ASU Scholarship Showcase

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.

The effects of urbanization on ozone levels have been widely investigated over cities primarily located in temperate and/or humid regions. In this study, nested WRF-Chem simulations with a finest grid resolution of 1 km are conducted to investigate ozone concentrations O₃ due to urbanization within cities in arid/semi-arid environments. First, a method based on a shape preserving Monotonic Cubic Interpolation (MCI) is developed and used to downscale anthropogenic emissions from the 4 km resolution 2005 National Emissions Inventory (NEI05) to the finest model resolution of 1 km. Using the rapidly expanding Phoenix metropolitan region as the area of focus, we demonstrate the proposed MCI method achieves ozone simulation results with appreciably improved correspondence to observations relative to the default interpolation method of the WRF-Chem system. Next, two additional sets of experiments are conducted, with the recommended MCI approach, to examine impacts of urbanization on ozone production: (1) the urban land cover is included (i.e., urbanization experiments) and, (2) the urban land cover is replaced with the region's native shrubland. Impacts due to the presence of the built environment on O₃ are highly heterogeneous across the metropolitan area. Increased near surface O₃ due to urbanization of 10–20 ppb is predominantly a nighttime phenomenon while simulated impacts during daytime are negligible. Urbanization narrows the daily O₃ range (by virtue of increasing nighttime minima), an impact largely due to the region's urban heat island. Our results demonstrate the importance of the MCI method for accurate representation of the diurnal profile of ozone, and highlight its utility for high-resolution air quality simulations for urban areas.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

An interesting occurrence of a Rossby wave breaking event observed during the VORCORE experiment is presented and explained. Twenty-seven balloons were launched inside the Antarctic polar vortex. Almost all of these balloons evolved in the stratosphere around 500K within the vortex, except the one launched on 28 October 2005. In this case, the balloon was caught within a tongue of high potential vorticity (PV), and was ejected from the polar vortex. The evolution of this event is studied for the period between 19 and 25 November 2005. It is found that at the beginning of this period, the polar vortex experienced distortions due to the presence of Rossby waves. Then, these waves break and a tongue of high PV develops. On 25 November, the tongue became separated from the vortex and the balloon was ejected into the surf zone. Lagrangian simulations demonstrate that the air masses surrounding the balloon after its ejection were originating from the vortex edge. The wave breaking and the development of the tongue are confined within a region where a planetary Quasi-Stationary Wave 1 (QSW1) induces wind speeds with weaker values. The QSW1 causes asymmetry in the wind speed and the horizontal PV gradient along the edge of the polar vortex, resulting in a localized jet. Rossby waves with smaller scales propagating on top of this jet amplify as they enter the jet exit region and then break. The role of the QSW1 on the formation of the weak flow conditions that caused the non-linear wave breaking observed near the vortex edge is confirmed by three-dimensional numerical simulations using forcing with and without the contribution of the QSW1.

Background: A limitation of traditional outcome studies from behavioral interventions is the lack of attention given to evaluating the influence of moderating variables. This study examined possible moderation effect of baseline activity levels on physical activity change as a result of the Ready for Recess intervention.

Methods: Ready for Recess (August 2009-September 2010) was a controlled trial with twelve schools randomly assigned to one of four conditions: control group, staff supervision, equipment availability, and the combination of staff supervision and equipment availability. A total of 393 children (181 boys and 212 girls) from grades 3 through 6 (8–11 years old) were asked to wear an Actigraph monitor during school time on 4–5 days of the week. Assessments were conducted at baseline (before intervention) and post intervention (after intervention).

Results: Initial MVPA moderated the effect of Staff supervision (β = −0.47%; p < .05), but not Equipment alone and Staff + Equipment (p > .05). Participants in the Staff condition that were 1 standard deviation (SD) below the mean for baseline MVPA (classified as “low active”) had lower MVPA levels at post-intervention when compared with their low active peers in the control condition (Mean_diff = −10.8 ± 2.9%; p = .005). High active individuals (+1SD above the mean) in the Equipment treatment also had lower MVPA values at post-intervention when compared with their highly active peers in the control group (Mean_diff = −9.5 ± 2.9%; p = .009).

Conclusions: These results indicate that changes in MVPA levels at post-intervention were reduced in highly active participants when recess staff supervision was provided. In this study, initial MVPA moderated the effect of Staff supervision on children’s MVPA after 6 months of intervention. Staff training should include how to work with inactive youth but also how to assure that active children remain active.

Background: In the United States, approximately one in 110 pregnancies end in stillbirth affecting more than 26,000 women annually. Women experiencing stillbirth have a threefold greater risk of developing depressive symptoms compared to women experiencing live birth. Depression contributes negatively to health outcomes for both mothers and babies subsequent to stillbirth. Physical activity may improve depression in these women, however, little is known about acceptable physical activity interventions for women after stillbirth. This is the purpose of this descriptive exploratory study.

Methods: Eligible women were between ages 19 and 45, and experienced stillbirth within one year of the study. An online survey was used to ask questions related to 1) pregnancy and family information (i.e., time since stillbirth, weight gain during pregnancy, number of other children) 2) physical activity participation, 3) depressive symptomatology, and 4) demographics.

Results: One hundred seventy-five women participated in the study (M age = 31.26 ± 5.52). Women reported participating in regular physical activity (at least 150 minutes of moderate activity weekly) before (60%) and during (47%) their pregnancy, as well as after their stillbirth (61%). Only 37% were currently meeting physical activity recommendations. Approximately 88% reported depression (i.e., score of >10 on depression scale). When asked how women cope with depression, anxiety, or grief, 38% said physical activity. Of those that reported using physical activity to cope after stillbirth, they did so to help with depression (58%), weight loss (55%), and better overall physical health (52%). To cope with stillbirth, women used walking (67%), followed by jogging (35%), and yoga (23%). Women who participated in physical activity after stillbirth reported significantly lower depressive symptoms (M = 15.10, SD = 5.32) compared to women who did not participate in physical activity (M = 18.06, SD = 5.57; t = -3.45, p = .001).

Conclusions: Physical activity may serve as a unique opportunity to help women cope with the multiple mental sequelae after stillbirth. This study provides data to inform healthcare providers about the potential role of physical activity in bereavement and recovery for women who have experienced stillbirth. Additional research is necessary in this vulnerable population.

Background: The transition to parenthood is consistently associated with declines in physical activity. In particular, working parents are at risk for inactivity, but research exploring physical activity barriers and facilitators in this population has been scarce. The purpose of this study was to qualitatively examine perceptions of physical activity among working parents.

Methods: Working mothers (n = 13) and fathers (n = 12) were recruited to participate in one of four focus group sessions and discuss physical activity barriers and facilitators. Data were analyzed using immersion/crystallization in NVivo 10.

Results: Major themes for barriers included family responsibilities, guilt, lack of support, scheduling constraints, and work. Major themes for facilitators included being active with children or during children’s activities, being a role model for children, making time/prioritizing, benefits to health and family, and having support available. Several gender differences emerged within each theme, but overall both mothers and fathers reported their priorities had shifted to focus on family after becoming parents, and those who were fitting in physical activity had developed strategies that allowed them to balance their household and occupational responsibilities.

Conclusions: The results of this study suggest working mothers and fathers report similar physical activity barriers and facilitators and would benefit from interventions that teach strategies for overcoming barriers and prioritizing physical activity amidst the demands of parenthood. Future interventions might consider targeting mothers and fathers in tandem to create an optimally supportive environment in the home.

Physical mechanisms of incongruency between observations and Weather Research and Forecasting (WRF) Model predictions are examined. Limitations of evaluation are constrained by (i) parameterizations of model physics, (ii) parameterizations of input data, (iii) model resolution, and (iv) flux observation resolution. Observations from a new 22.1-m flux tower situated within a residential neighborhood in Phoenix, Arizona, are utilized to evaluate the ability of the urbanized WRF to resolve finescale surface energy balance (SEB) when using the urban classes derived from the 30-m-resolution National Land Cover Database. Modeled SEB response to a large seasonal variation of net radiation forcing was tested during synoptically quiescent periods of high pressure in winter 2011 and premonsoon summer 2012. Results are presented from simulations employing five nested domains down to 333-m horizontal resolution. A comparative analysis of model cases testing parameterization of physical processes was done using four configurations of urban parameterization for the bulk urban scheme versus three representations with the Urban Canopy Model (UCM) scheme, and also for two types of planetary boundary layer parameterization: the local Mellor–Yamada–Janjić scheme and the nonlocal Yonsei University scheme. Diurnal variation in SEB constituent fluxes is examined in relation to surface-layer stability and modeled diagnostic variables. Improvement is found when adapting UCM for Phoenix with reduced errors in the SEB components. Finer model resolution is seen to have insignificant (<1 standard deviation) influence on mean absolute percent difference of 30-min diurnal mean SEB terms.