Matching Items (211)
Description
Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including high false positive rates, low throughput, and lack of quantification. Moreover, most methods are not compatible for use in a clinical setting. To address these limitations, we have developed a multiplexed, in-solution protein microarray (MISPA) platform with broad applications in proteomics. MISPA can be used to quantitatively profile PPIs and as a robust technology for early detection of cancers. This method utilizes unique DNA barcoding of individual proteins coupled with next generation sequencing to quantitatively assess interactions via barcode enrichment. We have tested the feasibility of this technology in the detection of patient immune responses to oropharyngeal carcinomas and in the discovery of novel PPIs in the B-cell receptor (BCR) pathway. To achieve this goal, 96 human papillomavirus (HPV) antigen genes were cloned into pJFT7-cHalo (99% success) and pJFT7-n3xFlag-Halo (100% success) expression vectors. These libraries were expressed via a cell-free in vitro transcription-translation system with 93% and 96% success, respectively. A small-scale study of patient serum interactions with barcoded HPV16 antigens was performed and a HPV proteome-wide study will follow using additional patient samples. In addition, 15 query proteins were cloned into pJFT7_nGST expression vectors, expressed, and purified with 93% success to probe a library of 100 BCR pathway proteins and detect novel PPIs.
ContributorsRinaldi, Capria Lakshmi (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Solar energy has become one of the most popular renewable energy in human’s life because of its abundance and environment friendliness. To achieve high solar energy conversion efficiency, it usually requires surfaces to absorb selectivity within one spectral range of interest and reflect strongly over the rest of the spectrum. An economic method is always desired to fabricate spectrally selective surfaces with improved energy conversion efficiency. Colloidal lithography is a recently emerged way of nanofabrication, which has advantages of low-cost and easy operation.
In this thesis, aluminum metasurface structures are proposed based on colloidal lithography method. High Frequency Structure Simulator is used to numerically study optical properties and design the aluminum metasurfaces with selective absorption. Simulation results show that proposed aluminum metasurface structure on aluminum oxide thin film and aluminum substrate has a major reflectance dip, whose wavelength is tunable within the near-infrared and visible spectrum with metasurface size. As the metasurface is opaque due to aluminum film, it indicates strong wavelength-selective optical absorption, which is due to the magnetic resonance between the top metasurface and bottom Al film within the aluminum oxide layer.
The proposed sample is fabricated based on colloidal lithography method. Monolayer polystyrene particles of 500 nm are successfully prepared and transferred onto silicon substrate. Scanning electron microscope is used to check the surface topography. Aluminum thin film with 20-nm or 50-nm thickness is then deposited on the sample. After monolayer particles are removed, optical properties of samples are measured by micro-scale optical reflectance and transmittance microscope. Measured and simulated reflectance of these samples do not have frequency selective properties and is not sensitive to defects. The next step is to fabricate the Al metasurface on Al_2 O_3 and Al films to experimentally demonstrate the selective absorption predicted from the numerical simulation.
In this thesis, aluminum metasurface structures are proposed based on colloidal lithography method. High Frequency Structure Simulator is used to numerically study optical properties and design the aluminum metasurfaces with selective absorption. Simulation results show that proposed aluminum metasurface structure on aluminum oxide thin film and aluminum substrate has a major reflectance dip, whose wavelength is tunable within the near-infrared and visible spectrum with metasurface size. As the metasurface is opaque due to aluminum film, it indicates strong wavelength-selective optical absorption, which is due to the magnetic resonance between the top metasurface and bottom Al film within the aluminum oxide layer.
The proposed sample is fabricated based on colloidal lithography method. Monolayer polystyrene particles of 500 nm are successfully prepared and transferred onto silicon substrate. Scanning electron microscope is used to check the surface topography. Aluminum thin film with 20-nm or 50-nm thickness is then deposited on the sample. After monolayer particles are removed, optical properties of samples are measured by micro-scale optical reflectance and transmittance microscope. Measured and simulated reflectance of these samples do not have frequency selective properties and is not sensitive to defects. The next step is to fabricate the Al metasurface on Al_2 O_3 and Al films to experimentally demonstrate the selective absorption predicted from the numerical simulation.
ContributorsGuan, Chuyun (Author) / Wang, Liping (Thesis advisor) / Azeredo, Bruno (Committee member) / Wang, Robert (Committee member) / Arizona State University (Publisher)
Created2019
Description
Meditation app usage is associated with decreases in stress, anxiety, and depression symptoms. Many meditation app subscribers, however, quickly abandon or reduce their app usage. This dissertation presents three manuscripts which 1) determined the behavioral, demographic, and socioeconomic factors associated with the abandonment of a meditation app, Calm, during the COVID-19 pandemic, 2) determined which participant characteristics predicted meditation app usage in the first eight weeks after subscribing, and 3) determined if changes in stress, anxiety, and depressive symptoms from baseline to Week 8 predicted meditation app usage from Weeks 8-16. In Manuscript 1, a survey was distributed to Calm subscribers in March 2020 that assessed meditation app behavior and meditation habit strength, and demographic information. Cox proportional hazards regression models were estimated to assess time to app abandonment. In Manuscript 2, new Calm subscribers completed a baseline survey on participants’ demographic and baseline mental health information and app usage data were collected over 8 weeks. In Manuscript 3, new Calm subscribers completed a baseline and Week 8 survey on demographic and mental health information. App usage data were collected over 16 weeks. Regression models were used to assess app usage for Manuscripts 2 and 3. Findings from Manuscript 1 suggest meditating after an existing routine decreased risk of app abandonment for pre-pandemic subscribers and for pandemic subscribers. Additionally, meditating “whenever I can” decreased risk of abandonment among pandemic subscribers. No behavioral factors were significant predictors of app abandonment among the long-term subscribers. Findings from Manuscript 2 suggest men had more days of meditation than women. Mental health diagnosis increased average daily meditation minutes. Intrinsic motivation for meditation increased the likelihood of completing any meditation session, more days with meditation sessions, and more average daily meditation minutes. Findings from Manuscript 3 suggest improvements in stress increased average daily meditation minutes. Improvements in depressive symptoms decreased daily meditation minutes. Evidence from this three-manuscript dissertation suggests meditation cue, time of day, motivation, symptom changes, and demographic and socioeconomic variables may be used to predict meditation app usage.
ContributorsSullivan, Mariah (Author) / Stecher, Chad (Thesis advisor) / Huberty, Jennifer (Committee member) / Buman, Matthew (Committee member) / Larkey, Linda (Committee member) / Chung, Yunro (Committee member) / Arizona State University (Publisher)
Created2022
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
Young adult collegiate women, particularly students with adverse childhood experiences (ACEs) and who have experienced intimate partner violence (IPV) victimization, report a myriad of adverse mental health and academic difficulties. Practicing yoga has demonstrated promising findings among adults as a healing modality in the aftermath of interpersonal violence victimization and traumatization. Less known are the associations between collegiate women’s yoga participation and their mental health, body connection, and academic well-being examined through a yoga feminist- trauma conceptual framework. Among young adult collegiate women, this study examined (1) associations amongst socio-demographics, mental health service use, IPV types, and yoga participation (2) the strength and direction of associations on measures of ACEs, mental health, body connection, and academic well-being, (3) whether yoga participation predicted students’ mental health, body connection, and academic well-being after controlling for confounding variables, including ACEs and IPV victimization, and (4) whether socio-demographics, mental health service use, ACEs, and IPV types predicted yoga participation. This study was observational, cross-sectional, and gathered self-report quantitative data. Eligible participants were current collegiate women enrolled at an urban, public university in the southwestern United States who were 18 to 24 years of age. The main sub-sample (n = 93) included students who were ever in an intimate relationship and practiced yoga within the past year. IRB approval was obtained. Findings demonstrated that yoga participation was not a significant predictor of students’ mental health, body connection, or academic well-being. Socio-demographics, mental health service use, ACEs, and IPV did not predict yoga participation. However, women with greater ACEs fared worse on measures of mental health (i.e., depression and post-traumatic stress disorder symptoms), and women with experiences of IPV harassment reported greater post-traumatic stress disorder symptoms. Further, employed women reported fewer depression symptoms and were less likely to experience emotional IPV. Lastly, students with greater body connection (more awareness) fared better academically. This research supports prior literature on the adverse mental health outcomes among young adult collegiate women with histories of interpersonal violence. Further examination is warranted into employment and body connection, particularly related to yoga, as protective factors of students' health, safety, and academic well-being.
ContributorsKappas Mazzio, Andrea Alexa (Author) / Messing, Jill T (Thesis advisor) / Mendoza, Natasha (Committee member) / Huberty, Jennifer (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