Matching Items (72)
Description
A genome wide association study (GWAS) of treatment outcomes for citalopram and escitalopram, two frontline SSRI treatments for Major Depressive Disorder, was conducted with 529 subjects on an imputed dataset. While no variants of genome-wide significance were identified, various potentially interesting variants were identified that warrant further exploration. These findings

A genome wide association study (GWAS) of treatment outcomes for citalopram and escitalopram, two frontline SSRI treatments for Major Depressive Disorder, was conducted with 529 subjects on an imputed dataset. While no variants of genome-wide significance were identified, various potentially interesting variants were identified that warrant further exploration. These findings have the potential to elucidate novel mechanisms underlying drug response for SSRIs. This work will be continued further, with machine learning and deep learning analyses to perform non-linear analyses and employing a biologist or geneticist to provide more specialized knowledge for interpretation of results.
ContributorsLeiter-Weintraub, Ethan (Author) / Dinu, Valentin (Thesis director) / Scotch, Matthew (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / College of Health Solutions (Contributor) / School of Life Sciences (Contributor)
Created2024-05
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Description
The silicon-based solar cell has been extensively deployed in photovoltaic industry and plays an important role in renewable energy industries. A more energy-efficient, environment-harmless and eco-friendly silicon production technique is required for price-competitive solar energy harvesting. Silicon electrorefining in molten salt is promising for the ultrapure solar-grade Si production. To

The silicon-based solar cell has been extensively deployed in photovoltaic industry and plays an important role in renewable energy industries. A more energy-efficient, environment-harmless and eco-friendly silicon production technique is required for price-competitive solar energy harvesting. Silicon electrorefining in molten salt is promising for the ultrapure solar-grade Si production. To avoid using highly corrosive fluoride salt, CaCl2-based salt is widely employed for silicon electroreduction. For Si electroreduction in CaCl2-based salt, CaO is usually added to enhance the solubility of SiO2. However, the existence of oxygen in molten salt could result in system corrosion, anode passivation and the co-deposition of secondary phases such as CaSiO3 and SiO2 at the cathode. This research focuses on the development of reusable oxygen-free CaCl2-based molten salt for solar-grade silicon electrorefining. A new multi-potential electropurification process has been proposed and proven to be more effective in impurities removal. The as-received salt and the salt after electrorefining have been electropurified. The inductively-coupled plasma mass spectrometry and cyclic voltammetry have been utilized to determine the impurities removal of electropurification. The salt after silicon electrorefining has been regenerated to its original purity level before by the multi-potential electropurification process, demonstrating the feasibility of a reusable salt by electropurification. In an oxygen-free CaCl2-based salt without silicon precursor, the silicon dissolved from the silicon anode can be successfully deposited at the cathode. The silicon anode has been operated for more than 50 hours without passivation in the oxygen-free system. Silicon ions start to be deposited after 0.17 g of silicon has been dissolved into the salt from the silicon anode. A 180 µm deposit with a silver-luster surface was obtained at the cathode. The main impurities in the silicon anode such as aluminum, iron and titanium were not found in the silicon deposits. No oxygen-containing secondary phases are detected in the silicon deposits. These results confirm the feasibility of silicon electrorefining in the oxygen-free CaCl2-based salt.
ContributorsTseng, Mao-Feng (Author) / Tao, Meng (Thesis advisor) / Kannan, Arunachala Mada (Committee member) / Mu, Linqin (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2023
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Description

The current Solid-State Electrolyte (SSE) used in Li-ion batteries are limited by their current production methods (i.e., die-pressing; tape casting), planar geometries and random porosities. This constrains their use for mass production in manufacturing plants. 3D-printing of SSEs, however, is a new, highly-researched method that shows promise in expanding beyond

