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Description
Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of single cells. Yet to date, no live-cell compatible version of the technology exists. In this thesis, a microfluidic chip with the ability to rotate live single cells in hydrodynamic microvortices about an axis parallel to the optical focal plane has been demonstrated. The chip utilizes a novel 3D microchamber design arranged beneath a main channel creating flow detachment into the chamber, producing recirculating flow conditions. Single cells are flowed through the main channel, held in the center of the microvortex by an optical trap, and rotated by the forces induced by the recirculating fluid flow. Computational fluid dynamics (CFD) was employed to optimize the geometry of the microchamber. Two methods for the fabrication of the 3D microchamber were devised: anisotropic etching of silicon and backside diffuser photolithography (BDPL). First, the optimization of the silicon etching conditions was demonstrated through design of experiment (DOE). In addition, a non-conventional method of soft-lithography was demonstrated which incorporates the use of two positive molds, one of the main channel and the other of the microchambers, compressed together during replication to produce a single ultra-thin (<200 µm) negative used for device assembly. Second, methods for using thick negative photoresists such as SU-8 with BDPL have been developed which include a new simple and effective method for promoting the adhesion of SU-8 to glass. An assembly method that bonds two individual ultra-thin (<100 µm) replications of the channel and the microfeatures has also been demonstrated. Finally, a pressure driven pumping system with nanoliter per minute flow rate regulation, sub-second response times, and < 3% flow variability has been designed and characterized. The fabrication and assembly of this device is inexpensive and utilizes simple variants of conventional microfluidic fabrication techniques, making it easily accessible to the single cell analysis community.
ContributorsMyers, Jakrey R (Author) / Meldrum, Deirdre (Thesis advisor) / Johnson, Roger (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread. Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population. The behavioral factors that underpin contact rates are not generally addressed. There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact. Referred to as “economic epidemiology” or “epidemiological economics,” the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics. We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management.
ContributorsPerrings, Charles (Author) / Castillo-Chavez, Carlos (Author) / Chowell-Puente, Gerardo (Author) / Daszak, Peter (Author) / Fenichel, Eli P. (Author) / Finnoff, David (Author) / Horan, Richard D. (Author) / Kilpatrick, A. Marm (Author) / Kinzig, Ann (Author) / Kuminoff, Nicolai (Author) / Levin, Simon (Author) / Morin, Benjamin (Author) / Smith, Katherine F. (Author) / Springborn, Michael (Author) / Simon M. Levin Mathematical, Computational and Modeling Sciences Center (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / W.P. Carey School of Business (Contributor) / Economics (Contributor) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2015-12-01
Description
Background
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.
ContributorsNandakumar, Vivek (Author) / Kelbauskas, Laimonas (Author) / Hernandez, Kathryn (Author) / Lintecum, Kelly (Author) / Senechal, Patti (Author) / Bussey, Kimberly (Author) / Davies, Paul (Author) / Johnson, Roger (Author) / Meldrum, Deirdre (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School of Electrical, Computer and Energy Engineering (Contributor) / Biodesign Institute (Contributor) / Center for Biosignatures Discovery Automation (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Department of Physics (Contributor)
Created2012-01-05
Description
While non-invasive breast cancer treatments may be considered less costly in the short-term, over the course of a lifetime, a more aggressive treatment can be overall less costly, especially with recurrence cases; however, these more aggressive treatments are not necessarily covered by insurance and are difficult to discuss in the short amount of time in physician consultations. This analysis studied data from 982 women diagnosed with breast cancer over a five-year period to evaluate monetary costs associated with treatment options and incorporated five in-depth interviews to understand experiences and non-monetary costs. Data showed the most expensive option was a unilateral mastectomy with radiation therapy and the least costly option was breast conserving surgery. Interviews determined each woman evaluated the monetary costs with each treatment but most heavily focused on personal values, biases and recommended opinions when deciding on a treatment. The use of prompt sheets before physician appointments and consultations, along with the addition of financial counselor meeting with each patient can improve patient satisfaction and alleviate stress by simplifying a woman's choice in deciding a treatment. In addition, increased insurance coverage to include every treatment chosen by women (rather than on a case-by-case basis), specifically contralateral prophylactic mastectomy and additional screening options, could decrease long term costs \u2014 both monetarily and in quality of life for patients.
ContributorsOsumi, Alana (Author) / LaRosa, Julia (Thesis director) / Sivanantham, Jai (Committee member) / Barrett, The Honors College (Contributor) / W.P. Carey School of Business (Contributor)
Created2018-12
Description
In 2016, in the United States alone, the cosmetics industry made an estimated 62.46 billion dollars in revenue (Revenue of the Cosmetic Industry in the U.S. 2002-2016 | Forecast). With a consistent increase in sales in the last several years, the industry has reached continued success even during times of hardship, such as the Great Recession of 2008. The use of Corporate Social Responsibility (CSR), external campaigns, and thoughtful packaging and ingredients resonates with targeted consumers. This has served as an effective strategy to maintain growth in the industry. Cosmetic companies promote their brand image using these sustainability tactics, but there seems to be a lack of transparency in this unregulated industry. The purpose of this thesis is to determine if the cosmetics industry is a good steward of the sustainability movement. Important terms and concepts relating to the industry will be discussed, then an analysis of sustainability focused cosmetic brands will be provided, which highlights the extent to which these brands engage in activities that promote sustainability. This is followed by an application of findings to a company that could benefit from using such practices. Overall, the analysis of the different brands proved to be shocking and disappointing. This is due to the sheer amount that scored very poorly based on the sustainability criteria developed. The cosmetics industry is too inconsistent and too unregulated to truly act as a good steward for sustainability. Though some companies in the industry succeed, these accomplishments are not consistent across all cosmetic companies. Hence, the cosmetics industry as a good steward for sustainability can only be as strong as its weakest link.
ContributorsMamus, Sydney Wasescha (Author) / Ostrom, Amy (Thesis director) / Kristofferson, Kirk (Committee member) / Department of Marketing (Contributor) / W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This report was commissioned to provide an analysis and evaluation of consumer perceptions and branding as it relates to the political and social climate in America. To be able to do this, the paper analyzes shifts in the external environment as well as researching case studies and online consumer perception surveys. Overall, this paper aims to examine the distributed survey and attempt to correlate and identify how branding, consumer perceptions, and social and political issues all can work and affect one another. Through the administration of this survey, we were able to formulate a conclusion that points towards the importance of brands actively adhering to changing consumer preferences, ideals, and expectations.
ContributorsClark, Sydney (Co-author) / Loera, Carolina (Co-author) / Montoya, Detra (Thesis director) / Samper, Adriana (Committee member) / W.P. Carey School of Business (Contributor) / Department of Marketing (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The use of generalized linear models in loss reserving is not new; many statistical models have been developed to fit the loss data gathered by various insurance companies. The most popular models belong to what Glen Barnett and Ben Zehnwirth in "Best Estimates for Reserves" call the "extended link ratio family (ELRF)," as they are developed from the chain ladder algorithm used by actuaries to estimate unpaid claims. Although these models are intuitive and easy to implement, they are nevertheless flawed because many of the assumptions behind the models do not hold true when fitted with real-world data. Even more problematically, the ELRF cannot account for environmental changes like inflation which are often observed in the status quo. Barnett and Zehnwirth conclude that a new set of models that contain parameters for not only accident year and development period trends but also payment year trends would be a more accurate predictor of loss development. This research applies the paper's ideas to data gathered by Company XYZ. The data was fitted with an adapted version of Barnett and Zehnwirth's new model in R, and a trend selection algorithm was developed to accompany the regression code. The final forecasts were compared to Company XYZ's booked reserves to evaluate the predictive power of the model.
