Matching Items (113)
Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Vitamins and minerals are, by definition, essential substances that are necessary for good health, and needed by every cell and organ to function appropriately. A deficiency of any one vitamin or mineral can be very serious. Although a very healthy diet rich in vegetables, fruits, and protein can provide sufficient amounts of most vitamins and minerals, many people do not consume an adequate diet. During pregnancy, there is an increased need for vitamins and minerals to promote a healthy pregnancy and a healthy baby. Prenatal supplements are intended to supplement a normal diet to ensure that adequate amounts of vitamins and minerals are consumed. The US Food and Drug Administration (FDA) has established Recommended Dietary Allowances for total vitamin/mineral intake from food and supplements, but they have not established recommendations for prenatal supplements. Therefore, there is a very wide variation in the content and quality of prenatal supplements. Many prenatal supplements contain only minimal levels of some vitamins and few or no minerals, in order to minimize cost and the number of pills. This results in insufficient vitamin/mineral supplementation for many women, and hence does not fully protect them or their children from pregnancy complications and health problems. Therefore, we have created our own set of recommendations for prenatal supplements. Our recommendations are based primarily on four sources: 1) FDA's Recommended Daily Allowances for pregnant women, which are estimated to meet the needs of 97.5% of healthy pregnant women. 2) FDA's Tolerable Upper Limit, which is the maximum amount of vitamins/minerals that can be safely consumed without any risk of health problems. 3) National Health and Nutrition Examination Survey (NHANES), which evaluates the average intake of vitamins and minerals by women ages 20-40 years in the US 4) Research studies on vitamin/mineral deficiencies or vitamin/mineral supplementation during pregnancy, and the effect on pregnancy, birth, and child health problems. In summary, the RDA establishes minimum recommended levels of vitamin/mineral intake from all sources, and the NHANES establishes the average intake from foods. The difference is what needs to be consumed in a supplement, on average. However, since people vary greatly in the quality of their diet, and since most vitamins and minerals have a high Tolerable Upper Limit, we generally recommend more than the difference between the RDA and the average NHANES. Vitamins generally have a larger Tolerable Upper Limit than do minerals. So, we recommend that prenatal vitamin/mineral supplements contain 100% of the RDA for most vitamins, and about 50% of the RDA for most minerals. However, based on additional research studies described below, in some cases we vary our recommendations from those averages.
ContributorsSorenson, Jacob (Author) / Adams, James (Thesis director) / Pollard, Elena (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Genetic manipulation of human cell lines has widespread applications in biomedical research ranging from disease modeling to therapeutic development. Human cells are generally difficult to genetically engineer, but exogenous nucleic acids can be expressed by viral, chemical, or nonchemical means. Chemical transfections are simpler in practice than both viral and nonchemical delivery of genetic material, but often suffer from cytotoxicity and low efficiency. Novel aminoglycoside antibiotic-derived lipopolymers have been synthesized to mediate transgene delivery to human cells. These polymers are comprised of either paromomycin or apramycin crosslinked with glycerol diglycidylether and derivatized with stearoyl chloride in varying molar ratios. In this work, three previously identified target lipopolymers were screened against a library of human embryonic and induced pluripotent stem cell lines. Cells were transfected with a plasmid encoding green fluorescent protein (GFP) and expression was quantified with flow cytometry 48 hours after transfection. Transfection efficiency was evaluated between three distinct lipopolymers and four lipopolymer:DNA mass ratios. GFP expression was compared to that of cells transfected with commercially available chemical gene delivery reagent controls\u2014JetPEI, Lipofectamine, and Fugene\u2014at their recommended reagent:DNA ratios. Improved transgene expression in stem cell lines allows for improved research methods. Human stem cell-derived neurons that have been genetically manipulated to express phenotypic characteristics of aging can be utilized to model neurodegenerative diseases, elucidating information about these diseases that would be inaccessible in unmanipulated tissue.
ContributorsMehta, Frea (Author) / Brafman, David (Thesis director) / Rege, Kaushal (Committee member) / Chemical Engineering Program (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
the project led by Professor Emma Frow, researching of stem cell clinics focused on stem cell applications, adherence to FDA guidelines, and characterization of information available and physician credentials. Regenerative medicine clinics commonly offered stem cell therapy, but introduced platelet rich plasma (PRP) and prolotherapy as regenerative therapies.
