ASU Scholarship Showcase
This growing collection consists of scholarly works authored by ASU-affiliated faculty, staff, and community members, and it contains many open access articles. ASU-affiliated authors are encouraged to Share Your Work in KEEP.
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- Language: English
- Creators: Anderies, John
- Creators: Preul, Mark C.
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.
Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies.
Methods: Review of the literature.
Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.
Conclusion: We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.
Background: The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.
Methods: To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.
Results: Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.
Conclusions: The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.
Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4∶1 (fat∶ carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.
Methods: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.
Results: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.
Conclusions: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.
Ecological models are a fundamental tool that archaeologists use to clarify our thinking about the processes that generate the archaeological record. Typically, arguments reasoned from a single model are bolstered by observing the consistency of ethnographic data with the argument. This validation of a model establishes that an argument is reasonable. In this paper, we attempt to move beyond validation by comparing the consistency of two arguments reasoned from different models that might explain corporate territorial ownership in a large ethnographic data set. Our results suggest that social dilemmas are an under appreciated mechanism that can drive the evolution of corporate territorial ownership. When social dilemmas emerge, the costs associated with provisioning the public goods of information on resources or, perhaps, common defence create situations in which human foragers gain more by cooperating to recognize corporate ownership rules than they lose. Our results also indicate that societies who share a common cultural history are more likely to recognize corporate ownership, and there is a spatial dynamic in which societies who live near each other are more likely to recognize corporate ownership as the number of near-by groups who recognize ownership increases. Our results have important implications for investigating the coevolution of territorial ownership and the adoption of food production in the archaeological record.
Background: Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia.
Methods: Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet.
Results: Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4.
Conclusions: Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.
The insights in Governing the Commons have provided foundational ideas for commons research in the past 23 years. However, the cases that Elinor Ostrom analyzed have been exposed to new social, economic, and ecological disturbances. What has happened to these cases since the 1980s? We reevaluated one of Ostrom’s case studies, the lobster and groundfishery of Port Lameron, Southwest Nova Scotia (SWNS). Ostrom suggested that the self-governance of this fishery was fragile because the government did not recognize the rights of resource users to organize their own rules. In the Maine lobster fishery, however, the government formalized customary rules and decentralized power to fishing ports. We applied the concepts of feedback, governance mismatches, and the robustness of social-ecological systems to understand the pathway of institutional change in Port Lameron. We revisited the case of Port Lameron using marine harvesters’ accounts collected from participant observation, informal interviews and surveys, and literature on fisheries policy and ecology in SWNS and Maine. We found that the government’s failure to recognize the customary rights of harvesters to organize has weakened feedback between the operational level, where resource users interact with the resource, and the collective-choice level, where agents develop rules to influence the behavior of resource users. This has precipitated governance mismatches, which have led harvesters to believe that the decision-making process is detrimental to their livelihoods. Thus, harvesters rarely participate in decision making and resist regulatory change. In Maine, harvesters can influence decisions through participation, but there is a trade-off. With higher influence in decisions, captains have co-opted the decision-making process. Nevertheless, we suggest that the fisheries of SWNS are more vulnerable to social-ecological change because of weaker feedbacks than in Maine. Finally, we have discussed the potential benefits of polycentricity to both fisheries.