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Description
The objective of this research was to predict the persistence of potential future contaminants in indirect potable reuse systems. In order to accurately estimate the fates of future contaminants in indirect potable reuse systems, results describing persistence from EPI Suite were modified to include sorption and oxidation. The target future contaminants studied were the approximately 2000 pharmaceuticals currently undergoing testing by United States Food and Drug Administration (US FDA). Specific organic substances such as analgesics, antibiotics, and pesticides were used to verify the predicted half-lives by comparing with reported values in the literature. During sub-surface transport, an important component of indirect potable reuse systems, the effects of sorption and oxidation are important mechanisms. These mechanisms are not considered by the quantitative structure activity relationship (QSAR) model predictions for half-lives from EPI Suite. Modifying the predictions from EPI Suite to include the effects of sorption and oxidation greatly improved the accuracy of predictions in the sub-surface environment. During validation, the error was reduced by over 50% when the predictions were modified to include sorption and oxidation. Molecular weight (MW) is an important criteria for estimating the persistence of chemicals in the sub-surface environment. EPI Suite predicts that high MW compounds are persistent since the QSAR model assumes steric hindrances will prevent transformations. Therefore, results from EPI Suite can be very misleading for high MW compounds. Persistence was affected by the total number of halogen atoms in chemicals more than the sum of N-heterocyclic aromatics in chemicals. Most contaminants (over 90%) were non-persistent in the sub-surface environment suggesting that the target future drugs do not pose a significant risk to potable reuse systems. Another important finding is that the percentage of compounds produced from the biotechnology industry is increasing rapidly and should dominate the future production of pharmaceuticals. In turn, pharmaceuticals should become less persistent in the future. An evaluation of indirect potable reuse systems that use reverse osmosis (RO) for potential rejection of the target contaminants was performed by statistical analysis. Most target compounds (over 95%) can be removed by RO based on size rejection and other removal mechanisms.
ContributorsLim, Seung (Author) / Fox, Peter (Thesis advisor) / Abbaszadegan, Morteza (Committee member) / Halden, Rolf (Committee member) / Arizona State University (Publisher)
Created2011
Description
As life expectancy increases worldwide, age related diseases are becoming greater health concerns. One of the most prevalent age-related diseases in the United States is dementia, with Alzheimer’s disease (AD) being the most common form, accounting for 60-80% of cases. Genetics plays a large role in a person’s risk of developing AD. Familial AD, which makes up less than 1% of all AD cases, is caused by autosomal dominant gene mutations and has almost 100% penetrance. Genetic risk factors are believed to make up about 49%-79% of the risk in sporadic cases. Many different genetic risk factors for both familial and sporadic AD have been identified, but there is still much work to be done in the field of AD, especially in non-Caucasian populations. This review summarizes the three major genes responsible for familial AD, namely APP, PSEN1 and PSEN2. Also discussed are seven identified genetic risk factors for sporadic AD, single nucleotide polymorphisms in the APOE, ABCA7, NEDD9, CASS4, PTK2B, CLU, and PICALM genes. An overview of the main function of the proteins associated with the genes is given, along with the supposed connection to AD pathology.
ContributorsRichey, Alexandra Emmeline (Author) / Brafman, David (Thesis director) / Raman, Sreedevi (Committee member) / School of International Letters and Cultures (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213), with the goal of establishing the state of knowledge and existing information gaps. Publications on IL toxicity were collected from the SciFinder database and sorted by cation and model organism studied. Studies focusing on pharmacokinetics and drug development were excluded, as were structure-activity relationship methods of data collection. Total publishing activity was used as a measure to gauge research and industrial usage of ILs as well as the knowledge base of toxicology. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 1.2% ± 0.62% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemicals. In vitro models and marine bacteria were the most frequently studied biological systems, contributing 18% and 15%, respectively, to the total body of IL toxicity studies. Whole animal studies (n = 87) comprised 41% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need for filling crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies.
