ASU Scholarship Showcase

Background: Emerging interventions that rely on and harness variability in behavior to adapt to individual performance over time may outperform interventions that prescribe static goals (e.g., 10,000 steps/day). The purpose of this factorial trial was to compare adaptive vs. static goal setting and immediate vs. delayed, non-contingent financial rewards for increasing free-living physical activity (PA).

Methods: A 4-month 2 × 2 factorial randomized controlled trial tested main effects for goal setting (adaptive vs. static goals) and rewards (immediate vs. delayed) and interactions between factors to increase steps/day as measured by a Fitbit Zip. Moderate-to-vigorous PA (MVPA) minutes/day was examined as a secondary outcome.

Results: Participants (N = 96) were mainly female (77%), aged 41 ± 9.5 years, and all were insufficiently active and overweight/obese (mean BMI = 34.1 ± 6.2). Participants across all groups increased by 2389 steps/day on average from baseline to intervention phase (p < .001). Participants receiving static goals showed a stronger increase in steps per day from baseline phase to intervention phase (2630 steps/day) than those receiving adaptive goals (2149 steps/day; difference = 482 steps/day, p = .095). Participants receiving immediate rewards showed stronger improvement (2762 step/day increase) from baseline to intervention phase than those receiving delayed rewards (2016 steps/day increase; difference = 746 steps/day, p = .009). However, the adaptive goals group showed a slower decrease in steps/day from the beginning of the intervention phase to the end of the intervention phase (i.e. less than half the rate) compared to the static goals group (−7.7 steps vs. -18.3 steps each day; difference = 10.7 steps/day, p < .001) resulting in better improvements for the adaptive goals group by study end. Rate of change over the intervention phase did not differ between reward groups. Significant goal phase x goal setting x reward interactions were observed.

Conclusions: Adaptive goals outperformed static goals (i.e., 10,000 steps) over a 4-month period. Small immediate rewards outperformed larger, delayed rewards. Adaptive goals with either immediate or delayed rewards should be preferred for promoting PA.

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.

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.

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.

A relatively unexplored issue in cybersecurity science and engineering is whether there exist intrinsic patterns of cyberattacks. Conventional wisdom favors absence of such patterns due to the overwhelming complexity of the modern cyberspace. Surprisingly, through a detailed analysis of an extensive data set that records the time-dependent frequencies of attacks over a relatively wide range of consecutive IP addresses, we successfully uncover intrinsic spatiotemporal patterns underlying cyberattacks, where the term “spatio” refers to the IP address space. In particular, we focus on analyzing macroscopic properties of the attack traffic flows and identify two main patterns with distinct spatiotemporal characteristics: deterministic and stochastic. Strikingly, there are very few sets of major attackers committing almost all the attacks, since their attack “fingerprints” and target selection scheme can be unequivocally identified according to the very limited number of unique spatiotemporal characteristics, each of which only exists on a consecutive IP region and differs significantly from the others. We utilize a number of quantitative measures, including the flux-fluctuation law, the Markov state transition probability matrix, and predictability measures, to characterize the attack patterns in a comprehensive manner. A general finding is that the attack patterns possess high degrees of predictability, potentially paving the way to anticipating and, consequently, mitigating or even preventing large-scale cyberattacks using macroscopic approaches.

Supply-demand processes take place on a large variety of real-world networked systems ranging from power grids and the internet to social networking and urban systems. In a modern infrastructure, supply-demand systems are constantly expanding, leading to constant increase in load requirement for resources and consequently, to problems such as low efficiency, resource scarcity, and partial system failures. Under certain conditions global catastrophe on the scale of the whole system can occur through the dynamical process of cascading failures. We investigate optimization and resilience of time-varying supply-demand systems by constructing network models of such systems, where resources are transported from the supplier sites to users through various links. Here by optimization we mean minimization of the maximum load on links, and system resilience can be characterized using the cascading failure size of users who fail to connect with suppliers.

We consider two representative classes of supply schemes: load driven supply and fix fraction supply. Our findings are: (1) optimized systems are more robust since relatively smaller cascading failures occur when triggered by external perturbation to the links; (2) a large fraction of links can be free of load if resources are directed to transport through the shortest paths; (3) redundant links in the performance of the system can help to reroute the traffic but may undesirably transmit and enlarge the failure size of the system; (4) the patterns of cascading failures depend strongly upon the capacity of links; (5) the specific location of the trigger determines the specific route of cascading failure, but has little effect on the final cascading size; (6) system expansion typically reduces the efficiency; and (7) when the locations of the suppliers are optimized over a long expanding period, fewer suppliers are required. These results hold for heterogeneous networks in general, providing insights into designing optimal and resilient complex supply-demand systems that expand constantly in time.

Previous proof-of-concept measurements on single-layer two-dimensional membrane-protein crystals performed at X-ray free-electron lasers (FELs) have demonstrated that the collection of meaningful diffraction patterns, which is not possible at synchrotrons because of radiation-damage issues, is feasible. Here, the results obtained from the analysis of a thousand single-shot, room-temperature X-ray FEL diffraction images from two-dimensional crystals of a bacteriorhodopsin mutant are reported in detail. The high redundancy in the measurements boosts the intensity signal-to-noise ratio, so that the values of the diffracted intensities can be reliably determined down to the detector-edge resolution of 4 Å. The results show that two-dimensional serial crystallography at X-ray FELs is a suitable method to study membrane proteins to near-atomic length scales at ambient temperature. The method presented here can be extended to pump–probe studies of optically triggered structural changes on submillisecond timescales in two-dimensional crystals, which allow functionally relevant large-scale motions that may be quenched in three-dimensional crystals.

Background: Advancements in geographic information systems over the past two decades have increased the specificity by which an individual’s neighborhood environment may be spatially defined for physical activity and health research. This study investigated how different types of street network buffering methods compared in measuring a set of commonly used built environment measures (BEMs) and tested their performance on associations with physical activity outcomes.

Methods: An internationally-developed set of objective BEMs using three different spatial buffering techniques were used to evaluate the relative differences in resulting explanatory power on self-reported physical activity outcomes. BEMs were developed in five countries using ‘sausage,’ ‘detailed-trimmed,’ and ‘detailed,’ network buffers at a distance of 1 km around participant household addresses (n = 5883).

Results: BEM values were significantly different (p < 0.05) for 96% of sausage versus detailed-trimmed buffer comparisons and 89% of sausage versus detailed network buffer comparisons. Results showed that BEM coefficients in physical activity models did not differ significantly across buffering methods, and in most cases BEM associations with physical activity outcomes had the same level of statistical significance across buffer types. However, BEM coefficients differed in significance for 9% of the sausage versus detailed models, which may warrant further investigation.

Conclusions: Results of this study inform the selection of spatial buffering methods to estimate physical activity outcomes using an internationally consistent set of BEMs. Using three different network-based buffering methods, the findings indicate significant variation among BEM values, however associations with physical activity outcomes were similar across each buffering technique. The study advances knowledge by presenting consistently assessed relationships between three different network buffer types and utilitarian travel, sedentary behavior, and leisure-oriented physical activity outcomes.

Background: The World Health Organization recommends strategies to improve urban design, public transportation, and recreation facilities to facilitate physical activity for non-communicable disease prevention for an increasingly urbanized global population. Most evidence supporting environmental associations with physical activity comes from single countries or regions with limited variation in urban form. This paper documents variation in comparable built environment features across countries from diverse regions.

Methods: The International Physical Activity and the Environment Network (IPEN) study of adults aimed to measure the full range of variation in the built environment using geographic information systems (GIS) across 12 countries on 5 continents. Investigators in Australia, Belgium, Brazil, Colombia, the Czech Republic, Denmark, China, Mexico, New Zealand, Spain, the United Kingdom, and the United States followed a common research protocol to develop internationally comparable measures. Using detailed instructions, GIS-based measures included features such as walkability (i.e., residential density, street connectivity, mix of land uses), and access to public transit, parks, and private recreation facilities around each participant’s residential address using 1-km and 500-m street network buffers.

Results: Eleven of 12 countries and 15 cities had objective GIS data on built environment features. We observed a 38-fold difference in median residential densities, a 5-fold difference in median intersection densities and an 18-fold difference in median park densities. Hong Kong had the highest and North Shore, New Zealand had the lowest median walkability index values, representing a difference of 9 standard deviations in GIS-measured walkability.

Conclusions: Results show that comparable measures can be created across a range of cultural settings revealing profound global differences in urban form relevant to physical activity. These measures allow cities to be ranked more precisely than previously possible. The highly variable measures of urban form will be used to explain individuals’ physical activity, sedentary behaviors, body mass index, and other health outcomes on an international basis. Present measures provide the ability to estimate dose–response relationships from projected changes to the built environment that would otherwise be impossible.