The current Solid-State Electrolyte (SSE) used in Li-ion batteries are limited by their current production methods (i.e., die-pressing; tape casting), planar geometries and random porosities. This constrains their use for mass production in manufacturing plants. 3D-printing of SSEs, however, is a new, highly-researched method that shows promise in expanding beyond the laboratory to more large-scale industrial production as rapid prototyping takes place. Indeed, laboratory studies to date suggest that SSE technology is safer than current production methods and provides a safe high energy solid-state battery. For SSE technology to become a reality though, it must be scalable and financially feasible. Therefore, this thesis aids to bridge the gap between laboratory studies and commercialization by examining the financial feasibility of adopting this technology for a hypothetical battery manufacturing plant. In doing this, I develop a model of the incremental net cash flows, and subsequently the Net Present Value (NPV), from such an enterprise. If the present value of future cash flows from the enterprise are anticipated to be greater than the investment costs, the NPV is positive and the investment in this new technology would be considered instantaneously value enhancing and thus financially feasible. However, future cash flows are highly uncertain, which brings into question financial feasibility in a risky environment. To address the riskiness of future cash flows, I model three risk factors: the cost of raw materials, the potential growth in battery sales, as well as the potential mark-up (profit margin) of the SSE enterprise. Using Monte Carlo simulation (MCS) I model the incremental cash flows considering these risk factors and derive probabilistic assessments of NPV. My analysis suggests that despite the uncertainty caused by the volatility of raw metal prices, assumptions on price mark-up, and uncertain market demand for Li-ion batteries, there is a high probability of an investment in SSE batteries being financially feasible. Future research should consider the value of real options (optionality embedded in tangible investments) as traditional NPV analysis may underestimate the potential value of an investment in the presence of uncertain cash flows, especially if management has the ability to respond to the uncertainty.

ContributorsFonseca, Nathan (Author) / Manfredo, Mark (Thesis director) / Kannan, Arunachala Mada (Committee member) / Barrett, The Honors College (Contributor) / Engineering Programs (Contributor)
Created2022-05
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Description
Vitamin D is a nutrient that is obtained through the diet and vitamin D supplementation and created from exposure to Ultraviolet B (UVB) radiation. While there are many factors that determine how much serum 25-hydroxyvitamin D (25(OH)D) concentration is in the body, little is known about how genetic variation in

Vitamin D is a nutrient that is obtained through the diet and vitamin D supplementation and created from exposure to Ultraviolet B (UVB) radiation. While there are many factors that determine how much serum 25-hydroxyvitamin D (25(OH)D) concentration is in the body, little is known about how genetic variation in vitamin D-related genes influences serum 25(OH)D concentrations resulting from daily vitamin D intake and exposure to direct sunlight. Previous studies show that common genetic variants rs10741657 (CYP2R1), rs4588 (GC), rs228678 (GC), and rs4516035 (VDR) act as moderators and alter the effect of outdoor time and vitamin D intake on serum 25(OH)D concentrations. The objective of this study is to analyze the associations between serum 25(OH)D concentrations resulting from outdoor time and vitamin D intake, and genetic risk scores (GRS) established from previous studies involving single nucleotide polymorphisms (SNP) located on or near genes involving vitamin D synthesis, transport, activation, and degradation in 102 Hispanic and Non-Hispanic adults in the San Diego County, California. This study is a secondary analysis of data from the Community of Mine study. Global Positioning System (GPS) data collected by the Qstarz GPS device worn by each participant was used to measure outdoor time, a proxy measurement for sun exposure time. Vitamin D intake was assessed using two 24-hour dietary recalls. Blood samples were measured for serum 25(OH)D concentrations. DNA was provided to assess each participant for the various genetic variants. Adjusted analyses of the GRS and serum 25(OH)D concentrations showed that individuals with high GRS (3-4) had lower serum 25(OH)D concentrations than individuals with low GRS (0-2) for both Nissen GRS and Rivera-Paredez GRS.
ContributorsAnderson, Heather Ray (Author) / Sears, Dorothy (Thesis advisor) / Alexon, Christy (Committee member) / Dinu, Valentin (Committee member) / Jankowska, Marta (Committee member) / Arizona State University (Publisher)
Created2022
Description
Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their

Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their functional role and impact remains to be clarified, circRNAs have been found to regulate micro-RNAs (miRNAs) as well as parental gene transcription and may thus have key roles in transcriptional regulation. Although circRNAs have continued to gain attention, our understanding of their expression in a cell-, tissue- , and brain region-specific context remains limited. Further, computational algorithms produce varied results in terms of what circRNAs are detected. This thesis aims to advance current knowledge of circRNA expression in a region specific context focusing on the human brain, as well as address computational challenges.

