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- Creators: Koch, Carolyn
- Creators: Ira A. Fulton Schools of Engineering
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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
Recent studies indicate the presence of nano-scale titanium dioxide (TiO[subscript 2]) as an additive in human foodstuffs, but a practical protocol to isolate and separate nano-fractions from soluble foodstuffs as a source of material remains elusive. As such, we developed a method for separating the nano and submicron fractions found in commercial-grade TiO[subscript 2] (E171) and E171 extracted from soluble foodstuffs and pharmaceutical products (e.g., chewing gum, pain reliever, and allergy medicine). Primary particle analysis of commercial-grade E171 indicated that 54% of particles were nano-sized (i.e., < 100 nm). Isolation and primary particle analysis of five consumer goods intended to be ingested revealed differences in the percent of nano-sized particles from 32%‒58%. Separation and enrichment of nano- and submicron-sized particles from commercial-grade E171 and E171 isolated from foodstuffs and pharmaceuticals was accomplished using rate-zonal centrifugation. Commercial-grade E171 was separated into nano- and submicron-enriched fractions consisting of a nano:submicron fraction of approximately 0.45:1 and 3.2:1, respectively. E171 extracted from gum had nano:submicron fractions of 1.4:1 and 0.19:1 for nano- and submicron-enriched, respectively. We show a difference in particle adhesion to the cell surface, which was found to be dependent on particle size and epithelial orientation. Finally, we provide evidence that E171 particles are not immediately cytotoxic to the Caco-2 human intestinal epithelium model. These data suggest that this separation method is appropriate for studies interested in isolating the nano-sized particle fraction taken directly from consumer products, in order to study separately the effects of nano and submicron particles.
ContributorsFaust, James (Author) / Doudrick, Kyle (Author) / Yang, Yu (Author) / Capco, David (Author) / Westerhoff, Paul (Author) / College of Liberal Arts and Sciences (Contributor) / Molecular and Cellular Biology (Contributor) / School of Life Sciences (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / School of Sustainable Engineering and the Built Environment (Contributor)
Created2016-10-31
Description
Lonsdaleite, also called hexagonal diamond, has been widely used as a marker of asteroidal impacts. It is thought to play a central role during the graphite-to-diamond transformation, and calculations suggest that it possesses mechanical properties superior to diamond. However, despite extensive efforts, lonsdaleite has never been produced or described as a separate, pure material. Here we show that defects in cubic diamond provide an explanation for the characteristic d-spacings and reflections reported for lonsdaleite. Ultrahigh-resolution electron microscope images demonstrate that samples displaying features attributed to lonsdaleite consist of cubic diamond dominated by extensive {113} twins and {111} stacking faults. These defects give rise to nanometre-scale structural complexity. Our findings question the existence of lonsdaleite and point to the need for re-evaluating the interpretations of many lonsdaleite-related fundamental and applied studies.
ContributorsNemeth, Peter (Author) / Garvie, Laurence (Author) / Aoki, Toshihiro (Author) / Dubrovinskaia, Natalia (Author) / Dubrovinsky, Leonid (Author) / Buseck, Peter (Author) / Department of Chemistry and Biochemistry (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Earth and Space Exploration (Contributor) / Center for Meteorite Studies (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / LeRoy Eyring Center for Solid State Science (Contributor) / School of Molecular Sciences (Contributor)
Created2014-11-01
Description
Because metallic aircraft components are subject to a variety of in-service loading conditions, predicting their fatigue life has become a critical challenge. To address the failure mode mitigation of aircraft components and at the same time reduce the life-cycle costs of aerospace systems, a reliable prognostics framework is essential. In this paper, a hybrid prognosis model that accurately predicts the crack growth regime and the residual-useful-life estimate of aluminum components is developed. The methodology integrates physics-based modeling with a data-driven approach. Different types of loading conditions such as constant amplitude, random, and overload are investigated. The developed methodology is validated on an Al 2024-T351 lug joint under fatigue loading conditions. The results indicate that fusing the measured data and physics-based models improves the accuracy of prediction compared to a purely data-driven or physics-based approach.
ContributorsNeerukatti, Rajesh Kumar (Author) / Liu, Kuang C. (Author) / Kovvali, Narayan (Author) / Chattopadhyay, Aditi (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School for the Engineering of Matter, Transport and Energy (Contributor)
Created2014-04-01
Description
High phase order systems have been proposed at the early inception of power transmission engineering, but few direct applications have been made. High phase order transmission should be considered as an alternative in the case of high power density applications. In this article, an analysis of transposition of high phase order overhead transmission lines is presented and voltage unbalance in high phase order systems is considered. Definitions are presented for “fully transposed” and “roll transposed” along with advantages and disadvantages of each. A generalized voltage unbalance factor is introduced and utilized to determine the benefits of transposition. The generalized voltage unbalance factor is compared with three other possible unbalance factors to determine if the generalized voltage unbalance factor is an appropriate indication of unbalance. Exemplary results are presented for 6-phase and 12-phase designs. Conclusions show that the generalized voltage unbalance factor is a good indication of transmission line voltage unbalance and certain configurations may not need full rotation transposition to minimize the unbalance factor. The transposition analysis and voltage unbalance are considerations in the assessment of high phase order as a high power transmission alternative.
