Open Access Publishing Fund

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https://hdl.handle.net/1805/6519

The IUPUI Open Access Fund underwrites reasonable publication charges for articles published in fee-based, peer-reviewed journals that are openly accessible. This fund addresses changes in scholarly communications while increasing the impact of and access to scholarship created by IUPUI faculty. Learn more at: https://library.indianapolis.iu.edu/digitalscholarship/oa/fund-oa

Annual reports on the progress of the fund are available from: https://scholarworks.indianapolis.iu.edu/handle/1805/11935

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Mandates and the Contributions of Open Genomic Data
(2013-10-14) Xia, Jingfeng
This research attempts to seek changing patterns of raw data availability and their correlations with implementations of open mandate policies. With a list of 13,785 journal articles whose authors archived datasets in a popular biomedical data repository after these articles were published in journals, this research uses regression analysis to test the correlations between data contributions and mandate implementations. It finds that both funder-based and publisher-based mandates have a strong impact on scholars’ likelihood to contribute to open data repositories. Evidence also suggests that like policies have changed the habit of authors in selecting publishing venues: open access journals have been apparently preferred by those authors whose projects are sponsored by the federal government agencies, and these journals are also highly ranked in the biomedical fields. Various stakeholders, particularly institutional administrators and open access professionals, may find the findings of this research helpful for adjusting data management policies to increase the number of quality free datasets and enhance data usability. The data-sharing example in biomedical studies provides a good case to show the importance of policy-making in the reshaping of scholarly communication.
Adolescent Health-Risk Behavior and Community Disorder
(2013-11) Wiehe, Sarah E.; Kwan, Mei-Po; Wilson, Jeffrey S.; Fortenberry, J. Dennis
Background Various forms of community disorder are associated with health outcomes but little is known about how dynamic context where an adolescent spends time relates to her health-related behaviors. Objective Assess whether exposure to contexts associated with crime (as a marker of community disorder) correlates with self-reported health-related behaviors among adolescent girls. Methods Girls (N = 52), aged 14–17, were recruited from a single geographic urban area and monitored for 1 week using a GPS-enabled cell phone. Adolescents completed an audio computer-assisted self-administered interview survey on substance use (cigarette, alcohol, or marijuana use) and sexual intercourse in the last 30 days. In addition to recorded home and school address, phones transmitted location data every 5 minutes (path points). Using ArcGIS, we defined community disorder as aggregated point-level Unified Crime Report data within a 200-meter Euclidian buffer from home, school and each path point. Using Stata, we analyzed how exposures to areas of higher crime prevalence differed among girls who reported each behavior or not. Results Participants lived and spent time in areas with variable crime prevalence within 200 meters of their home, school and path points. Significant differences in exposure occurred based on home location among girls who reported any substance use or not (p 0.04) and sexual intercourse or not (p 0.01). Differences in exposure by school and path points were only significant among girls reporting any substance use or not (p 0.03 and 0.02, respectively). Exposure also varied by school/non-school day as well as time of day. Conclusions Adolescent travel patterns are not random. Furthermore, the crime context where an adolescent spends time relates to her health-related behavior. These data may guide policy relating to crime control and inform time- and space-specific interventions to improve adolescent health.
The effects of uncertainty under a cap-and-trade policy on afforestation in the United States
(2013-10-30) Dumortier, Jerome
To combat climate change, cap-and-trade policies have been proposed and implemented in countries around the world. The stochastic carbon price that results from a cap-and-trade policy makes investment decisions in carbon mitigating and sequestering practices more complex. This letter illustrates the consequence of uncertainty by analyzing forest carbon offset credits under a potential cap-and-trade policy in the United States. The effects of uncertainty on afforestation, carbon sequestration, cropland allocation, and commodity prices using a real option framework are assessed. When compared with deterministic models, less land gets converted from cropland to forestry over the projection period of 40 years because landowners ﬁnd it optimal to wait before changing land-use to gain more information about the carbon price evolution. The simulation shows that most afforestation occurs in the south and the northeast with almost no conversion in the Corn Belt. The lesson for policy makers is that under carbon price uncertainty, lower afforestation and carbon sequestration takes place. To foster afforestation, mechanisms are necessary to reduce uncertainty at the expense of higher commodity prices.
Chaos and Robustness in a Single Family of Genetic Oscillatory Networks
(2014-03) Fu, Daniel; Tan, Patrick; Kuznetsov, Alexey; Molkov, Yaroslav I
Genetic oscillatory networks can be mathematically modeled with delay differential equations (DDEs). Interpreting genetic networks with DDEs gives a more intuitive understanding from a biological standpoint. However, it presents a problem mathematically, for DDEs are by construction infinitely-dimensional and thus cannot be analyzed using methods common for systems of ordinary differential equations (ODEs). In our study, we address this problem by developing a method for reducing infinitely-dimensional DDEs to two- and three-dimensional systems of ODEs. We find that the three-dimensional reductions provide qualitative improvements over the two-dimensional reductions. We find that the reducibility of a DDE corresponds to its robustness. For non-robust DDEs that exhibit high-dimensional dynamics, we calculate analytic dimension lines to predict the dependence of the DDEs’ correlation dimension on parameters. From these lines, we deduce that the correlation dimension of non-robust DDEs grows linearly with the delay. On the other hand, for robust DDEs, we find that the period of oscillation grows linearly with delay. We find that DDEs with exclusively negative feedback are robust, whereas DDEs with feedback that changes its sign are not robust. We find that non-saturable degradation damps oscillations and narrows the range of parameter values for which oscillations exist. Finally, we deduce that natural genetic oscillators with highly-regular periods likely have solely negative feedback.