PRP and Prolotherapy are individual treatments that were even suggested and used in combination with stem cell therapies. Prolotherapy predates PRP as a chemical irritant therapy originally used to sclerose tissues. Prolotherapy is meant to stimulate platelet derived growth factors release to improve tissue healing response. Prolotherapy shows negligible efficacy improvements over corticosteroids, but may have underlying side effects from being an irritant. PRP is a more modern therapy for improved healing. Speculations state initial use was in an open heart surgery to improve healing post-surgery. PRP is created via centrifugation of patient blood to isolate growth factors by removing serum and other biological components to increase platelet concentration. PRP is comparable to corticosteroid injections in efficacy, but as an autologous application, there are no side effects making it more advantageous. Growth factors induce healing response and reduce inflammation. Growth factors stimulate cell growth, proliferation, differentiation, and stimulate cellular response mechanism such as angiogenesis and mitogenesis. The growth factor stimulation of PRP and prolotherapy both assist stem cell proliferation. Additional research is needed to determine differential capacity to ensure multipotent stem cells regenerate the correct cell type from the increased differential capacity offered by growth factor recruitment. The application of combination therapy for stem cells is unsubstantiated and applications violate FDA ‘minimal manipulation’ guidelines.
PRP and Prolotherapy are individual treatments that were even suggested and used in combination with stem cell therapies. Prolotherapy predates PRP as a chemical irritant therapy originally used to sclerose tissues. Prolotherapy is meant to stimulate platelet derived growth factors release to improve tissue healing response. Prolotherapy shows negligible efficacy improvements over corticosteroids, but may have underlying side effects from being an irritant. PRP is a more modern therapy for improved healing. Speculations state initial use was in an open heart surgery to improve healing post-surgery. PRP is created via centrifugation of patient blood to isolate growth factors by removing serum and other biological components to increase platelet concentration. PRP is comparable to corticosteroid injections in efficacy, but as an autologous application, there are no side effects making it more advantageous. Growth factors induce healing response and reduce inflammation. Growth factors stimulate cell growth, proliferation, differentiation, and stimulate cellular response mechanism such as angiogenesis and mitogenesis. The growth factor stimulation of PRP and prolotherapy both assist stem cell proliferation. Additional research is needed to determine differential capacity to ensure multipotent stem cells regenerate the correct cell type from the increased differential capacity offered by growth factor recruitment. The application of combination therapy for stem cells is unsubstantiated and applications violate FDA ‘minimal manipulation’ guidelines.
ContributorsKrum, Logan (Author) / Frow, Emma (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
In injection molded plastic parts, knit lines occur where opposing streams of material fuse together while the mold cavity fills. When parts with knit lines experience external loading, the knit lines cause areas of mechanical weakness. This weakness is especially drastic in fiber-reinforced polymers due to an unfavorable orientation of fibers at the knit line. A possible way to reduce the impact of knit lines is to incorporate overflow tabs into the mold design. An overflow tab is a chamber attached to the mold cavity that provides an extra space for the end of material flow to occur. Research shows that overflow tabs improve the fiber orientation at the knit line, resulting in increased mechanical strength. The goal of this study is to utilize overflow tabs to optimize the knit line strength of nylon 6-6 that is 30% carbon fiber reinforced. In this project, an initial overflow tab is first designed. Then four modifications are made to the tab design, each altering a separate variable while holding the others constant. The design changes explored for the tab in this project include adding radii to the inlet, shifting the inlet location, increasing the inlet cross-sectional area by 50%, and increasing the tab chamber volume by 50%. Specimens were molded using the initial tab design and the modified tab designs. Testing for this experiment consists of three specimens of each type for three-point bending tests, and five specimens of each type for tensile tests. The material properties analyzed are the flexural modulus, flexural strength, tensile modulus, and tensile strength. From the testing, the tab with the 50% increased volume consistently yielded the highest results and showed large improvement from the initial tab design. However, the other three tab modifications either showed negative change or slight improvement from the initial tab design. Based on the results of this study, the overflow tab volume is the most beneficial design parameter to adjust.
