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.

Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.

Gompertz’s empirical equation remains the most popular one in describing cancer cell population growth in a wide spectrum of bio-medical situations due to its good fit to data and simplicity. Many efforts were documented in the literature aimed at understanding the mechanisms that may support Gompertz’s elegant model equation. One of the most convincing efforts was carried out by Gyllenberg and Webb. They divide the cancer cell population into the proliferative cells and the quiescent cells. In their two dimensional model, the dead cells are assumed to be removed from the tumor instantly. In this paper, we modify their model by keeping track of the dead cells remaining in the tumor. We perform mathematical and computational studies on this three dimensional model and compare the model dynamics to that of the model of Gyllenberg and Webb. Our mathematical findings suggest that if an avascular tumor grows according to our three-compartment model, then as the death rate of quiescent cells decreases to zero, the percentage of proliferative cells also approaches to zero. Moreover, a slow dying quiescent population will increase the size of the tumor. On the other hand, while the tumor size does not depend on the dead cell removal rate, its early and intermediate growth stages are very sensitive to it.

We investigate near-field radiative heat transfer between Indium Tin Oxide (ITO) nanowire arrays which behave as type 1 and 2 hyperbolic metamaterials. Using spatial dispersion dependent effective medium theory to model the dielectric function of the nanowires, the impact of filling fraction on the heat transfer is analyzed. Depending on the filling fraction, it is possible to achieve both types of hyperbolic modes. At 150 nm vacuum gap, the heat transfer between the nanowires with 0.5 filling fraction can be 11 times higher than that between two bulk ITOs. For vacuum gaps less than 150 nm the heat transfer increases as the filling fraction decreases. Results obtained from this study will facilitate applications of ITO nanowires as hyperbolic metamaterials for energy systems.

A film-coupled metamaterial structure is numerically investigated for enhancing the light absorption in an ultrathin photovoltaic layer of crystalline gallium arsenide (GaAs). The top subwavelength concave grating and the bottom metallic film could not only effectively trap light with the help of wave interference and magnetic resonance effects excited above the bandgap, but also practically serve as electrical contacts for photon-generated charge collection. The energy absorbed by the active layer is greatly enhanced with the help of the film-coupled metamaterial structure, resulting in significant improvement on the short-circuit current density by three times over a free-standing GaAs layer at the same thickness. The performance of the proposed light trapping structure is demonstrated to be little affected by the grating ridge width considering the geometric tolerance during fabrication. The optical absorption at oblique incidences also shows direction-insensitive behavior, which is highly desired for efficiently converting off-normal sunlight to electricity. The results would facilitate the development of next-generation ultrathin solar cells with lower cost and higher efficiency.

In this work, we report the design of a wavelength-tunable infrared metamaterial by tailoring magnetic resonance condition with the phase transition of vanadium dioxide (VO₂). Numerical simulation based on the finite-difference time-domain method shows a broad absorption peak at the wavelength of 10.9 μm when VO₂ is a metal, but it shifts to 15.1 μm when VO₂ changes to dielectric phase below its phase transition temperature of 68 °C. The large tunability of 38.5% in the resonance wavelength stems from the different excitation conditions of magnetic resonance mediated by plasmon in metallic VO₂ but optical phonons in dielectric VO₂. The physical mechanism is elucidated with the aid of electromagnetic field distribution at the resonance wavelengths. A hybrid magnetic resonance mode due to the plasmon-phonon coupling is also discussed. The results here would be beneficial for active control of thermal radiation in novel electronic, optical, and thermal devices.

Proteins can exist as multiple proteoforms in vivo, as a result of alternative splicing and single-nucleotide polymorphisms (SNPs), as well as posttranslational processing. To address their clinical significance in a context of diagnostic information, proteoforms require a more in-depth analysis. Mass spectrometric immunoassays (MSIA) have been devised for studying structural diversity in human proteins. MSIA enables protein profiling in a simple and high-throughput manner, by combining the selectivity of targeted immunoassays, with the specificity of mass spectrometric detection. MSIA has been used for qualitative and quantitative analysis of single and multiple proteoforms, distinguishing between normal fluctuations and changes related to clinical conditions. This mini review offers an overview of the development and application of mass spectrometric immunoassays for clinical and population proteomics studies. Provided are examples of some recent developments, and also discussed are the trends and challenges in mass spectrometry-based immunoassays for the next-phase of clinical applications.

Background: While prior studies have quantified the mortality burden of the 1957 H2N2 influenza pandemic at broad geographic regions in the United States, little is known about the pandemic impact at a local level. Here we focus on analyzing the transmissibility and mortality burden of this pandemic in Arizona, a setting where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.

Methods: Using archival death certificates from 1954 to 1961, we quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 H2N2 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and assumed generation intervals of 3 and 4 days. Local newspaper articles published during 1957–1958 were also examined.

Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 16.59 in the elderly (≥65 years). All other age groups exhibit very low excess-mortality and the typical U-shaped age-pattern was absent. However, the standardized mortality ratio was greatest (4.06) among children and young adolescents (5–14 years) from October 1957-March 1958, based on mortality rates of respiratory deaths. Transmissibility was greatest during the same 1957–1958 period, when the mean reproduction number was estimated at 1.08–1.11, assuming 3- or 4-day generation intervals with exponential or fixed distributions.

Conclusions: Maricopa County exhibited very low mortality impact associated with the 1957 influenza pandemic. Understanding the relatively low excess-mortality rates and transmissibility in Maricopa County during this historic pandemic may help public health officials prepare for and mitigate future outbreaks of influenza.

Introduction: Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III_0a without glycosylation and apoC-III[subscript 0b] with glycosylation), monosialylated (apoC-III₁) or disialylated (apoC-III₂) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.

Methods: In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.

Results: Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III_0a, apoC-III_0b, and apoC-III₁ to apoC-III₂ were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (S[subscript i]). The relationship of apoC-III₁ / apoC-III₂ with S_i persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III_0a / apoC-III₂ (r = 0.47, p<0.001), apoC-III_0b / apoC-III₂ (r = 0.41, p<0.001), apoC-III₁ / apoC-III₂ (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III_0a (r = 0.57, p<0.001), apoC-III_0b (r = 0.56. p<0.001) and apoC-III₁ (r = 0.67, p<0.001), but not apoC-III₂ (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III₂ compared with the other proteoforms.

Conclusion: We conclude that apoC-III_0a, apoC-III_0b, and apoC-III₁, but not apoC-III₂ appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.

Background: On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness.

Methods: We used a Bayesian approach combined with a SEIR (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case data to assess the reproduction number (R) of A/H7N9 by province and to evaluate the impact of live bird market closures in April and May 2013. Simulation studies helped quantify the performance of our approach in the context of an emerging pathogen, where human-to-human transmission is limited and most cases arise from spillover events. We also used alternative approaches to estimate R based on individual-level information on prior exposure and compared the transmission potential of influenza A/H7N9 with that of other recent zoonoses.

Results: Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated transmission potential of A/H7N9 appears lower than that of recent zoonotic threats, including avian influenza A/H5N1, swine influenza H3N2sw and Nipah virus.

Conclusion: Although uncertainty remains high in R estimates for H7N9 due to limited epidemiological information, all available evidence points to a low transmission potential. Continued monitoring of the transmission potential of A/H7N9 is critical in the coming months as intervention measures may be relaxed and seasonal factors could promote disease transmission in colder months.