Matching Items (194)
Description
Biogas’s potential as a renewable fuel source has been an area of increased research in recent years. One issue preventing wide-spread use of biogas as a fuel is the trace amounts of impurities that damage fuel-burning equipment by depositing silicon, sulfur, calcium and other elements on their surface. This study aims to analyze the effects of a high concentration of L4 linear siloxane on solid oxide fuel cell performance until failure occurs. L4 siloxane has not been extensively researched previously, and this investigation aims to provide new data to support similar, though slower, degradation compared to D4, D5 and other siloxanes in solid oxide fuel cells. The experiments were conducted inside a furnace heated to 800℃ with an Ni-YSZ-supported (Nickel-yttria-stabilized zirconia) fuel cell. A fuel source with a flow rate of 20 mL/min of hydrogen gas, 10 mL/min of nitrogen gas and 0.15 mL/min of L4 siloxane was used. Air was supplied to the cathode. The effects of siloxane deposition on cell voltage and power density degradation and resistance increase were studied by using techniques like the current-voltage method, electrochemical impedance spectroscopy, and gas chromatography. The results of the experiment after reduction show roughly constant degradation of 8.35 mV/hr, followed after approximately 8 hours by an increasing degradation until cell failure of 130.45 mV/hr. The initial degradation and stagnation match previous research in siloxane deposition on SOFCs, but the sharp decline to failure does not. A mechanism for solid oxide fuel cell failure is proposed based on the data.
ContributorsRiley, Derall M. (Author) / Milcarek, Ryan J (Thesis advisor) / Wang, Liping (Committee member) / Phelan, Patrick E (Committee member) / Arizona State University (Publisher)
Created2021
Description
The TP53 tumor suppressor gene is the most frequently mutated gene in human cancers. In the highly aggressive triple negative breast cancer (TNBC), TP53 is mutated in 80% of cases. TNBC lacks viable drug targets, resulting in a low prognosis (12.2% 5 year survivability rate). As such, the discovery of druggable targets in TNBC would be beneficial. Mutated p53 protein typically occurs as a missense mutation and often endows cancer cells with gain of function (GOF) properties by dysregulating metabolic pathways. One of these frequently dysregulated pathways is the Hippo/Yes-associated protein-1 (YAP1)/WW Domain Containing Transcription Regulator 1 (TAZ) tumor suppressor pathway. This study therefore analyzed the involvement of the Hippo/YAP1/TAZ pathway in p53-mediated breast cancer cell invasion. From an RNA-seq screen in MCF10A cell lines harboring different TP53 missense mutations, each with a differing invasive phenotype, components of the Hippo pathway were found to correlate with cell invasion. To this end, the active and inactive forms of YAP1 and TAZ were studied. Phosphorylated (inactive) YAP1 and TAZ are retained in the cytoplasm and eventually degraded. Unphosphorylated (active) YAP1 and TAZ translocate to the nucleus to activate TEAD-family transcription factors, inducing cell survival and proliferation genes leading to increased cell invasion. Using quantitative western blot analysis, it was found that inactive TAZ expression was lower in the most invasive cell lines and higher in the least invasive cell lines (p = 0.003). Moreover, the ratio of inactive TAZ protein to total TAZ protein was also shown to be predominantly lower in the invasive cell lines compared to the non-invasive lines (p = 0.04). Finally, active TAZ expression was primarily higher in p53-mutant invasive cell lines and lower in non-invasive p53 mutant cells. Additionally, although YAP1 and TAZ are thought to be functionally redundant, the pattern seen in TAZ was not seen in the YAP1 protein. Taken together, the results demonstrated here suggest that TAZ holds a more dominant role in governing TNBC cell invasion compared to YAP1 and further highlights TAZ as a potential therapeutic target in TNBC.
ContributorsGrief, Dustin (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Glioblastoma (GBM), the most common and aggressive primary brain tumor affecting adults, is characterized by an aberrant yet druggable epigenetic landscape. The Histone Deacetylases (HDACs), a major family of epigenetic regulators, favor transcriptional repression by mediating chromatin compaction and are frequently overexpressed in human cancers, including GBM. Hence, over the last decade there has been considerable interest in using HDAC inhibitors (HDACi) for the treatment of malignant primary brain tumors. However, to date most HDACi tested in clinical trials have failed to provide significant therapeutic benefit to patients with GBM. This is because current HDACi have poor or unknown pharmacokinetic profiles, lack selectivity towards the different HDAC isoforms, and have narrow therapeutic windows. Isoform selectivity for HDACi is important given that broad inhibition of all HDACs results in widespread toxicity across different organs. Moreover, the functional roles of individual HDAC isoforms in GBM are still not well understood. Here, I demonstrate that HDAC1 expression increases with brain tumor grade and is correlated with decreased survival in GBM. I find that HDAC1 is the essential HDAC isoform in glioma stem cells and its loss is not compensated for by its paralogue HDAC2 or other members of the HDAC family. Loss of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner and leads to significant suppression of tumor growth in vivo. While no HDAC isoform-selective inhibitors are currently available, the second-generation HDACi quisinostat harbors high specificity for HDAC1. I show that quisinostat exhibits potent growth inhibition in multiple patient-derived glioma stem cells. Using a pharmacokinetics- and pharmacodynamics-driven approach, I demonstrate that quisinostat is a brain-penetrant molecule that reduces tumor burden in flank and orthotopic models of GBM and significantly extends survival both alone and in combination with radiotherapy. The work presented in this thesis thereby unveils the non-redundant functions of HDAC1 in therapy- resistant glioma stem cells and identifies a brain-penetrant HDACi with higher selectivity towards HDAC1 as a potent radiosensitizer in preclinical models of GBM. Together, these results provide a rationale for developing quisinostat as a potential adjuvant therapy for the treatment of GBM.
ContributorsLo Cascio, Costanza (Author) / LaBaer, Joshua (Thesis advisor) / Mehta, Shwetal (Committee member) / Mirzadeh, Zaman (Committee member) / Mangone, Marco (Committee member) / Paek, Andrew (Committee member) / Arizona State University (Publisher)
Created2022
Description
The thermal conductivity of cadmium sulfide (CdS) colloidal nanocrystals (NCs) and magic-sized clusters (MSCs) have been investigated in this work. It is well documented in the literature that the thermal conductivity of colloidal nanocrystal assemblies decreases as diameter decreases. However, the extrapolation of this size dependence does not apply to magic-sized clusters. Magic-sized clusters have an anomalously high thermal conductivity relative to the extrapolated size-dependence trend line for the colloidal nanocrystals. This anomalously high thermal conductivity could probably result from the monodispersity of magic-sized clusters. To support this conjecture, a method of deliberately eliminating the monodispersity of MSCs by mixing them with colloidal nanocrystals was performed. Experiment results showed that mixtures of nanocrystals and MSCs have a lower thermal conductivity that falls approximately on the extrapolated trendline for colloidal nanocrystal thermal conductivity as a function of size.
