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Description
Current methods for quantifying microplastics via LC-MS/MS analysis have been adapted from environmental monitoring protocols and are often inadequate for sampling within complex matrices. This study explores the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of microplastics. The initial phase of this research utilized pork kidney samples to establish a baseline for background and efficacy of sample processing. These findings underscore the complexity of developing a sensitive and specific analytical technique for microplastics in tissues. The observed discrepancies in contamination and replicability between samples emphasize the need for continual method optimization.
ContributorsBabbrah, Ayesha (Author) / Halden, Rolf (Thesis director) / Newell, Melanie (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-12
Description
This dissertation focused on studying risks associated with emerging drinking water contaminants and tradeoffs related to water management interventions. The built environment impacts health, as humans on average spend ~90% of their time indoors. Federal regulations generally focus on drinking water at the water treatment plant and within the distribution system as opposed to when it enters buildings after crossing the property line. If drinking water is not properly managed in buildings, it can be a source or amplifier of microbial and chemical contaminants. Unlike regulations for chemical contaminants that are risk-based, for pathogens, regulations are either based on recommended treatment technologies or designated as zero, which is not achievable in practice. Practice-based judgments are typically made at the building level to maintain water quality. This research focuses on two drinking water opportunistic pathogens of public health concern, Legionella pneumophila and Mycobacterium avium complex (MAC). Multiple aspects of drinking water quality in two green buildings were monitored in tandem with water management interventions. Additionally, a quantitative microbial risk assessment framework was used to predict risk-based critical concentrations of MAC for drinking water-related exposures in the indoor environment corresponding to a 1 in 10,000 annual infection target risk benchmark. The overall goal of this work was to inform the development of water management plans and guidelines for buildings that will improve water quality in the built environment and promote better public health. It was determined that a whole building water softening system with ion exchange softening resin and expansion tanks were unexplored reservoirs for the colonization of L. pneumophila. Furthermore, it was observed that typical water management interventions such as flushing and thermal disinfection did not always mitigate water quality issues. Thus, there was a need to implement several atypical interventions such as equipment replacement to improve the building water quality. This work has contributed comprehensive field studies and models that have highlighted the need for additional niches, facility management challenges, and risk tradeoffs for focus in water safety plans. The work also informs additional risk-based water quality policy approaches for reducing drinking water risks.
ContributorsJoshi, Sayalee (Author) / Hamilton, Kerry A (Thesis advisor) / Abbaszadegan, Morteza (Committee member) / Conroy-Ben, Otakuye (Committee member) / Halden, Rolf (Committee member) / Arizona State University (Publisher)
Created2023
Description
Synthetic plastics are ubiquitously used in a broad range of applications, including food and drink packaging. Plastics often contain chemical additives, including bisphenols, phthalates, and terephthalic acid, which can degrade under thermal stress. The environmental presence of these chemicals is cause for public concern, especially in consumer products that utilize plastic packaging, as many have been identified as endocrine disruptors. This study sought to determine exposure to phthalates, bisphenols, and terephthalic acid by quantifying a broad spectrum of these analytes within three bottled water brands at varying temperature exposure levels using the combination of solid phase extraction followed by isotope dilution liquid chromatography-tandem mass spectrometry. Monobenzyl phthalate was detected in two of the three brands after bottles were heated to ~100 °C, ranging from 98 – 107 ng/L, and bisphenol A was detected in one brand at ~100 °C at an average concentration of 748 ± 36 ng/L. Subsequent mass loading calculations demonstrated that bioaccumulation of BPA from Brand C after high levels of temperature exposure well exceeded the tolerable daily intake (TDI). Findings in this study indicate that consumers should not be expected to incur harmful exposures to the target compounds under normal conditions as analytes were not measured in water bottle samples at 25 °C or 60 °C. Further studies should explore a more nuisance approach to heating over long durations, including that of ultraviolet exposure.