ContributorsHeckenbach, Mary (Co-author) / Halden, Rolf (Co-author, Thesis director) / Jehn, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Thousands of human lives are lost every day due to chronic diseases, some more preventable than others. For years, the gold standard for diagnosing and monitoring these diseases has been through traditional methods such as individualized doctor-patient clinical evaluations, usually involving laboratory tests. These methods, though effective, can be costly, time-consuming, and fail to encompass an overarching perspective of the health profile of the larger population. Wastewater-based epidemiology (WBE) has successfully been employed for decades as a population-level data source informing on the consumption of licit and illicit substance use. It also is showing promise for its use as a community-wide diagnostic tool for broader public health measurements. This literature review constitutes a theoretical evaluation of the potential use of WBE for monitoring the top two deadly diseases in the United States; cardiovascular disease (CVD) and cancer. Literature-reported metabolites indicative of these diseases were evaluated to determine if they were capable of being identified and monitored in wastewater. Potential analytes include cardiac-specific troponin, α-fenotroin, and inositol. Results obtained within suggest WBE could be used as a viable and economical tool to track and monitor the top deadly diseases in human populations. This methodology could be implemented in tandem with current practices in order to provide a more holistic understanding of prevalence and risk for CVD and cancer.
ContributorsAmin, Vivek (Author) / Halden, Rolf (Thesis director) / Niebuhr, Robert (Committee member) / Bowes, Devin (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Microplastics are defined as small pieces of plastics that are less than five millimeters in size. These microplastics can vary in their appearance, are known to be harmful to aquatic life and can threaten life cycles of marine organisms because of their chemical make-up and the toxic additives used in their manufacture. Although small in size, it is hypothesized that microplastics can serve as an example of how human activities can alter ecosystems near and far. To investigate the implications and determine the potential impact of microplastics on a protected atoll’s ecosystems, red-footed booby (Sula sula) guano samples from six locations on Palmyra Atoll were acquired from North Carolina State University via The Nature Conservancy and were inspected for the presence of microplastics. Each of the guano samples were weighed and prepared via wet oxidation. Microplastic fibers were detected via stereoscope microscopy and analyzed for chemical composition via Raman spectroscopy. All six sampling locations within Palmyra Atoll contained microplastic fibers identified as polyethylene terephthalate, with North-South Causeway and Eastern Island having the highest average number of microplastic fibers found per gram of guano sample (n = 0.611). These data provide evidence that seabirds can serve as vectors for the spread of microplastic pollution. This research lends context to the widespread impact of plastic pollution and states possible implications of its presence in delicate ecosystems.
ContributorsAnderson, Alyssa Cerise (Author) / Lisenbee, Cayle (Thesis director) / Halden, Rolf (Committee member) / Rolsky, Charles (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Cell viability is an important assessment in cell culture to characterize the health of the cell population and confirm if cells are alive. Morphology or end-line assays are used to determine cell viability of entire populations. Intracellular pO2 levels is indicative of cell health and metabolism that can be used as a factor to asses cell viability in an in-line assay. Siloxane based pO2 sensing nanoprobes present a modality to visualize intracellular pO2. Using fluorescent lifetime imaging microscopy (FLIM), pO2 levels can be mapped intracellular as a highly functional in-line assay for cell viability. FLIM is an imaging modality that reconstructs an image based of its fluorescent lifetime. Nanoprobes were synthesized in different manufacturing/storage conditions. The nanoprobes for both long- and short-term storage were characterized in a cell free environment testing for changes in fluorescent intensity, average and maximum nanoprobe diameter. The nanoprobes were validated in two different culture systems, 2D and microcarrier culture systems, for human derived neural progenitor cells (NPCs) and neurons. Long- and short-term storage nanoprobes were used to label different neuronal based culture systems to asses labeling efficiency through fluorescent microscopy and flow cytometry. NPCs and neurons in each culture system was tested to see if nanoprobe labeling effected cellular phenotype for traits such as: cell proliferation, gene expression, and calcium imaging. Long-term and short-term storage nanoprobes were successfully validated for both NPCs and neurons in all culture systems. Assessments of the pO2 sensing nanoprobes will be further developed to create a highly functional and efficient in-line test for cell viability.
ContributorsLeyasi, Salma (Author) / Brafman, David (Thesis director) / Kodibagkar, Vikram (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Current methods measuring the consumption of prescription and illicit drugs are often hampered by innate limitations, the data is slow and often restricted, which can impact the relevance and robustness of the associated data. Here, wastewater-based epidemiology (WBE) was applied as an alternative metric to measure trends in the consumption of twelve narcotics within a collegiate setting from January 2018 to May 2018 at a Southwestern U.S. university. The present follow-up study was designed to identify potential changes in the consumption patterns of prescription and illicit drugs as the academic year progressed. Samples were collected from two sites that capture nearly 100% of campus-generated wastewater. Seven consecutive 24-hour composite raw wastewater samples were collected each month (n = 68) from both locations. The study identified the average consumption of select narcotics, in units of mg/day/1000 persons in the following order: cocaine (528 ± 266), heroin (404 ± 315), methylphenidate (343 ± 396), amphetamine (308 ±105), ecstasy (MDMA; 114 ± 198), oxycodone (57 ± 28), methadone (58 ± 73), and codeine (84 ± 40). The consumption of oxycodone, methadone, heroin, and cocaine were identified as statistically lower in the Spring 2018 semester compared to the Fall 2017. Universities may need to increase drug education for the fall semester to lower the consumption of drugs in that semester. Data from this research encompasses both human health and the built environment by evaluating public health through collection of municipal wastewater, allowing public health officials rapid and robust narcotic consumption data while maintaining the anonymity of the students, faculty, and staff.
ContributorsCarlson, Alyssa Rose (Author) / Halden, Rolf (Thesis director) / Gushgari, Adam (Committee member) / School of Human Evolution & Social Change (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Over 5.8 million people are currently living with Alzheimer’s disease (AD), with the sixth highest mortality rate in the United States. No known cure or substantially life-extending treatment exists. With the growing aging population these numbers are only expected to increase to about 13.8 million by the year 2050. Alzheimer’s is a multifactorial disease, giving rise to two main types: familial AD (FAD) and sporadic AD (SAD). Although there are different factors associated with each type of the disease, both FAD and SAD result in neuronal and synaptic loss and remain difficult to model in-vitro and treat overall.
Current advances in cellular models of neurodegenerative diseases overcome a variety of limitations possessed in animal and post-mortem human models. Human-induced pluripotent stem cells (hiPSCs) provide a platform with cells that can self-renew and differentiate into mature and functional cell types. HiPSCs are at the forefront of neurodegenerative disease research because of their ability to differentiate into neural cell types. Apolipoprotein E (ApoE) is a protein encoded by the APOE gene found on chromosome 19 of the human genome. There are three common polymorphisms in the APOE gene, resulting from a single amino acid change in the protein. The presence of these polymorphisms are studied as associated risk factors of developing AD. Different combinations of these alleles closely relate to the risk a patient has in developing Alzheimer’s disease. The risk associated effects of this gene are primarily investigated, however the protective effects are not examined to the same extent.
This research aims to overcome the existing limitations in cell differentiations and improve cell population purity that limits the variables present in the culture. To do this, this study optimized a differentiation protocol by separating and purifying neuronal cell populations to study the potential protective effects associated with ApoE, a risk factor seen in SAD. This platform aims to use a purified cell population to effectively analyze cell type specific affects of the ApoE risk factor, specifically in neurons.
Current advances in cellular models of neurodegenerative diseases overcome a variety of limitations possessed in animal and post-mortem human models. Human-induced pluripotent stem cells (hiPSCs) provide a platform with cells that can self-renew and differentiate into mature and functional cell types. HiPSCs are at the forefront of neurodegenerative disease research because of their ability to differentiate into neural cell types. Apolipoprotein E (ApoE) is a protein encoded by the APOE gene found on chromosome 19 of the human genome. There are three common polymorphisms in the APOE gene, resulting from a single amino acid change in the protein. The presence of these polymorphisms are studied as associated risk factors of developing AD. Different combinations of these alleles closely relate to the risk a patient has in developing Alzheimer’s disease. The risk associated effects of this gene are primarily investigated, however the protective effects are not examined to the same extent.
This research aims to overcome the existing limitations in cell differentiations and improve cell population purity that limits the variables present in the culture. To do this, this study optimized a differentiation protocol by separating and purifying neuronal cell populations to study the potential protective effects associated with ApoE, a risk factor seen in SAD. This platform aims to use a purified cell population to effectively analyze cell type specific affects of the ApoE risk factor, specifically in neurons.
ContributorsFrisch, Carlye Arin (Author) / Brafman, David (Thesis director) / Tian, Xiaojun (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The combined use of methamphetamine and opioids has been reported to be on the rise throughout the United States (U.S.). However, our knowledge of this phenomenon is largely based upon reported overdoses and overdose-related deaths, law enforcement seizures, and drug treatment records; data that are often slow, restricted, and only track a portion of the population participating in drug consumption activities. As an alternative, wastewater-based epidemiology (WBE) has the capability to track licit and illicit drug trends within an entire community, at a low cost and in near real-time, while providing anonymity to those contributing to the sewer shed. In this study, wastewater was collected from two Midwestern U.S. cities (2017-2019) and analyzed for the prevalence of methamphetamine and the opioids oxycodone, codeine, fentanyl, tramadol, hydrocodone, and hydromorphone. Monthly 24-hour time-weighted composite samples (n = 48) from each city were analyzed using isotope dilution liquid chromatography tandem mass spectrometry. Results showed that methamphetamine and total opioid consumption (milligram morphine equivalents) in City 1 were strongly correlated only in 2017 (Spearman rank order correlation coefficient, ρ = 0.78), the relationship driven by fentanyl, hydrocodone, and hydromorphone. For City 2, methamphetamine and total opioid consumption were strongly positively correlated during the entire study (ρ = 0.54), with the correlations driven by hydrocodone and hydromorphone. In both cities, hydrocodone and hydromorphone mass loads were highly correlated, suggesting a parent and metabolite relationship. WBE provides important insights into licit and illicit drug consumption patterns in near real-time as they evolve; important information for community stakeholders in municipalities across the U.S.
ContributorsClick, Kathleen Grace (Author) / Halden, Rolf (Thesis director) / Gushgari, Adam (Committee member) / Driver, Erin (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Effectively modeling Alzheimer’s disease will lend to a more comprehensive
understanding of the disease pathology, more efficacious drug development and
regenerative medicine as a form of treatment. There are limitations with current
transgenic mouse models of Alzheimer’s disease and the study of post mortem brain tissue of Alzheimer’s diseases patients. Stem cell models can overcome the lack of clinical relevance and impracticality associated with current models. Ideally, the use of stem cell models provides the foundation to study the biochemical and physiological aspects of Alzheimer’s disease, but at the cellular level. Moreover, the future of drug development and disease modeling can be improved by developing a reproducible and well-characterized model of AD that can be scaled up to meet requirements for basic and translational applications. Characterization and analysis of a heterogenic neuronal culture developed from induced pluripotent stem cells calls for the understanding of single cell identity and cell viability. A method to analyze RNA following intracellular sorting was developed in order to analyze single cell identity of a heterogenic population
of human induced pluripotent stem cells and neural progenitor cells. The population was intracellularly stained and sorted for Oct4. RNA was isolated and analyzed with qPCR, which demonstrated expected expression profiles for Oct4+ and Oct4- cells. In addition, a protocol to label cells with pO2 sensing nanoprobes was developed to assess cell viability. Non-destructive nanoprobe up-take by neural progenitor cells was assessed with fluorescent imaging and flow cytometry. Nanoprobe labeled neurons were cultured long-term and continued to fluoresce at day 28. The proof of concept experiments demonstrated will be further expanded upon and utilized in developing a more clinically relevant and cost-effective model of Alzheimer’s disease with downstream applications
in drug development and regenerative medicine.
understanding of the disease pathology, more efficacious drug development and
regenerative medicine as a form of treatment. There are limitations with current
transgenic mouse models of Alzheimer’s disease and the study of post mortem brain tissue of Alzheimer’s diseases patients. Stem cell models can overcome the lack of clinical relevance and impracticality associated with current models. Ideally, the use of stem cell models provides the foundation to study the biochemical and physiological aspects of Alzheimer’s disease, but at the cellular level. Moreover, the future of drug development and disease modeling can be improved by developing a reproducible and well-characterized model of AD that can be scaled up to meet requirements for basic and translational applications. Characterization and analysis of a heterogenic neuronal culture developed from induced pluripotent stem cells calls for the understanding of single cell identity and cell viability. A method to analyze RNA following intracellular sorting was developed in order to analyze single cell identity of a heterogenic population
of human induced pluripotent stem cells and neural progenitor cells. The population was intracellularly stained and sorted for Oct4. RNA was isolated and analyzed with qPCR, which demonstrated expected expression profiles for Oct4+ and Oct4- cells. In addition, a protocol to label cells with pO2 sensing nanoprobes was developed to assess cell viability. Non-destructive nanoprobe up-take by neural progenitor cells was assessed with fluorescent imaging and flow cytometry. Nanoprobe labeled neurons were cultured long-term and continued to fluoresce at day 28. The proof of concept experiments demonstrated will be further expanded upon and utilized in developing a more clinically relevant and cost-effective model of Alzheimer’s disease with downstream applications
in drug development and regenerative medicine.
ContributorsKnittel, Jacob James (Author) / Brafman, David (Thesis director) / Salvatore, Oddo (Committee member) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05