ContributorsJones, Justin Michael (Author) / Adams, James (Thesis director) / Wamsley, Steven (Committee member) / Computer Science and Engineering Program (Contributor) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The purpose of this honors project is to analyze the difference between different powder separation techniques, and their suitability for my capstone project – ‘Effect of Powder Reuse on DMLS (Direct Metal Laser Sintering) Product Integrity’. Due to the nature of my capstone project, my group needs to characterize foreign contaminants in IN 718 (Ni-based superalloy) powder with a mean diameter around 40um. In order to clearly analyze the contaminants and recycle useful IN 718 powders, powder separation is favorable since the filtered samples will be much easier to characterize rather than inspect all the powders at once under microscope. By conducting literature review, I found that powder separation is commonly used in Geology, and Chemistry department. To screen which combination of techniques could be the best for my project, I have consulted several research specialists, obtained adequate knowledge about powder separation. Accordingly, I will summarize the pros and cons of each method with regard the specific project that I am working on, and further explore the impacts of each method under economical, societal, and environmental considerations. Several powder separation techniques will be discussed in details in the following sections, including water elutriation, settling column, magnetic separation and centrifugation. In addition to these methods, sieving, water tabling and panning will be briefly introduced. After detailed comparison, I found that water elutriation is the most efficient way to purity IN718 powder for reuse purpose, and recovery rate is as high as 70%, which could result in a significant reduction in the manufacturing cost for Honeywell since currently Honeywell only use virgin powders to build parts, and 90% of the leftover powders are discarded.
ContributorsLuo, Zheyu (Author) / Adams, James (Thesis director) / Tasooji, Amaneh (Committee member) / Materials Science and Engineering Program (Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Honeywell is currently extending the reach of additive manufacturing (AM) in its product line and expects to produce as much as 40% of its inventory through AM in five years. Additive manufacturing itself is expected to grow into a $3.1 billion dollar industry in the next 5 to 10 years. Reusing IN 718 powder, a nickel-based super alloy metal powder, is an ideal option to reduce costs as well as reduce waste because it can be used with additive manufacturing, but the main obstacles are lack of procedure standardization and product quality assurances from this process. The goal of the capstone project, "Effect of Powder Reuse on DMLS (Direct Metal Laser Sintering) Product Integrity," is to create a powder characterization protocol in order to determine if the IN 718 powder can be reused and what effect the IN 718 reused powder has on the mechanical properties of the products Honeywell fabricates. To provide context and impact of this capstone project, this paper serves to identify the benefits of AM for Honeywell and the cost effectiveness of reusing the powder versus using virgin powder every time. It was found that Honeywell's investment in AM is due to the cost effectiveness of AM, versatility in product design, and to ensure Honeywell remains competitive in the future. In terms of reducing expenses, reusing powder enables costs to be approximately 45% less than using virgin powder. With these key pieces of information, the motivations for this capstone project are understood to a fuller and more profound degree.
ContributorsQuigley, Elizabeth (Co-author) / Luo, Zheyu (Co-author) / Murella, Anoosha (Co-author) / Lee, Wey Lyn (Co-author) / Adams, James (Thesis director) / Tasooji, Amaneh (Committee member) / Materials Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Autism Spectrum Disorder is a disorder that makes learning, socializing and daily living much more challenging for affected children and adults because of their atypical behaviors. A few examples of these behaviors are repetitive movements, impulsive actions, inability to communicate in a social setting, and many more. There is a stigma behind autism that is caused by those who are not well informed on the disorder. These people lack information, and in the past, it was assumed that the disorder is caused by "bad parenting." The parents are then afraid of social shame brought upon them by their child and neglect or avoid a diagnosis for their child's disorder. This becomes a vicious cycle that has negative effects on the affected individuals and their loved ones. Neglect of a diagnosis may also be caused by misinformation interpreted by the parents as their child develops. The parents do not realize this child developing outside of normal behavioral patterns. Years of research have been done to attempt to alleviate the symptoms of autism and cure the disorder. The Autism and Asperger's Program at ASU has developed a year-long dietary plan that increases supplementation to alleviate nutritional deficiencies in participants with autism. These deficiencies include vitamins, minerals, essential fatty acids, sulfate, carnitine, and digestive enzymes such as sucrase, maltase, and lactase. The participants were also put on a gluten-free casein-free diet toward the end of the study. To test the effectiveness of the treatment, the Severity of Autism Scale (SAS) and Social Responsiveness Scales (SRS) were used. The SAS tested the overall severity of ASD participants by rating them from one to ten, ten being "very severe" in terms of ASD symptoms. The results of this scale were compared at the beginning of the study (day 0) and at the end of the study (day 365). The SRS tested the social responsiveness of participants in the form of overall SRS and five subscales that included awareness, cognition, communication, motivation, and mannerisms. These results were also compared at the beginning and end of the study. After analysis of the data, there seemed to be no correlation between age and severity of autism/social responsiveness of participants. There was also no statistically significant data to suggest that there was a correlation between gender and severity of autism/social responsiveness of participants. However, there was statistically significant evidence that the treatment group did improve over the non-treatment/delayed treatment group in both the SAS and SRS. Neither age nor gender had a significant effect on the effectiveness of the treatment. These positive findings suggest that the integrated dietary
utritional therapy was beneficial, and future research on dietary treatments for autism and other disorders is recommended. This may also further discoveries of affected epigenomes with regards to nutritional treatments in disorders like ASD. The epigenome is the methylation and demethylation of the genome that mediates gene expression.