ContributorsZhang, Zhihan Jennifer (Author) / Milovanovic, Jelena (Thesis director) / Tomita, Melissa (Committee member) / Zicarelli, John (Committee member) / W.P. Carey School of Business (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This research aims to look at the lower level collegiate athletics, Intramural sports and club sports, in comparison to Division 1 varsity athletics to see how their sport lives differ and why they are still competing when the reward does not seem as grand as the Varsity athletics. The findings show that the socially ingrained aspect of sports is the reason that most lower level athletes keep competing.
ContributorsHarvey, Abigail (Author) / Jonsson, Hjorleifur (Thesis director) / Jackson, Victoria (Committee member) / School of Human Evolution and Social Change (Contributor) / W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This report will provide an analysis of frontier market equity-based investment funds with respect to bivariate correlation analysis, global integration analysis, and US optimized portfolio statistics. My analysis has indicated strong diversification benefits of including frontier market equities in a US portfolio, given its low correlation to US equity concentrated portfolios especially portfolios that would consist of midcap and smallcap stocks. With the drawbacks of the bivariate correlation test, an additional global integration analysis has been included to reaffirm the value frontier markets offer in the form of integration. Integration is a second layer of the diversification analysis. I find that when analyzing frontier markets (FM) against developed markets (DM) there exhibits significantly less integration as compared to emerging markets against developed markets. This analysis goes one step further and quantifies integration of specific frontier market funds against the broader emerging and developed markets. This study finds that iShares MSCI frontier 100 ETF (Ticker: FM) exhibits the least integration amongst Guggenheim Frontier Markets ETF (Ticker: FRN), Templeton Frontier Markets A (Ticker: TFMAX), and Morgan Stanley Frontier Emg (Ticker: MFMIX). Lastly, this analysis covers the inadequacy with using Sharpe ratios and minimum volatility parameters to achieve portfolio optimization under a Monte-Carlo style 1000 portfolio simulation with frontier market funds in a broader US equity portfolio but finds better results when using a US equity and US bond combination portfolio. Overall, this analysis of frontier markets and frontier market funds has shown there still exists significant diversification benefits to US Investors when they engage in FM investments, specifically through diversified FM investment funds.
ContributorsHardy, Gunner Laine (Author) / Pruitt, Seth (Thesis director) / Brada, Josef (Committee member) / W.P. Carey School of Business (Contributor) / Economics Program in CLAS (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Research on California water markets has historically made two inaccurate assumptions regarding water rights: that water is a one-dimensional commodity, and that every water rights holder is in the market to sell. In reality, water is a bundled good that comprises varying attributes, and the decision to become a seller often has more to do with politics than price. This thesis analyzes the heterogeneous dimensions of a water right to explain the evolution of supply, demand, and price in California water markets. A dataset of 712 short-term surface water transfers in California from the period of 1990 through 2016 is analyzed to explain market trends and model the price of water. The data comes from a proprietary dataset of water transfers provided by WestWater Research, LLC (WestWater). Transfer data is distinguished based on variables such as buyer and seller experience, perennial crop plantings, seasonal timing of sale, buyer and seller region, water-year type, and end use. A variety of figures present summary statistics of the data. Ordinary Least Squares (OLS) regression is used to identify variables that are statistically significant in estimating the unit price of water in dollars per acre-foot ($/AF). The regression shows that State Water Bank (SWB) purchases, Environmental Water Account (EWA) purchases, environmental end use, North of Delta (NOD) seller location, the San Joaquin Valley Water-Year Index (San Joaquin Index), total perennial crop acreage, and purchases made by South Coast buyers were statistically significant at the 95% or 99% confidence interval. These variables were included in the final econometric model to estimate price.
ContributorsArnao, Audrey Louise (Author) / Hanemann, Michael (Thesis director) / Payne, Matthew (Committee member) / W.P. Carey School of Business (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05