ASU Scholarship Showcase

We present results from experiments at the Linac Coherent Light Source (LCLS) demonstrating that serial femtosecond crystallography (SFX) can be performed to high resolution (~2.5 Å) using protein microcrystals deposited on an ultra-thin silicon nitride membrane and embedded in a preservation medium at room temperature. Data can be acquired at a high acquisition rate using x-ray free electron laser sources to overcome radiation damage, while sample consumption is dramatically reduced compared to flowing jet methods. We achieved a peak data acquisition rate of 10 Hz with a hit rate of ~38%, indicating that a complete data set could be acquired in about one 12-hour LCLS shift using the setup described here, or in even less time using hardware optimized for fixed target SFX. This demonstration opens the door to ultra low sample consumption SFX using the technique of diffraction-before-destruction on proteins that exist in only small quantities and/or do not produce the copious quantities of microcrystals required for flowing jet methods.

Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth’s oxygenic atmosphere. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S₀ to S₄, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S₁ state and after double laser excitation (putative S₃ state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn₄CaO₅ core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the ‘dangler’ Mn) and the Mn₃CaO_x cubane in the S₂ to S₃ transition, as predicted by spectroscopic and computational studies. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.

It has been suggested that the extended intensity profiles surrounding Bragg reflections that arise when a series of finite crystals of varying size and shape are illuminated by the intense, coherent illumination of an x-ray free-electron laser may enable the crystal’s unit-cell electron density to be obtained ab initio via well-established iterative phasing algorithms. Such a technique could have a significant impact on the field of biological structure determination since it avoids the need for a priori information from similar known structures, multiple measurements near resonant atomic absorption energies, isomorphic derivative crystals, or atomic-resolution data. Here, we demonstrate this phasing technique on diffraction patterns recorded from artificial two-dimensional microcrystals using the seeded soft x-ray free-electron laser FERMI. We show that the technique is effective when the illuminating wavefront has nonuniform phase and amplitude, and when the diffraction intensities cannot be measured uniformly throughout reciprocal space because of a limited signal-to-noise ratio.

The City of Phoenix (Arizona, USA) developed a Tree and Shade Master Plan and a Cool Roofs initiative to ameliorate extreme heat during the summer months in their arid city. This study investigates the impact of the City's heat mitigation strategies on daytime microclimate for a pre-monsoon summer day under current climate conditions and two climate change scenarios. We assessed the cooling effect of trees and cool roofs in a Phoenix residential neighborhood using the microclimate model ENVI-met. First, using xeric landscaping as a base, we created eight tree planting scenarios (from 0% canopy cover to 30% canopy cover) for the neighborhood to characterize the relationship between canopy cover and daytime cooling benefit of trees. In a second set of simulations, we ran ENVI-met for nine combined tree planting and landscaping scenarios (mesic, oasis, and xeric) with regular roofs and cool roofs under current climate conditions and two climate change projections. For each of the 54 scenarios, we compared average neighborhood mid-afternoon air temperatures and assessed the benefits of each heat mitigation measure under current and projected climate conditions. Findings suggest that the relationship between percent canopy cover and air temperature reduction is linear, with 0.14 °C cooling per percent increase in tree cover for the neighborhood under investigation. An increase in tree canopy cover from the current 10% to a targeted 25% resulted in an average daytime cooling benefit of up to 2.0 °C in residential neighborhoods at the local scale. Cool roofs reduced neighborhood air temperatures by 0.3 °C when implemented on residential homes. The results from this city-specific mitigation project will inform messaging campaigns aimed at engaging the city decision makers, industry, and the public in the green building and urban forestry initiatives.

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.

Shade plays an important role in designing pedestrian-friendly outdoor spaces in hot desert cities. This study investigates the impact of photovoltaic canopy shade and tree shade on thermal comfort through meteorological observations and field surveys at a pedestrian mall on Arizona State University's Tempe campus. During the course of 1 year, on selected clear calm days representative of each season, we conducted hourly meteorological transects from 7:00 a.m. to 6:00 p.m. and surveyed 1284 people about their thermal perception, comfort, and preferences. Shade lowered thermal sensation votes by approximately 1 point on a semantic differential 9-point scale, increasing thermal comfort in all seasons except winter. Shade type (tree or solar canopy) did not significantly impact perceived comfort, suggesting that artificial and natural shades are equally efficient in hot dry climates. Globe temperature explained 51 % of the variance in thermal sensation votes and was the only statistically significant meteorological predictor. Important non-meteorological factors included adaptation, thermal comfort vote, thermal preference, gender, season, and time of day. A regression of subjective thermal sensation on physiological equivalent temperature yielded a neutral temperature of 28.6 °C. The acceptable comfort range was 19.1 °C-38.1 °C with a preferred temperature of 20.8 °C. Respondents exposed to above neutral temperature felt more comfortable if they had been in air-conditioning 5 min prior to the survey, indicating a lagged response to outdoor conditions. Our study highlights the importance of active solar access management in hot urban areas to reduce thermal stress.

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.

Background: The Nike + Fuelband is a commercially available, wrist-worn accelerometer used to track physical activity energy expenditure (PAEE) during exercise. However, validation studies assessing the accuracy of this device for estimating PAEE are lacking. Therefore, this study examined the validity and reliability of the Nike + Fuelband for estimating PAEE during physical activity in young adults. Secondarily, we compared PAEE estimation of the Nike + Fuelband with the previously validated SenseWear Armband (SWA).

Methods: Twenty-four participants (n = 24) completed two, 60-min semi-structured routines consisting of sedentary/light-intensity, moderate-intensity, and vigorous-intensity physical activity. Participants wore a Nike + Fuelband and SWA, while oxygen uptake was measured continuously with an Oxycon Mobile (OM) metabolic measurement system (criterion).

Results: The Nike + Fuelband (ICC = 0.77) and SWA (ICC = 0.61) both demonstrated moderate to good validity. PAEE estimates provided by the Nike + Fuelband (246 ± 67 kcal) and SWA (238 ± 57 kcal) were not statistically different than OM (243 ± 67 kcal). Both devices also displayed similar mean absolute percent errors for PAEE estimates (Nike + Fuelband = 16 ± 13 %; SWA = 18 ± 18 %). Test-retest reliability for PAEE indicated good stability for Nike + Fuelband (ICC = 0.96) and SWA (ICC = 0.90).

Conclusion: The Nike + Fuelband provided valid and reliable estimates of PAEE, that are similar to the previously validated SWA, during a routine that included approximately equal amounts of sedentary/light-, moderate- and vigorous-intensity physical activity.

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.