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.

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.

Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), contained more cells with decreased apoptosis, increased proliferation and enhanced levels of total RNA compared to static recellularization conditions. These results were observed with two relevant mouse cell types: bone marrow-derived mesenchymal stromal (stem) cells (MSCs) and alveolar type II cells (C10). In addition, MSCs cultured in decellularized lungs under static but not bioreactor conditions formed multilayered aggregates. Gene expression and immunohistochemical analyses suggested differentiation of MSCs into collagen I-producing fibroblast-like cells in the bioreactor, indicating enhanced potential for remodeling of the decellularized scaffold matrix. In conclusion, dynamic suspension culture is promising for enhancing repopulation of decellularized lungs, and could contribute to remodeling the extracellular matrix of the scaffolds with subsequent effects on differentiation and functionality of inoculated cells.

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established.

Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines.

A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD⁵⁰ of D23580 in female BALB/c mice was 4.7 x 10⁵ CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

Predicting the timing of a castrate resistant prostate cancer is critical to lowering medical costs and improving the quality of life of advanced prostate cancer patients. We formulate, compare and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). We accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). While these models are simplifications of a previously published model, they fit data with similar accuracy and improve forecasting results. Both models describe the progression of androgen resistance. Although Model 1 is simpler than the more realistic Model 2, it can fit clinical data to a greater precision. However, we found that Model 2 can forecast future PSA levels more accurately. These findings suggest that including more realistic mechanisms of androgen dynamics in a two population model may help androgen resistance timing prediction.

The Quadrangles Av-11 and Av-12 on Vesta are located at the northern rim of the giant Rheasilvia south polar impact basin. The primary geologic units in Av-11 and Av-12 include material from the Rheasilvia impact basin formation, smooth material and different types of impact crater structures (such as bimodal craters, dark and bright crater ray material and dark ejecta material). Av-11 and Av-12 exhibit almost the full range of mass wasting features observed on Vesta, such as slump blocks, spur-and-gully morphologies and landslides within craters. Processes of collapse, slope instability and seismically triggered events force material to slump down crater walls or scarps and produce landslides or rotational slump blocks. The spur-and-gully morphology that is known to form on Mars is also observed on Vesta; however, on Vesta this morphology formed under dry conditions.

A variety of geologic landforms and features are observed within quadrangle Av-13 Tuccia in the southern hemisphere of Vesta. The quadrangle covers parts of the highland Vestalia Terra as well as the floors of the large Rheasilvia and Veneneia impact basins, which results in a substantial elevation difference of more than 40 km between the northern and the southern portions of the quadrangle. Measurements of crater size–frequency distributions within and surrounding the Rheasilvia basin indicate that gravity-driven mass wasting in the interior of the basin has been important, and that the basin has a more ancient formation age than would be expected from the crater density on the basin floor alone. Subsequent to its formation, Rheasilvia was superimposed by several mid-sized impact craters. The most prominent craters are Tuccia, Eusebia, Vibidia, Galeria, and Antonia, whose geology and formation ages are investigated in detail in this work. These impact structures provide a variety of morphologies indicating different sorts of subsequent impact-related or gravity-driven mass wasting processes. Understanding the geologic history of the relatively young craters in the Rheasilvia basin is important in order to understand the even more degraded craters in other regions of Vesta.

In this paper we present a time-stratigraphic scheme and geologic time scale for the protoplanet Vesta, based on global geologic mapping and other analyses of NASA Dawn spacecraft data, complemented by insights gained from laboratory studies of howardite–eucrite–diogenite (HED) meteorites and geophysical modeling. On the basis of prominent impact structures and their associated deposits, we propose a time scale for Vesta that consists of four geologic time periods: Pre-Veneneian, Veneneian, Rheasilvian, and Marcian. The Pre-Veneneian Period covers the time from the formation of Vesta up to the Veneneia impact event, from 4.6 Ga to >2.1 Ga (using the asteroid flux-derived chronology system) or from 4.6 Ga to 3.7 Ga (under the lunar-derived chronology system). The Veneneian Period covers the time span between the Veneneia and Rheasilvia impact events, from >2.1 to 1 Ga (asteroid flux-derived chronology) or from 3.7 to 3.5 Ga (lunar-derived chronology), respectively. The Rheasilvian Period covers the time span between the Rheasilvia and Marcia impact events, and the Marcian Period covers the time between the Marcia impact event until the present. The age of the Marcia impact is still uncertain, but our current best estimates from crater counts of the ejecta blanket suggest an age between ∼120 and 390 Ma, depending upon choice of chronology system used. Regardless, the Marcia impact represents the youngest major geologic event on Vesta. Our proposed four-period geologic time scale for Vesta is, to a first order, comparable to those developed for other airless terrestrial bodies.

We report on a preliminary global geologic map of Vesta, based on data from the Dawn spacecraft’s High-Altitude Mapping Orbit (HAMO) and informed by Low-Altitude Mapping Orbit (LAMO) data. This map is part of an iterative mapping effort; the geologic map has been refined with each improvement in resolution. Vesta has a heavily-cratered surface, with large craters evident in numerous locations. The south pole is dominated by an impact structure identified before Dawn’s arrival. Two large impact structures have been resolved: the younger, larger Rheasilvia structure, and the older, more degraded Veneneia structure. The surface is also characterized by a system of deep, globe-girdling equatorial troughs and ridges, as well as an older system of troughs and ridges to the north. Troughs and ridges are also evident cutting across, and spiraling arcuately from, the Rheasilvia central mound.

However, no volcanic features have been unequivocally identified. Vesta can be divided very broadly into three terrains: heavily-cratered terrain; ridge-and-trough terrain (equatorial and northern); and terrain associated with the Rheasilvia crater. Localized features include bright and dark material and ejecta (some defined specifically by color); lobate deposits; and mass-wasting materials. No obvious volcanic features are evident. Stratigraphy of Vesta’s geologic units suggests a history in which formation of a primary crust was followed by the formation of impact craters, including Veneneia and the associated Saturnalia Fossae unit. Formation of Rheasilvia followed, along with associated structural deformation that shaped the Divalia Fossae ridge-and-trough unit at the equator. Subsequent impacts and mass wasting events subdued impact craters, rims and portions of ridge-and-trough sets, and formed slumps and landslides, especially within crater floors and along crater rims and scarps. Subsequent to the formation of Rheasilvia, discontinuous low-albedo deposits formed or were emplaced; these lie stratigraphically above the equatorial ridges that likely were formed by Rheasilvia. The last features to be formed were craters with bright rays and other surface mantling deposits.

Executed progressively throughout data acquisition, the iterative mapping process provided the team with geologic proto-units in a timely manner. However, interpretation of the resulting map was hampered by the necessity to provide the team with a standard nomenclature and symbology early in the process. With regard to mapping and interpreting units, the mapping process was hindered by the lack of calibrated mineralogic information. Topography and shadow played an important role in discriminating features and terrains, especially in the early stages of data acquisition.