ContributorsZevitz, Jacob (Author) / Halden, Rolf (Thesis director) / Driver, Erin (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2022-12
Description
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
Description
Monkeypox virus (MPXV) is an orthopoxvirus that causes smallpox-like disease and has up to a 10% mortality rate, depending on the infectious strain. The global eradication of the smallpox virus has led to the decrease in smallpox vaccinations, which has led to a drastic increase in the number of human MPXV cases. MPXV has been named the most important orthopoxvirus to infect humans since the eradication of smallpox and has been the causative agent of the 2022 world-wide MPXV outbreak. Despite being highly pathogenic, MPXV contains a natural truncation at the N-terminus of its E3 homologue. Vaccinia virus (VACV) E3 protein has two domains: an N- terminus Z-form nucleic acid binding domain (Z-BD) and a C-terminus double stranded RNA binding domain (dsRBD). Both domains are required for pathogenesis, interferon (IFN) resistance, and protein kinase R (PKR) inhibition. The N-terminus is required for evasion of Z-DNA binding protein 1 (ZBP1)-dependent necroptosis. ZBP1 binding to Z- form deoxyribonucleic acid/ribonucleic acid (Z-DNA/RNA) leads to activation of receptor-interacting protein kinase 3 (RIPK3) leading to mixed lineage kinase domain- like (MLKL) phosphorylation, aggregation and cell death. This study investigated how different cell lines combat MPXV infection and how MPXV has evolved ways to circumvent the host response. MPXV is shown to inhibit necroptosis in L929 cells by degrading RIPK3 through the viral inducer of RIPK3 degradation (vIRD) and by inhibiting MLKL aggregation. Additionally, the data shows that IFN treatment efficiently inhibits MPXV replication in a ZBP1-, RIPK3-, and MLKL- dependent manner, but independent of necroptosis. Also, the data suggests that an IFN inducer with a pancaspase or proteasome inhibitor could potentially be a beneficial treatment against MPXV infections. Furthermore, it reveals a link between PKR and pathogen-induced necroptosis that has not been previously described.
ContributorsWilliams, Jacqueline (Author) / Jacobs, Bertram (Thesis advisor) / Langland, Jeffrey (Committee member) / Lake, Douglas (Committee member) / Varsani, Arvind (Committee member) / Arizona State University (Publisher)
Created2022
Description
Traditional public health strategies for assessing human behavior, exposure, and activity are considered resource-exhaustive, time-consuming, and expensive, warranting a need for alternative methods to enhance data acquisition and subsequent interventions. This dissertation critically evaluated the use of wastewater-based epidemiology (WBE) as an inclusive and non-invasive tool for conducting near real-time population health assessments. A rigorous literature review was performed to gauge the current landscape of WBE to monitor for biomarkers indicative of diet, as well as exposure to estrogen-mimicking endocrine disrupting (EED) chemicals via route of ingestion. Wastewater-derived measurements of phytoestrogens from August 2017 through July 2019 (n = 156 samples) in a small sewer catchment revealed seasonal patterns, with highest average per capita consumption rates in January through March of each year (2018: 7.0 ± 2.0 mg d-1; 2019: 8.2 ± 2.3 mg d-1) and statistically significant differences (p = 0.01) between fall and winter (3.4 ± 1.2 vs. 6.1 ± 2.9 mg d-1; p ≤ 0.01) and spring and summer (5.6 ± 2.1 vs. 3.4 ± 1.5 mg d-1; p ≤ 0.01). Additional investigations, including a human gut microbial composition analysis of community wastewater, were performed to support a methodological framework for future implementation of WBE to assess population-level dietary behavior. In response to the COVID-19 global pandemic, a high-frequency, high-resolution sample collection approach with public data sharing was implemented throughout the City of Tempe, Arizona, and analyzed for SARS-CoV-2 (E gene) from April 2020 through March 2021 (n = 1,556 samples). Results indicate early warning capability during the first wave (June 2020) compared to newly reported clinical cases (8.5 ± 2.1 days), later transitioning to a slight lagging indicator in December/January 2020-21 (-2.0 ± 1.4 days). A viral hotspot from within a larger catchment area was detected, prompting targeted interventions to successfully mitigate community spread; reinforcing the importance of sample collection within the sewer infrastructure. I conclude that by working in tandem with traditional approaches, WBE can enlighten a comprehensive understanding of population health, with methods and strategies implemented in this work recommended for future expansion to produce timely, actionable data in support of public health.
