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.
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.
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.
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.
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.
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.
Performance evaluation and characterization of lithium-ion cells under simulated PHEVs' drive cycles
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.