The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
ContributorsSekar, Shobana (Author) / Liang, Winnie S (Thesis advisor) / Dinu, Valentin (Thesis advisor) / Craig, David (Committee member) / Liu, Li (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Clinical Decision Support (CDS) is primarily associated with alerts, reminders, order entry, rule-based invocation, diagnostic aids, and on-demand information retrieval. While valuable, these foci have been in production use for decades, and do not provide a broader, interoperable means of plugging structured clinical knowledge into live electronic health record (EHR)

Clinical Decision Support (CDS) is primarily associated with alerts, reminders, order entry, rule-based invocation, diagnostic aids, and on-demand information retrieval. While valuable, these foci have been in production use for decades, and do not provide a broader, interoperable means of plugging structured clinical knowledge into live electronic health record (EHR) ecosystems for purposes of orchestrating the user experiences of patients and clinicians. To date, the gap between knowledge representation and user-facing EHR integration has been considered an “implementation concern” requiring unscalable manual human efforts and governance coordination. Drafting a questionnaire engineered to meet the specifications of the HL7 CDS Knowledge Artifact specification, for example, carries no reasonable expectation that it may be imported and deployed into a live system without significant burdens. Dramatic reduction of the time and effort gap in the research and application cycle could be revolutionary. Doing so, however, requires both a floor-to-ceiling precoordination of functional boundaries in the knowledge management lifecycle, as well as formalization of the human processes by which this occurs.

This research introduces ARTAKA: Architecture for Real-Time Application of Knowledge Artifacts, as a concrete floor-to-ceiling technological blueprint for both provider heath IT (HIT) and vendor organizations to incrementally introduce value into existing systems dynamically. This is made possible by service-ization of curated knowledge artifacts, then injected into a highly scalable backend infrastructure by automated orchestration through public marketplaces. Supplementary examples of client app integration are also provided. Compilation of knowledge into platform-specific form has been left flexible, in so far as implementations comply with ARTAKA’s Context Event Service (CES) communication and Health Services Platform (HSP) Marketplace service packaging standards.

Towards the goal of interoperable human processes, ARTAKA’s treatment of knowledge artifacts as a specialized form of software allows knowledge engineers to operate as a type of software engineering practice. Thus, nearly a century of software development processes, tools, policies, and lessons offer immediate benefit: in some cases, with remarkable parity. Analyses of experimentation is provided with guidelines in how choice aspects of software development life cycles (SDLCs) apply to knowledge artifact development in an ARTAKA environment.

Portions of this culminating document have been further initiated with Standards Developing Organizations (SDOs) intended to ultimately produce normative standards, as have active relationships with other bodies.
ContributorsLee, Preston Victor (Author) / Dinu, Valentin (Thesis advisor) / Sottara, Davide (Committee member) / Greenes, Robert (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Study of canine cancer’s molecular underpinnings holds great potential for informing veterinary and human oncology. Sporadic canine cancers are highly abundant (~4 million diagnoses/year in the United States) and the dog’s unique genomic architecture due to selective inbreeding, alongside the high similarity between dog and human genomes both confer power

Study of canine cancer’s molecular underpinnings holds great potential for informing veterinary and human oncology. Sporadic canine cancers are highly abundant (~4 million diagnoses/year in the United States) and the dog’s unique genomic architecture due to selective inbreeding, alongside the high similarity between dog and human genomes both confer power for improving understanding of cancer genes. However, characterization of canine cancer genome landscapes has been limited. It is hindered by lack of canine-specific tools and resources. To enable robust and reproducible comparative genomic analysis of canine cancers, I have developed a workflow for somatic and germline variant calling in canine cancer genomic data. I have first adapted a human cancer genomics pipeline to create a semi-automated canine pipeline used to map genomic landscapes of canine melanoma, lung adenocarcinoma, osteosarcoma and lymphoma. This pipeline also forms the backbone of my novel comparative genomics workflow.