ContributorsBowes, Devin Ashley (Author) / Halden, Rolf U (Thesis advisor) / Krajmalnik-Brown, Rosa (Thesis advisor) / Conroy-Ben, Otakuye (Committee member) / Varsani, Arvind (Committee member) / Whisner, Corrie (Committee member) / Arizona State University (Publisher)
Created2022
Description
Cities in the Global South face rapid urbanization challenges and often suffer an acute lack of infrastructure and governance capacities. Smart Cities Mission, in India, launched in 2015, aims to offer a novel approach for urban renewal of 100 cities following an area‐based development approach, where the use of ICT and digital technologies is particularly emphasized. This article presents a critical review of the design and implementation framework of this new urban renewal program across selected case‐study cities. The article examines the claims of the so‐called “smart cities” against actual urban transformation on‐ground and evaluates how “inclusive” and “sustainable” these developments are. We quantify the scale and coverage of the smart city urban renewal projects in the cities to highlight who the program includes and excludes. The article also presents a statistical analysis of the sectoral focus and budgetary allocations of the projects under the Smart Cities Mission to find an inherent bias in these smart city initiatives in terms of which types of development they promote and the ones it ignores. The findings indicate that a predominant emphasis on digital urban renewal of selected precincts and enclaves, branded as “smart cities,” leads to deepening social polarization and gentrification. The article offers crucial urban planning lessons for designing ICT‐driven urban renewal projects, while addressing critical questions around inclusion and sustainability in smart city ventures.`
ContributorsPraharaj, Sarbeswar (Author)
Created2021-05-07
Description
Poxviruses such as monkeypox virus (MPXV) are emerging zoonotic diseases. Compared to MPXV, Vaccinia virus (VACV) has reduced pathogenicity in humans and can be used as a partially protective vaccine against MPXV. While most orthopoxviruses have E3 protein homologues with highly similar N-termini, the MPXV homologue, F3, has a start codon mutation leading to an N-terminal truncation of 37 amino acids. The VACV protein E3 consists of a dsRNA binding domain in its C-terminus which must be intact for pathogenicity in murine models and replication in cultured cells. The N-terminus of E3 contains a Z-form nucleic acid (ZNA) binding domain and is also required for pathogenicity in murine models. Poxviruses produce RNA transcripts that extend beyond the transcribed gene which can form double-stranded RNA (dsRNA). The innate immune system easily recognizes dsRNA through proteins such as protein kinase R (PKR). After comparing a vaccinia virus with a wild-type E3 protein (VACV WT) to one with an E3 N-terminal truncation of 37 amino acids (VACV E3Δ37N), phenotypic differences appeared in several cell lines. In HeLa cells and certain murine embryonic fibroblasts (MEFs), dsRNA recognition pathways such as PKR become activated during VACV E3Δ37N infections, unlike VACV WT. However, MPXV does not activate PKR in HeLa or MEF cells. Additional investigation determined that MPXV produces less dsRNA than VACV. VACV E3Δ37N was made more similar to MPXV by selecting mutants that produce less dsRNA. By producing less dsRNA, VACV E3Δ37N no longer activated PKR in HeLa or MEF cells, thus restoring the wild-type phenotype. Furthermore, in other cell lines such as L929 (also a murine fibroblast) VACV E3Δ37N, but not VACV WT infection leads to activation of DNA-dependent activator of IFN-regulatory factors (DAI) and induction of necroptotic cell death. The same low dsRNA mutants demonstrate that DAI activation and necroptotic induction is independent of classical dsRNA. Finally, investigations of spread in an animal model and replication in cell lines where both the PKR and DAI pathways are intact determined that inhibition of both pathways is required for VACV E3Δ37N to replicate.
