ASU Scholarship Showcase

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm³ to 62 mm³, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

In this synthesis, we hope to accomplish two things: 1) reflect on how the analysis of the new archaeological cases presented in this special feature adds to previous case studies by revisiting a set of propositions reported in a 2006 special feature, and 2) reflect on four main ideas that are more specific to the archaeological cases: i) societal choices are influenced by robustness–vulnerability trade-offs, ii) there is interplay between robustness–vulnerability trade-offs and robustness–performance trade-offs, iii) societies often get locked in to particular strategies, and iv) multiple positive feedbacks escalate the perceived cost of societal change. We then discuss whether these lock-in traps can be prevented or whether the risks associated with them can be mitigated. We conclude by highlighting how these long-term historical studies can help us to understand current society, societal practices, and the nexus between ecology and society.

What relationships can be understood between resilience and vulnerability in social-ecological systems? In particular, what vulnerabilities are exacerbated or ameliorated by different sets of social practices associated with water management? These questions have been examined primarily through the study of contemporary or recent historic cases. Archaeology extends scientific observation beyond all social memory and can thus illuminate interactions occurring over centuries or millennia. We examined trade-offs of resilience and vulnerability in the changing social, technological, and environmental contexts of three long-term, pre-Hispanic sequences in the U.S. Southwest: the Mimbres area in southwestern New Mexico (AD 650–1450), the Zuni area in northern New Mexico (AD 850–1540), and the Hohokam area in central Arizona (AD 700–1450). In all three arid landscapes, people relied on agricultural systems that depended on physical and social infrastructure that diverted adequate water to agricultural soils. However, investments in infrastructure varied across the cases, as did local environmental conditions. Zuni farming employed a variety of small-scale water control strategies, including centuries of reliance on small runoff agricultural systems; Mimbres fields were primarily watered by small-scale canals feeding floodplain fields; and the Hohokam area had the largest canal system in pre-Hispanic North America. The cases also vary in their historical trajectories: at Zuni, population and resource use remained comparatively stable over centuries, extending into the historic period; in the Mimbres and Hohokam areas, there were major demographic and environmental transformations. Comparisons across these cases thus allow an understanding of factors that promote vulnerability and influence resilience in specific contexts.

Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.

Results:
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.

Conclusions:
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.

On-going efforts to understand the dynamics of coupled social-ecological (or more broadly, coupled infrastructure) systems and common pool resources have led to the generation of numerous datasets based on a large number of case studies. This data has facilitated the identification of important factors and fundamental principles which increase our understanding of such complex systems. However, the data at our disposal are often not easily comparable, have limited scope and scale, and are based on disparate underlying frameworks inhibiting synthesis, meta-analysis, and the validation of findings. Research efforts are further hampered when case inclusion criteria, variable definitions, coding schema, and inter-coder reliability testing are not made explicit in the presentation of research and shared among the research community. This paper first outlines challenges experienced by researchers engaged in a large-scale coding project; then highlights valuable lessons learned; and finally discusses opportunities for further research on comparative case study analysis focusing on social-ecological systems and common pool resources. Includes supplemental materials and appendices published in the International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016.

Governing common pool resources (CPR) in the face of disturbances such as globalization and climate change is challenging. The outcome of any CPR governance regime is the influenced by local combinations of social, institutional, and biophysical factors, as well as cross-scale interdependencies. In this study, we take a step towards understanding multiple-causation of CPR outcomes by analyzing 1) the co-occurrence of Design Principles (DP) by activity (irrigation, fishery and forestry), and 2) the combination(s) of DPs leading to social and ecological success. We analyzed 69 cases pertaining to three different activities: irrigation, fishery, and forestry. We find that the importance of the design principles is dependent upon the natural and hard human made infrastructure (i.e. canals, equipment, vessels etc.). For example, clearly defined social boundaries are important when the natural infrastructure is highly mobile (i.e. tuna fish), while monitoring is more important when the natural infrastructure is more static (i.e. forests or water contained within an irrigation system). However, we also find that congruence between local conditions and rules and proportionality between investment and extraction are key for CPR success independent from the natural and human hard made infrastructure. We further provide new visualization techniques for co-occurrence patterns and add to qualitative comparative analysis by introducing a reliability metric to deal with a large meta-analysis dataset on secondary data where information is missing or uncertain.

Includes supplemental materials and appendices publications in International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016

Precise spatial positioning and isolation of mammalian cells is a critical component of many single cell experimental methods and biological engineering applications. Although a variety of cell patterning methods have been demonstrated, many of these methods subject cells to high stress environments, discriminate against certain phenotypes, or are a challenge to implement. Here, we demonstrate a rapid, simple, indiscriminate, and minimally perturbing cell patterning method using a laser fabricated polymer stencil. The stencil fabrication process requires no stencil-substrate alignment, and is readily adaptable to various substrate geometries and experiments.

Quantitative three-dimensional (3D) computed tomography (CT) imaging of living single cells enables orientation-independent morphometric analysis of the intricacies of cellular physiology. Since its invention, x-ray CT has become indispensable in the clinic for diagnostic and prognostic purposes due to its quantitative absorption-based imaging in true 3D that allows objects of interest to be viewed and measured from any orientation. However, x-ray CT has not been useful at the level of single cells because there is insufficient contrast to form an image. Recently, optical CT has been developed successfully for fixed cells, but this technology called Cell-CT is incompatible with live-cell imaging due to the use of stains, such as hematoxylin, that are not compatible with cell viability. We present a novel development of optical CT for quantitative, multispectral functional 4D (three spatial + one spectral dimension) imaging of living single cells. The method applied to immune system cells offers truly isotropic 3D spatial resolution and enables time-resolved imaging studies of cells suspended in aqueous medium. Using live-cell optical CT, we found a heterogeneous response to mitochondrial fission inhibition in mouse macrophages and differential basal remodeling of small (0.1 to 1 fl) and large (1 to 20 fl) nuclear and mitochondrial structures on a 20- to 30-s time scale in human myelogenous leukemia cells. Because of its robust 3D measurement capabilities, live-cell optical CT represents a powerful new tool in the biomedical research field.

With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH₂) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields.