ASU Scholarship Showcase

This study investigates the impact of urban form and landscaping type on the mid-afternoon microclimate in semi-arid Phoenix, Arizona. The goal is to find effective urban form and design strategies to ameliorate temperatures during the summer months. We simulated near-ground air temperatures for typical residential neighborhoods in Phoenix using the three-dimensional microclimate model ENVI-met. The model was validated using weather observations from the North Desert Village (NDV) landscape experiment, located on the Arizona State University's Polytechnic campus. The NDV is an ideal site to determine the model's input parameters, since it is a controlled environment recreating three prevailing residential landscape types in the Phoenix metropolitan area (mesic, oasis, and xeric). After validation, we designed five neighborhoods with different urban forms that represent a realistic cross-section of typical residential neighborhoods in Phoenix. The scenarios follow the Local Climate Zone (LCZ) classification scheme after Stewart and Oke. We then combined the neighborhoods with three landscape designs and, using ENVI-met, simulated microclimate conditions for these neighborhoods for a typical summer day. Results were analyzed in terms of mid-afternoon air temperature distribution and variation, ventilation, surface temperatures, and shading. Findings show that advection is important for the distribution of within-design temperatures and that spatial differences in cooling are strongly related to solar radiation and local shading patterns. In mid-afternoon, dense urban forms can create local cool islands. Our approach suggests that the LCZ concept is useful for planning and design purposes.

Summer daytime cooling efficiency of various land cover is investigated for the urban core of Phoenix, Arizona, using the Local-Scale Urban Meteorological Parameterization Scheme (LUMPS). We examined the urban energy balance for 2 summer days in 2005 to analyze the daytime cooling-water use tradeoff and the timing of sensible heat reversal at night. The plausibility of the LUMPS model results was tested using remotely sensed surface temperatures from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) imagery and reference evapotranspiration values from a meteorological station. Cooling efficiency was derived from sensible and latent heat flux differences. The time when the sensible heat flux turns negative (sensible heat flux transition) was calculated from LUMPS simulated hourly fluxes. Results indicate that the time when the sensible heat flux changes direction at night is strongly influenced by the heat storage capacity of different land cover types and by the amount of vegetation. Higher heat storage delayed the transition up to 3 h in the study area, while vegetation expedited the sensible heat reversal by 2 h. Cooling efficiency index results suggest that overall, the Phoenix urban core is slightly more efficient at cooling than the desert, but efficiencies do not increase much with wet fractions higher than 20%. Industrial sites with high impervious surface cover and low wet fraction have negative cooling efficiencies. Findings indicate that drier neighborhoods with heterogeneous land uses are the most efficient landscapes in balancing cooling and water use in Phoenix. However, further factors such as energy use and human vulnerability to extreme heat have to be considered in the cooling-water use tradeoff, especially under the uncertainties of future climate change.

Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients.

Methods: A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs.

Results: Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis.

Conclusion: The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

Background: Salmonella has been employed to deliver therapeutic molecules against cancer and infectious diseases. As the carrier for target gene(s), the cargo plasmid should be stable in the bacterial vector. Plasmid recombination has been reduced in E. coli by mutating several genes including the recA, recE, recF and recJ. However, to our knowledge, there have been no published studies of the effect of these or any other genes that play a role in plasmid recombination in Salmonella enterica.

Results: The effect of recA, recF and recJ deletions on DNA recombination was examined in three serotypes of Salmonella enterica. We found that (1) intraplasmid recombination between direct duplications was RecF-independent in Typhimurium and Paratyphi A, but could be significantly reduced in Typhi by a ΔrecA or ΔrecF mutation; (2) in all three Salmonella serotypes, both ΔrecA and ΔrecF mutations reduced intraplasmid recombination when a 1041 bp intervening sequence was present between the duplications; (3) ΔrecA and ΔrecF mutations resulted in lower frequencies of interplasmid recombination in Typhimurium and Paratyphi A, but not in Typhi; (4) in some cases, a ΔrecJ mutation could reduce plasmid recombination but was less effective than ΔrecA and ΔrecF mutations. We also examined chromosome-related recombination. The frequencies of intrachromosomal recombination and plasmid integration into the chromosome were 2 and 3 logs lower than plasmid recombination frequencies in Rec[superscript +] strains. A ΔrecA mutation reduced both intrachromosomal recombination and plasmid integration frequencies.

Conclusions: The ΔrecA and ΔrecF mutations can reduce plasmid recombination frequencies in Salmonella enterica, but the effect can vary between serovars. This information will be useful for developing Salmonella delivery vectors able to stably maintain plasmid cargoes for vaccine development and gene therapy.

Salmonella enterica serovar Typhimurium strains belonging to sequence type ST313 are a major cause of fatal bacteremia among HIV-infected adults and children in sub-Saharan Africa. Unlike “classical” non-typhoidal Salmonella (NTS), gastroenteritis is often absent during ST313 infections and isolates are most commonly recovered from blood, rather than from stool. This is consistent with observations in animals, in which ST313 strains displayed lower levels of intestinal colonization and higher recovery from deeper tissues relative to classic NTS isolates. A better understanding of the key environmental factors regulating these systemic infections is urgently needed. Our previous studies using dynamic Rotating Wall Vessel (RWV) bioreactor technology demonstrated that physiological levels of fluid shear regulate virulence, gene expression, and stress response profiles of classic S. Typhimurium. Here we provide the first demonstration that fluid shear alters the virulence potential and pathogenesis-related stress responses of ST313 strain D23580 in a manner that differs from classic NTS.

We quantified the spatio-temporal patterns of land cover/land use (LCLU) change to document and evaluate the daytime surface urban heat island (SUHI) for five hot subtropical desert cities (Beer Sheva, Israel; Hotan, China; Jodhpur, India; Kharga, Egypt; and Las Vegas, NV, USA). Sequential Landsat images were acquired and classified into the USGS 24-category Land Use Categories using object-based image analysis with an overall accuracy of 80% to 95.5%. We estimated the land surface temperature (LST) of all available Landsat data from June to August for years 1990, 2000, and 2010 and computed the urban-rural difference in the average LST and Normalized Difference Vegetation Index (NDVI) for each city. Leveraging non-parametric statistical analysis, we also investigated the impacts of city size and population on the urban-rural difference in the summer daytime LST and NDVI. Urban expansion is observed for all five cities, but the urbanization pattern varies widely from city to city. A negative SUHI effect or an oasis effect exists for all the cities across all three years, and the amplitude of the oasis effect tends to increase as the urban-rural NDVI difference increases. A strong oasis effect is observed for Hotan and Kharga with evidently larger NDVI difference than the other cities. Larger cities tend to have a weaker cooling effect while a negative association is identified between NDVI difference and population. Understanding the daytime oasis effect of desert cities is vital for sustainable urban planning and the design of adaptive management, providing valuable guidelines to foster smart desert cities in an era of climate variability, uncertainty, and change.

The Sky View Factor (SVF) is a dimension-reduced representation of urban form and one of the major variables in radiation models that estimate outdoor thermal comfort. Common ways of retrieving SVFs in urban environments include capturing fisheye photographs or creating a digital 3D city or elevation model of the environment. Such techniques have previously been limited due to a lack of imagery or lack of full scale detailed models of urban areas. We developed a web based tool that automatically generates synthetic hemispherical fisheye views from Google Earth at arbitrary spatial resolution and calculates the corresponding SVFs through equiangular projection. SVF results were validated using Google Maps Street View and compared to results from other SVF calculation tools. We generated 5-meter resolution SVF maps for two neighborhoods in Phoenix, Arizona to illustrate fine-scale variations of intra-urban horizon limitations due to urban form and vegetation. To demonstrate the utility of our synthetic fisheye approach for heat stress applications, we automated a radiation model to generate outdoor thermal comfort maps for Arizona State University’s Tempe campus for a hot summer day using synthetic fisheye photos and on-site meteorological data. Model output was tested against mobile transect measurements of the six-directional radiant flux density. Based on the thermal comfort maps, we implemented a pedestrian routing algorithm that is optimized for distance and thermal comfort preferences. Our synthetic fisheye approach can help planners assess urban design and tree planting strategies to maximize thermal comfort outcomes and can support heat hazard mitigation in urban areas.

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complex to modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection.