cells migrated during the formation of the head. With her research, Platt challenged then current theories about germ layers, the types of cells in an early embryo that develop into adult cells. In most organisms' development, three types of germ layers are responsible for the formation of tissues and organs. The outermost layer is called ectoderm, the middle layer mesoderm, and the innermost layer endoderm, although Platt called it entoderm. Platt's research provided a basis for scientists to clarify the destination or function of the germ layers in vertebrates' development.

Created2017-03-06
Description

Arthur Earl Walker was a medical researcher and physician who studied the brain and neurosurgery in the United States during the twentieth century. Walker examined the connections of the thalamus to the rest of the brain and how the thalamus coordinates sensory signals. The thalamus is a cluster of nerve

Arthur Earl Walker was a medical researcher and physician who studied the brain and neurosurgery in the United States during the twentieth century. Walker examined the connections of the thalamus to the rest of the brain and how the thalamus coordinates sensory signals. The thalamus is a cluster of nerve cells located between the two hemispheres of the brain and it is responsible for consciousness and sensory interpretation. While studying the thalamus, Walker noticed that cerebral spinal fluid, the clear fluid surrounding the brain and spinal cord, sometimes became obstructed in certain parts of the brain in infants. Scientists linked the cerebral spinal fluid obstruction with a congenital brain malformation, later called Dandy-Walker Syndrome. Walker's work on the brain and cerebral spinal fluid enabled early diagnosis and treatment for complications in the development of the brain.

Created2017-03-07