Practical impediments to comparative genomic analysis of dog and human include challenges identifying similarities in mutation type and function across species. For example, canine genes could have evolved different functions and their human orthologs may perform different functions. Hence, I undertook a systematic statistical evaluation of dog and human cancer genes and assessed functional similarities and differences between orthologs to improve understanding of the roles of these genes in cancer across species. I tested this pipeline canine and human Diffuse Large B-Cell Lymphoma (DLBCL), given that canine DLBCL is the most comprehensively genomically characterized canine cancer. Logistic regression with genes bearing somatic coding mutations in each cancer was used to determine if conservation metrics (sequence identity, network placement, etc.) could explain co-mutation of genes in both species. Using this model, I identified 25 co-mutated and evolutionarily similar genes that may be compelling cross-species cancer genes. For example, PCLO was identified as a co-mutated conserved gene with PCLO having been previously identified as recurrently mutated in human DLBCL, but with an unclear role in oncogenesis. Further investigation of these genes might shed new light on the biology of lymphoma in dogs and human and this approach may more broadly serve to prioritize new genes for comparative cancer biology studies.
ContributorsSivaprakasam, Karthigayini (Author) / Dinu, Valentin (Thesis advisor) / Trent, Jeffrey (Thesis advisor) / Hendricks, William (Committee member) / Runger, George C. (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Breast cancer is the most common cancer and currently the second leading cause of death among women in the United States. Patients’ five-year relative survival rate decreases from 99% to 25% when breast cancer is diagnosed late. Immune checkpoint blockage has shown to be a promising therapy to improve patients’

Breast cancer is the most common cancer and currently the second leading cause of death among women in the United States. Patients’ five-year relative survival rate decreases from 99% to 25% when breast cancer is diagnosed late. Immune checkpoint blockage has shown to be a promising therapy to improve patients’ outcome in many other cancers. However, due to the lack of early diagnosis, the treatment is normally given in the later stages. An early diagnosis system for breast cancer could potentially revolutionize current treatment strategies, improve patients’ outcomes and even eradicate the disease. The current breast cancer diagnostic methods cannot meet this demand. A simple, effective, noninvasive and inexpensive early diagnostic technology is needed. Immunosignature technology leverages the power of the immune system to find cancer early. Antibodies targeting tumor antigens in the blood are probed on a high-throughput random peptide array and generate a specific binding pattern called the immunosignature.

In this dissertation, I propose a scenario for using immunosignature technology to detect breast cancer early and to implement an early treatment strategy by using the PD-L1 immune checkpoint inhibitor. I develop a methodology to describe the early diagnosis and treatment of breast cancer in a FVB/N neuN breast cancer mouse model. By comparing FVB/N neuN transgenic mice and age-matched wild type controls, I have found and validated specific immunosignatures at multiple time points before tumors are palpable. Immunosignatures change along with tumor development. Using a late-stage immunosignature to predict early samples, or vice versa, cannot achieve high prediction performance. By using the immunosignature of early breast cancer, I show that at the time of diagnosis, early treatment with the checkpoint blockade, anti-PD-L1, inhibits tumor growth in FVB/N neuN transgenic mouse model. The mRNA analysis of the PD-L1 level in mice mammary glands suggests that it is more effective to have treatment early.

Novel discoveries are changing understanding of breast cancer and improving strategies in clinical treatment. Researchers and healthcare professionals are actively working in the early diagnosis and early treatment fields. This dissertation provides a step along the road for better diagnosis and treatment of breast cancer.
ContributorsDuan, Hu (Author) / Johnston, Stephen Albert (Thesis advisor) / Hartwell, Leland Harrison (Committee member) / Dinu, Valentin (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
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Description
No two cancers are alike. Cancer is a dynamic and heterogeneous disease, such heterogeneity arise among patients with the same cancer type, among cancer cells within the same individual’s tumor and even among cells within the same sub-clone over time. The recent application of next-generation sequencing and precision medicine techniques

No two cancers are alike. Cancer is a dynamic and heterogeneous disease, such heterogeneity arise among patients with the same cancer type, among cancer cells within the same individual’s tumor and even among cells within the same sub-clone over time. The recent application of next-generation sequencing and precision medicine techniques is the driving force to uncover the complexity of cancer and the best clinical practice. The core concept of precision medicine is to move away from crowd-based, best-for-most treatment and take individual variability into account when optimizing the prevention and treatment strategies. Next-generation sequencing is the method to sift through the entire 3 billion letters of each patient’s DNA genetic code in a massively parallel fashion.

The deluge of next-generation sequencing data nowadays has shifted the bottleneck of cancer research from multiple “-omics” data collection to integrative analysis and data interpretation. In this dissertation, I attempt to address two distinct, but dependent, challenges. The first is to design specific computational algorithms and tools that can process and extract useful information from the raw data in an efficient, robust, and reproducible manner. The second challenge is to develop high-level computational methods and data frameworks for integrating and interpreting these data. Specifically, Chapter 2 presents a tool called Snipea (SNv Integration, Prioritization, Ensemble, and Annotation) to further identify, prioritize and annotate somatic SNVs (Single Nucleotide Variant) called from multiple variant callers. Chapter 3 describes a novel alignment-based algorithm to accurately and losslessly classify sequencing reads from xenograft models. Chapter 4 describes a direct and biologically motivated framework and associated methods for identification of putative aberrations causing survival difference in GBM patients by integrating whole-genome sequencing, exome sequencing, RNA-Sequencing, methylation array and clinical data. Lastly, chapter 5 explores longitudinal and intratumor heterogeneity studies to reveal the temporal and spatial context of tumor evolution. The long-term goal is to help patients with cancer, particularly those who are in front of us today. Genome-based analysis of the patient tumor can identify genomic alterations unique to each patient’s tumor that are candidate therapeutic targets to decrease therapy resistance and improve clinical outcome.
ContributorsPeng, Sen (Author) / Dinu, Valentin (Thesis advisor) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Increasing demand for reducing the stress on fossil fuels has motivated automotive industries to shift towards sustainable modes of transport through electric and hybrid electric vehicles. Most fuel efficient cars of year 2016 are hybrid vehicles as reported by environmental protection agency. Hybrid vehicles operate with internal combustion engine and

Increasing demand for reducing the stress on fossil fuels has motivated automotive industries to shift towards sustainable modes of transport through electric and hybrid electric vehicles. Most fuel efficient cars of year 2016 are hybrid vehicles as reported by environmental protection agency. Hybrid vehicles operate with internal combustion engine and electric motors powered by batteries, and can significantly improve fuel economy due to downsizing of the engine. Whereas, Plug-in hybrids (PHEVs) have an additional feature compared to hybrid vehicles i.e. recharging batteries through external power outlets. Among hybrid powertrains, lithium-ion batteries have emerged as a major electrochemical storage source for propulsion of vehicles.

In PHEVs, batteries operate under charge sustaining and charge depleting mode based on torque requirement and state of charge. In the current article, 26650 lithium-ion cells were cycled extensively at 25 and 50 oC under charge sustaining mode to monitor capacity and cell impedance values followed by analyzing the Lithium iron phosphate (LiFePO4) cathode material by X-ray diffraction analysis (XRD). High frequency resistance measured by electrochemical impedance spectroscopy was found to increase significantly under high temperature cycling, leading to power fading. No phase change in LiFePO4 cathode material is observed after 330 cycles at elevated temperature under charge sustaining mode from the XRD analysis. However, there was significant change in crystallite size of the cathode active material after charge/discharge cycling with charge sustaining mode. Additionally, 18650 lithium-ion cells were tested under charge depleting mode to monitor capacity values.
ContributorsBadami, Pavan Pramod (Author) / Kannan, Arunachala Mada (Thesis advisor) / Huang, Huei Ping (Thesis advisor) / Ren, Yi (Committee member) / Arizona State University (Publisher)
Created2016