ContributorsCotsmire, Samantha (Author) / Jacobs, Bertram L (Thesis advisor) / Varsani, Arvind (Committee member) / Hogue, Brenda (Committee member) / Haydel, Shelley (Committee member) / Arizona State University (Publisher)
Created2021
Description
The production and incineration of single-use micropipette tips and disposable gloves, which are heavily used within laboratory facilities, generate large amounts of greenhouse gasses (GHGs) and accelerate climate change. Plastic waste that is not incinerated often is lost in the environment. The long degradation times associated with this waste exacerbates a variety of environmental problems such as substance runoff and ocean pollution. The objective of this study was to evaluate the efficacy of possible solutions for minimizing micropipette tip and disposable glove waste within laboratory spaces. It was hypothesized that simultaneously implementing the use of micropipette tip washers (MTWs) and energy-from-glove-waste programs (EGWs) would significantly reduce (p < 0.05) the average combined annual single-use plastic micropipette tip and nitrile glove waste (in kg) per square meter of laboratory space in the United States. ASU’s Biodesign Institute (BDI) was used as a case study to inform on the thousands of different laboratory facilities that exist all across the United States. Four separate research laboratories within the largest public university of the U.S. were sampled to assess the volume of plastic waste from single-use micropipette tips and gloves. Resultant data were used to represent the totality of single-use waste from the case study location and then extrapolated to all laboratory space in the United States. With the implementation of EGWs, annual BDI glove waste is reduced by 100% (0.47 ± 0.26 kg/m2; 35.5 ± 19.3 metric tons total) and annual BDI glove-related carbon emissions are reduced by ~5.01% (0.165 ± 0.09 kg/m2; 1.24 ± 0.68 metric tons total). With the implementation of MTWs, annual BDI micropipette tip waste is reduced by 92% (0.117 ± 0.03 kg/m2; 0.88 ± 0.25 metric tons total) and annual BDI tip-related carbon emissions are reduced by ~83.6% (4.04 ± 1.25 kg/m2; 30.5 ± 9.43 metric tons total). There was no significant difference (p = 0.06) observed between the mass of single-use waste (kg) in the sampled laboratory spaces before (x̄ = 47.1; σ = 43.3) and after (x̄ =0.070; σ = 0.033) the implementation of the solutions. When examining both solutions (MTWs & EGWs) implemented in conjunction with one another, the annual BDI financial savings (in regard to both purchasing and disposal costs) after the first year were determined to be ~$7.92 ± $9.31/m2 (7,500 m2 of total wet laboratory space) or ~$60,000 ± $70,000 total. These savings represent ~15.77% of annual BDI spending on micropipette tips and nitrile gloves. The large error margins in these financial estimates create high uncertainty for whether or not BDI would see net savings from implementing both solutions simultaneously. However, when examining the implementation of only MTWs, the annual BDI financial savings (in regard to both purchasing and disposal costs) after the first year were determined to be ~$12.01 ± $6.79 kg/m2 or ~$91,000 ± $51,200 total. These savings represent ~23.92% of annual BDI spending on micropipette tips and nitrile gloves. The lower error margins for this estimate create a much higher likelihood of net savings for BDI. Extrapolating to all laboratory space in the United States, the total annual amount of plastic waste avoided with the implementation of the MTWs was identified as 8,130 ± 2,290 tons or 0.023% of all solid plastic waste produced in the United States in 2018. The total amount of nitrile waste avoided with the implementation of the EGWs was identified as 32,800 ± 17,900 tons or 0.36% of all rubber solid waste produced in the United States in 2018. The total amount of carbon emissions avoided with the implementation of the MTWs was identified as 281,000 ± 87,000 tons CO2eq or 5.4*10-4 % of all CO2eq GHG emissions produced in the United States in 2020. Both the micropipette tip washer and the glove waste avoidance program solutions can be easily integrated into existing laboratories without compromising the integrity of the activities taking place. Implemented on larger scales, these solutions hold the potential for significant single-use waste reduction.
ContributorsZdrale, Gabriel (Author) / Mahant, Akhil (Co-author) / Halden, Rolf (Thesis director) / Biyani, Nivedita (Committee member) / Driver, Erin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05
Description
The production and incineration of single-use micropipette tips and disposable gloves, which are heavily used within laboratory facilities, generate large amounts of greenhouse gasses (GHGs) and accelerate climate change. Plastic waste that is not incinerated often is lost in the environment. The long degradation times associated with this waste exacerbates a variety of environmental problems such as substance runoff and ocean pollution. The objective of this study was to evaluate the efficacy of possible solutions for minimizing micropipette tip and disposable glove waste within laboratory spaces. It was hypothesized that simultaneously implementing the use of micropipette tip washers (MTWs) and energy-from-glove-waste programs (EGWs) would significantly reduce (p < 0.05) the average combined annual single-use plastic micropipette tip and nitrile glove waste (in kg) per square meter of laboratory space in the United States. ASU’s Biodesign Institute (BDI) was used as a case study to inform on the thousands of different laboratory facilities that exist all across the United States. Four separate research laboratories within the largest public university of the U.S. were sampled to assess the volume of plastic waste from single-use micropipette tips and gloves. Resultant data were used to represent the totality of single-use waste from the case study location and then extrapolated to all laboratory space in the United States. With the implementation of EGWs, annual BDI glove waste is reduced by 100% (0.47 ± 0.26 kg/m2; 35.5 ± 19.3 metric tons total) and annual BDI glove-related carbon emissions are reduced by ~5.01% (0.165 ± 0.09 kg/m2; 1.24 ± 0.68 metric tons total). With the implementation of MTWs, annual BDI micropipette tip waste is reduced by 92% (0.117 ± 0.03 kg/m2; 0.88 ± 0.25 metric tons total) and annual BDI tip-related carbon emissions are reduced by ~83.6% (4.04 ± 1.25 kg/m2; 30.5 ± 9.43 metric tons total). There was no significant difference (p = 0.06) observed between the mass of single-use waste (kg) in the sampled laboratory spaces before (x̄ = 47.1; σ = 43.3) and after (x̄ =0.070; σ = 0.033) the implementation of the solutions.When examining both solutions (MTWs & EGWs) implemented in conjunction with one another, the annual BDI financial savings (in regard to both purchasing and disposal costs) after the first year were determined to be ~$7.92 ± $9.31/m2 (7,500 m2 of total wet laboratory space) or ~$60,000 ± $70,000 total. These savings represent ~15.77% of annual BDI spending on micropipette tips and nitrile gloves. The large error margins in these financial estimates create high uncertainty for whether or not BDI would see net savings from implementing both solutions simultaneously. However, when examining the implementation of only MTWs, the annual BDI financial savings (in regard to both purchasing and disposal costs) after the first year were determined to be ~$12.01 ± $6.79 kg/m2 or ~$91,000 ± $51,200 total. These savings represent ~23.92% of annual BDI spending on micropipette tips and nitrile gloves. The lower error margins for this estimate create a much higher likelihood of net savings for BDI. Extrapolating to all laboratory space in the United States, the total annual amount of plastic waste avoided with the implementation of the MTWs was identified as 8,130 ± 2,290 tons or 0.023% of all solid plastic waste produced in the United States in 2018. The total amount of nitrile waste avoided with the implementation of the EGWs was identified as 32,800 ± 17,900 tons or 0.36% of all rubber solid waste produced in the United States in 2018. The total amount of carbon emissions avoided with the implementation of the MTWs was identified as 281,000 ± 87,000 tons CO2eq or 5.4*10-4 % of all CO2eq GHG emissions produced in the United States in 2020. Both the micropipette tip washer and the glove waste avoidance program solutions can be easily integrated into existing laboratories without compromising the integrity of the activities taking place. Implemented on larger scales, these solutions hold the potential for significant single-use waste reduction.
ContributorsMahant, Akhil (Author) / Zdrale, Gabriel (Co-author) / Halden, Rolf (Thesis director) / Biyani, Nivedita (Committee member) / Driver, Erin (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2022-05