ContributorsSun, Ming-Hsien (Author) / Wang, Robert (Thesis advisor) / Rykaczewski, Konrad (Committee member) / Wang, Liping (Committee member) / Arizona State University (Publisher)
Created2022
Description
Windows are one of the most significant locations of heat transfer through a building envelope. In warm climates, it is important that heat gain through windows is minimized. Heat transfer through a window glazing occurs by all major forms of heat transfer (convection, conduction, and radiation). Convection and conduction effects can be limited by manipulating the thermal properties of a window’s construction. However, radiation heat transfer into a building will always occur if a window glazing is visibly transparent. In an effort to reduce heat gain through the building envelope, a window glazing can be designed with spectrally selective properties. These spectrally selective glazings would possess high reflectivity in the near-infrared (NIR) regime (to prevent solar heat gain) and high emissivity in the atmospheric window, 8-13μm (to take advantage of the radiative sky cooling effect). The objective of this thesis is to provide a comprehensive study of the thermal performance of a visibly transparent, high-emissivity glass window. This research proposes a window constructed by coating soda lime glass in a dual layer consisting of Indium Tin Oxide (ITO) and Polyvinyl Fluoride (PVF) film. The optical properties of this experimental glazing were measured and demonstrated high reflectivity in the NIR regime and high emissivity in the atmospheric window. Outdoor field tests were performed to experimentally evaluate the glazing’s thermal performance. The thermal performance was assessed by utilizing an experimental setup intended to mimic a building with a skylight. The proposed glazing experimentally demonstrated reduced indoor air temperatures compared to bare glass, ITO coated glass, and PVF coated glass. A theoretical heat transfer model was developed to validate the experimental results. The results of the theoretical and experimental models showed good agreement. On average, the theoretical model demonstrated 0.44% percent error during the daytime and 0.52% percent error during the nighttime when compared to the experimentally measured temperature values.
ContributorsTrujillo, Antonio Jose (Author) / Phelan, Patrick (Thesis advisor) / Wang, Liping (Thesis advisor) / Rykaczewski, Konrad (Committee member) / Arizona State University (Publisher)
Created2022
Description
The objective of this dissertation is to study the optical and radiative properties of inhomogeneous metallic structures. In the ongoing search for new materials with tunable optical characteristics, porous metals and nanowires provides an extensive design space to engineer its optical response based on the morphology-dependent phenomena.This dissertation firstly discusses the use of aluminum nanopillar array on a quartz substrate as spectrally selective optical filter with narrowband transmission for thermophotovoltaic systems. The narrow-band transmission enhancement is attributed to the magnetic polariton resonance between neighboring aluminum nanopillars. Tuning of the resonance wavelengths for selective filters was achieved by changing the nanopillar geometry. It concludes by showing improved efficiency of Gallium-Antimonide thermophotovoltaic system by coupling the designed filter with the cell.
Next, isotropic nanoporous gold films are investigated for applications in energy conversion and three-dimensional laser printing. The fabricated nanoporous gold samples are characterized by scanning electron microscopy, and the spectral hemispherical reflectance is measured with an integrating sphere. The effective isotropic optical constants of nanoporous gold with varying pore volume fraction are modeled using the Bruggeman effective medium theory.
Nanoporous gold are metastable and to understand its temperature dependent optical properties, a lab-scale fiber-based optical spectrometer setup is developed to characterize the in-situ specular reflectance of nanoporous gold thin films at temperatures ranging from 25 to 500 oC. The in-situ and the ex-situ measurements suggest that the
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specular, diffuse, and hemispherical reflectance varies as a function of temperature due to the morphology (ligament diameter) change observed.
The dissertation continues with modeling and measurements of the radiative properties of porous powders. The study shows the enhanced absorption by mixing porous copper to copper powder. This is important from the viewpoint of scalability to get end products such as sheets and tubes with the requirement of high absorptance that can be produced through three-dimensional printing.
Finally, the dissertation concludes with recommendations on the methods to fabricate the suggested optical filters to improve thermophotovoltaic system efficiencies. The results presented in this dissertation will facilitate not only the manufacturing of materials but also the promising applications in solar thermal energy and optical systems.
ContributorsRamesh, Rajagopalan (Author) / Wang, Liping (Thesis advisor) / Azeredo, Bruno (Thesis advisor) / Phelan, Patrick (Committee member) / Yu, Hongbin (Committee member) / Rykaczewski, Konrad (Committee member) / Arizona State University (Publisher)
Created2022
Description
Transient Receptor Potential Vanilloid-1 (TRPV1) is an integral membrane polymodal cation channel involved in various essential biological functions, including thermosensing, thermoregulation, and nociception. Discrete TRPV1 activation modes such as ligand, heat, and proton have been challenging to disentangle. However, dissecting the polymodal nature of TRPV1 is essential for therapeutic development. The human TRPV1 (hTRPV1) voltage-sensing like domain (VSLD; transmembrane helices S1-S4) contains the canonical vanilloid ligand binding site and significantly contributes to thermosensing. Nuclear magnetic resonance (NMR)-detected studies probe the role of the hTRPV1-VSLD in TRPV1 polymodal function. The hTRPV1-VSLD is identified as an allosteric hub for all three primary TRPV1 activation modes and demonstrates plasticity in chemical ligand modulation. The presented results underscore molecular features in the VSLD that dictate TRPV1 function, highlighting important considerations for future therapeutic design.
ContributorsOwens, Aerial M. (Author) / Van Horn, Wade D. (Thesis advisor) / Levitus, Marcia (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2023
Description
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, declared in March 2020 resulted in an unprecedented scientific effort that led to the deployment in less than a year of several vaccines to prevent severe disease, hospitalizations, and death from coronavirus disease 2019 (COVID-19). Most vaccine models focus on the production of neutralizing antibodies against the spike (S) to prevent infection. As the virus evolves, new variants emerge that evade neutralizing antibodies produced by natural infection and vaccination, while memory T cell responses are long-lasting and resilient to most of the changes found in variants of concern (VOC). Several lines of evidence support the study of T cell-mediated immunity in SARS-CoV-2 infections. First, T cell reactivity against SARS-CoV-2 is found in both (cluster of differentiation) CD4+ and CD8+ T cell compartments in asymptomatic, mild, and severe recovered COVID-19 patients. Second, an early and stronger CD8+ T cell response correlates with less severe COVID-19 disease [1-4]. Third, both CD4+ and CD8+ T cells that are reactive to SARS-CoV-2 viral antigens are found in healthy unexposed individuals suggesting that cross-reactive and conserved epitopes may be protective against infection.
The current study is focused on the T cell-mediated response, with special attention to conserved, non-spike-cross-reactive epitopes that may be protective against SARS-CoV-2. The first chapter reviews the importance of epitope prediction in understanding the T cell-mediated responses to a pathogen. The second chapter centers on the validation of SARS-CoV-2 CD8+ T cell predicted peptides to find conserved, immunodominant, and immunoprevalent epitopes that can be incorporated into the next generation of vaccines against severe COVID-19 disease. The third chapter explores pre-existing immunity to SARS-CoV-2 in a pre-pandemic cohort and finds two highly immunogenic epitopes that are conserved among human common cold coronaviruses (HCoVs). To end, the fourth chapter explores the concept of T cell receptor (TCR) cross-reactivity by isolating SARS-CoV-2-reactive TCRs to elucidate the mechanisms of cross-reactivity to SARS-CoV-2 and other human coronaviruses (HCoVs).
ContributorsCarmona, Jacqueline (Author) / Anderson, Karen S (Thesis advisor) / Lake, Douglas (Thesis advisor) / Maley, Carlo (Committee member) / Mangone, Marco (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2023
Description
Energy storage technologies are essential to overcome the temporal variability in renewable energy. The primary aim of this thesis is to develop reactor solutions to better analyze the potential of thermochemical energy storage (TCES) using non-stoichiometric metal oxides, for the multi-day energy storage application. A TCES system consists of a reduction reactor and an insulated MOx storage bin. The reduction reactor heats (to ~ 1100 °C) and partially reduces the MOx, thereby adding sensible and chemical energy (i.e., charging it) under reduced pO2 environments (~10 Pa). Inert gas removes the oxygen generated during reduction. The storage bin holds the hot and partially reduced MOx (typically particles) until it is used in an energy recovery device (i.e., discharge). Irrespective of the reactor heat source (here electrical), or the particle-inert gas flows (here countercurrent), the thermal reduction temperature and inert gas (here N2) flow minimize when the process approaches reversibility, i.e., operates near equilibrium. This study specifically focuses on developing a reduction reactor based on the theoretical considerations for approaching reversibility along the reaction path. The proposed Zigzag flow reactor (ZFR) is capable of thermally reducing CAM28 particles at temperatures ~ 1000 °C under an O2 partial pressure ~ 10 Pa. The associated analytical and numerical models analyze the reaction equilibrium under a real (discrete) reaction path and the mass transfer kinetic conditions necessary to approach equilibrium. The discrete equilibrium model minimizes the exergy destroyed in a practical reactor and identifies methods of maximizing the energy storage density () and the exergetic efficiency. The mass transfer model analyzes the O2 N2 concentration boundary layers to recommend sizing considerations to maximize the reactor power density. Two functional ZFR prototypes, the -ZFR and the -ZFR, establish the proof of concept and achieved a reduction extent, Δδ = 0.071 with CAM28 at T~950 °C and pO2 = 10 Pa, 7x higher than a previous attempt in the literature. The -ZFR consistently achieved > 100 Wh/kg during >10 h. runtime and the -ZFR displayed an improved = 130 Wh/kg during >5 h. operation with CAM28. A techno-economic model of a grid-scale ZFR with an associated storage bin analyzes the cost of scaling the ZFR for grid energy storage requirements. The scaled ZFR capital costs contribute < 1% to the levelized cost of thermochemical energy storage, which ranges from 5-20 ¢/kWh depending on the storage temperature and storage duration.
ContributorsGhotkar, Rhushikesh (Author) / Milcarek, Ryan (Thesis advisor) / Ermanoski, Ivan (Committee member) / Phelan, Patrick (Committee member) / Wang, Liping (Committee member) / Wang, Robert (Committee member) / Arizona State University (Publisher)
Created2023
Description
Redox homeostasis is described as the net physiologic balance between inter-convertible oxidized and reduced equivalents within subcellular compartments that remain in a dynamic equilibrium. This equilibrium is impacted by reactive oxygen species (ROS), which are natural by-products of normal cellular activity. Studies have shown that cancer cells have high ROS levels and altered redox homeostasis due to increased basal metabolic activity, mitochondrial dysfunction, peroxisome activity, as well as the enhanced activity of NADPH oxidase, cyclooxygenases, and lipoxygenases. Glioblastoma (GBM) is the most prevalent primary brain tumor in adults with a median survival of 15 months. GBM is characterized by its extreme resistance to therapeutic interventions as well as an elevated metabolic rate that results in the exacerbated production of ROS. Therefore, many agents with either antioxidant or pro-oxidant mechanisms of action have been rigorously employed in preclinical as well as clinical settings for treating GBM by inducing oxidative stress within the tumor. Among those agents are well-known antioxidant vitamin C and small molecular weight SOD mimic BMX-001, both of which are presently in clinical trials on GBM patients. Despite the wealth of investigations, limited data is available on the response of normal brain vs glioblastoma tissue to these therapeutic interventions. Currently, a sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the quantification of a panel of oxidative stress biomarkers: glutathione (GSH), cysteine (Cys), glutathione disulfide (GSSG), and cysteine disulfide in human-derived brain tumor and mouse brain samples; this method will be enriched with additional oxidative stress biomarkers homocysteine (Hcy), methionine (Met), and cystathionine (Cyst). Using this enriched method, we propose to evaluate the thiol homeostasis and the redox state of both normal brain and GBM in mice after exposure with redox-active therapeutics. Our results showed that, compared to normal brain (in intact mice), GBM tissue has significantly lower GSH/GSSG and Cys/CySS ratios indicating much higher oxidative stress levels. Contralateral “normal” brain tissue collected from the mice with intracranial GBM were also under significant oxidative stress compared to normal brains collected from the intact mice. Importantly, normal brain tissue in both studies retained the ability to restore redox homeostasis after treatment with a redox-active therapeutic within 24 hours while glioblastoma tissue does not. Ultimately, elucidating the differential redox response of normal vs tumor tissue will allow for the development of more redox-active agents with therapeutic benefit.
ContributorsShaik, Kamal (Author) / LaBaer, Joshua (Thesis director) / Tovmasyan, Artak (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2022-12