ContributorsPierre, Brian (Author) / Heydt, Gerald (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School for the Engineering of Matter, Transport and Energy (Contributor)
Created2014-11-18
Description
The increase of transmission line thermal ratings by reconductoring with high temperature low sag conductors is a comparatively new technology introduced for transmission expansion. A special design permits high temperature low sag conductors to operate at higher temperatures, therefore allowing passage of higher current and, thus, increasing the thermal rating of the transmission line. The comparatively high cost of high temperature low sag conductors may be an obstacle to its large-scale implementation. This article evaluates the expenditures for transmission line reconductoring using high temperature low sag, the consequent benefits obtained from the potential decrease in operating cost for thermally limited power transmission systems. Estimates of the “payback period” are used to evaluate the cost effectiveness of reconductoring with high temperature low sag. The evaluation is performed using a 225 bus equivalent of the 2012 summer peak Arizona portion of the Western Electricity Coordinating Council. The method is offered for transmission expansion analysis in which an economic benefit is calculated to assist in the transmission expansion decision.
ContributorsTokombayev, Askhat (Author) / Heydt, Gerald (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School of Electrical, Computer and Energy Engineering (Contributor)
Created2015-02-07
Description
Eigenvalues of the 3D critical point equation (∇u)ν = λν are normally computed numerically. In the letter, we present analytic solutions for 3D swirling strength in both compressible and incompressible flows. The solutions expose functional dependencies that cannot be seen in numerical solutions. To illustrate, we study the difference between using fluctuating and total velocity gradient tensors for vortex identification. Results show that mean shear influences vortex detection and that distortion can occur, depending on the strength of mean shear relative to the vorticity at the vortex center.
ContributorsChen, Huai (Author) / Adrian, Ronald (Author) / Zhong, Qiang (Author) / Wang, Xingkui (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School for the Engineering of Matter, Transport and Energy (Contributor)
Created2014-08-01
Description
The flexural behavior of epoxies was investigated by performing mechanical tests and applying statistical Weibull theory and analytical methods to the results. The effects of loading systems and environmental conditions were also considered. Three kinds of epoxies were studied: Epon E863, PRI 2002, and PR520. In total, 53 three-point-bending (3PB) Epon E863 samples and 26 3PB PR520 were tested immediately after curing, together with 26 four-point-bending (4PB) PRI2002 samples stored at 60°C and 90% Rh for 48 weeks. The Weibull parameters were estimated using both linear regression and the moments method. The statistical character of the Weibull model leads to uncertainty in the evaluated parameters, even for a large number of experiments. This study analyzed the ratio of flexural strength to tensile strength in bulk epoxy resin polymers. An analytical method previously developed by the authors to study the relationship between uniaxial tension/compression stress-strain curves and flexural load-deflection response was used to obtain the ratio. The results show that the Weibull model overpredicted the aforementioned ratio in different load arrangements.
ContributorsYekani Fard, Masoud (Author) / Raji, B. (Author) / Chattopadhyay, Aditi (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School for the Engineering of Matter, Transport and Energy (Contributor)
Created2014-12-01
Description
Identification of early damage in polymer composites is of great importance. We have incorporated cyclobutane-containing cross-linked polymers into an epoxy matrix, studied the effect on thermal and mechanical properties, and, more importantly, demonstrated early damage detection through mechanically induced fluorescence generation. Two cinnamate derivatives, 1,1,1-tris(cinnamoyloxymethyl) ethane (TCE) and poly(vinyl cinnamate) (PVCi), were photoirradiated to produce cyclobutane-containing polymer. The effects on the thermal and mechanical properties with the addition of cyclobutane-containing polymer into epoxy matrix were investigated. The emergence of cracks was detected by fluorescence at a strain level just beyond the yield point of the polymer blends, and the fluorescence intensified with accumulation of strain. Overall, the results show that damage can be detected through fluorescence generation along crack propagation.
ContributorsZou, Jin (Author) / Liu, Yingtao (Author) / Shan, Bohan (Author) / Chattopadhyay, Aditi (Author) / Dai, Lenore (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School for the Engineering of Matter, Transport and Energy (Contributor)
Created2014-09-01
Description
The impact of increasing penetration of converter control-based generators (CCBGs) in a large-scale power system is assessed through a model based small signal stability analysis. Three test bed cases for the years 2010, 2020, and 2022 of the Western Electricity Coordinating Council (WECC) in the United States are used for the analysis. Increasing penetration of wind-based Type 3 and wind-based Type 4 and PV Solar CCBGs is used in the tests. The participation and interaction of CCBGs and synchronous generators in traditional electromechanical interarea modes is analyzed. Two new types of modes dominated by CCBGs are identified. The characteristics of these new modes are described and compared to electromechanical modes in the frequency domain. An examination of the mechanism of the interaction between the CCBG control states and the synchronous generator control states is presented and validated through dynamic simulations. Actual system and forecast load data are used throughout.
ContributorsQuintero, Jaime (Author) / Vittal, Vijay (Author) / Heydt, Gerald (Author) / Zhang, Hui (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School of Electrical, Computer and Energy Engineering (Contributor)
Created2014-09-01