utritional therapy was beneficial, and future research on dietary treatments for autism and other disorders is recommended. This may also further discoveries of affected epigenomes with regards to nutritional treatments in disorders like ASD. The epigenome is the methylation and demethylation of the genome that mediates gene expression.
ContributorsGutgsell, Crystal Megan (Author) / Adams, James (Thesis director) / Pollard, Elena (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Current research into live-cell dynamics, particularly those relating to chromatin structure and remodeling, are limited. The tools that are used to detect state changes in chromatin, such as Chromatin Immunoprecipitation and qPCR, require that the cell be killed off. This limits the ability of researchers to pinpoint changes in live cells over a longer period of time. As such, there is a need for a live-cell sensor that can detect chromatin state changes. The Chromometer is a transgenic chromatin state sensor designed to better understand human cell fate and the chromatin changes that occur. HOXD11.12, a DNA sequence that attracts repressive Polycomb group (PCG) proteins, was placed upstream of a core promoter-driven fluorescent reporter (AmCyan fluorescent protein, CFP) to link chromatin repression to a CFP signal. The transgene was stably inserted at an ectopic site in U2-OS (osteosarcoma) cells. Expression of CFP should reflect the epigenetic state at the HOXD locus, where several genes are regulated by Polycomb to control cell differentiation. U2-OS cells were transfected with the transgene and grown under selective pressure. Twelve colonies were identified as having integrated parts from the transgene into their genomes. PCR testing verified 2 cell lines that contain the complete transgene. Flow cytometry indicated mono-modal and bimodal populations in all transgenic cell colonies. Further research must be done to determine the effectiveness of this device as a sensor for live cell state change detection.
ContributorsBarclay, David (Co-author) / Simper, Jan (Co-author) / Haynes, Karmella (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
A novel approach, the Invariant Based Theory of Composites and the "Trace" method it proposes, has the potential to reduce aerospace composite development times and costs by over 30% thus reinvigorating the development process and encouraging composite technology growth. The "trace" method takes advantage of inherent stiffness properties of laminates, specifically carbon fiber, to make predictions of material properties used to derive design allowables. The advantages of the "trace" theory may not necessarily be specific to the aerospace industry, however many automotive manufacturers are facing environmental, social and political pressure to increase the gas mileage in their vehicles and reduce their carbon footprint. Therefore, the use of lighter materials, such as carbon fiber composites, to replace heavier metals in cars is inevitable yet as of now few auto manufacturers implement composites in their cars. The high material, testing and development costs, much like the aerospace industry, have been prohibitive to widespread use of these materials but progress is being made in overcoming those challenges. The "trace" method, while initially intended for quasi-isotropic, aerospace grade carbon-fiber laminates, still yields reasonable, and correctable, results for types of laminates as well such as with woven fabrics and thermoplastic matrices, much of which are being used in these early stages of automotive composite development. Despite the varying use of materials, the "trace" method could potentially boost automotive composites in a similar way to the aerospace industry by reducing testing time and costs and perhaps even playing a role in establishing emerging simulations of these materials.
ContributorsBrown, William Ross (Author) / Adams, James (Thesis director) / Anwar, Shahriar (Committee member) / Krause, Stephen (Committee member) / Materials Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05