Dissecting the expression landscape of RNA-binding proteins in human cancers
(2014-01) Kechavarzi, Bobak; Janga, Sarath Chandra
Background RNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level. Results We explore the expression of more than 800 RBPs in sixteen healthy human tissues and their patterns of dysregulation in cancer genomes from The Cancer Genome Atlas project. We show that genes encoding RBPs are consistently and significantly highly expressed compared with other classes of genes, including those encoding regulatory components such as transcription factors, miRNAs and long non-coding RNAs. We also demonstrate that a set of RBPs, numbering approximately 30, are strongly upregulated (SUR) across at least two-thirds of the nine cancers profiled in this study. Analysis of the protein–protein interaction network properties for the SUR and non-SUR groups of RBPs suggests that path length distributions between SUR RBPs is significantly lower than those observed for non-SUR RBPs. We further find that the mean path lengths between SUR RBPs increases in proportion to their contribution to prognostic impact. We also note that RBPs exhibiting higher variability in the extent of dysregulation across breast cancer patients have a higher number of protein–protein interactions. We propose that fluctuating RBP levels might result in an increase in non-specific protein interactions, potentially leading to changes in the functional consequences of RBP binding. Finally, we show that the expression variation of a gene within a patient group is inversely correlated with prognostic impact. Conclusions Overall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.
Cortical Bone Mechanical Properties Are Altered in an Animal Model of Progressive Chronic Kidney Disease
(2014-06) Newman, Christopher L.; Moe, Sharon M.; Chen, Neal X.; Hammond, Max A.; Wallace, Joseph M.; Nyman, Jeffry S.; Allen, Matthew R.
Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (~75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD.
Low Levels of p53 Protein and Chromatin Silencing of p53 Target Genes Repress Apoptosis in Drosophila Endocycling Cells
(2014-09) Zhang, Bingqing; Mehrotra, Sonam; Ng, Wei Lun; Calvi, Brian R
Apoptotic cell death is an important response to genotoxic stress that prevents oncogenesis. It is known that tissues can differ in their apoptotic response, but molecular mechanisms are little understood. Here, we show that Drosophila polyploid endocycling cells (G/S cycle) repress the apoptotic response to DNA damage through at least two mechanisms. First, the expression of all the Drosophila p53 protein isoforms is strongly repressed at a post-transcriptional step. Second, p53-regulated pro-apoptotic genes are epigenetically silenced in endocycling cells, preventing activation of a paused RNA Pol II by p53-dependent or p53-independent pathways. Over-expression of the p53A isoform did not activate this paused RNA Pol II complex in endocycling cells, but over-expression of the p53B isoform with a longer transactivation domain did, suggesting that dampened p53B protein levels are crucial for apoptotic repression. We also find that the p53A protein isoform is ubiquitinated and degraded by the proteasome in endocycling cells. In mitotic cycling cells, p53A was the only isoform expressed to detectable levels, and its mRNA and protein levels increased after irradiation, but there was no evidence for an increase in protein stability. However, our data suggest that p53A protein stability is regulated in unirradiated cells, which likely ensures that apoptosis does not occur in the absence of stress. Without irradiation, both p53A protein and a paused RNA pol II were pre-bound to the promoters of pro-apoptotic genes, preparing mitotic cycling cells for a rapid apoptotic response to genotoxic stress. Together, our results define molecular mechanisms by which different cells in development modulate their apoptotic response, with broader significance for the survival of normal and cancer polyploid cells in mammals.
Short-term Changes in Ambient Particulate Matter and Risk of Stroke: A Systematic Review and Meta-analysis
(2014-08) Wang, Yi; Eliot, Melissa N.; Wellenius, Gregory A.
Background Stroke is a leading cause of death and long‐term disability in the United States. There is a well‐documented association between ambient particulate matter air pollution (PM) and cardiovascular disease morbidity and mortality. Given the pathophysiologic mechanisms of these effects, short‐term elevations in PM may also increase the risk of ischemic and/or hemorrhagic stroke morbidity and mortality, but the evidence has not been systematically reviewed. Methods and Results We provide a comprehensive review of all observational human studies (January 1966 to January 2014) on the association between short‐term changes in ambient PM levels and cerebrovascular events. We also performed meta‐analyses to evaluate the evidence for an association between each PM size fraction (PM2.5, PM10, PM2.5‐10) and each outcome (total cerebrovascular disease, ischemic stroke/transient ischemic attack, hemorrhagic stroke) separately for mortality and hospital admission. We used a random‐effects model to estimate the summary percent change in relative risk of the outcome per 10‐μg/m3 increase in PM. Conclusions We found that PM2.5 and PM10 are associated with a 1.4% (95% CI 0.9% to 1.9%) and 0.5% (95% CI 0.3% to 0.7%) higher total cerebrovascular disease mortality, respectively, with evidence of inconsistent, nonsignificant associations for hospital admission for total cerebrovascular disease or ischemic or hemorrhagic stroke. Current limited evidence does not suggest an association between PM2.5‐10 and cerebrovascular mortality or morbidity. We discuss the potential sources of variability in results across studies, highlight some observations, and identify gaps in literature and make recommendations for future studies.
A Closed-Loop Model of the Respiratory System: Focus on Hypercapnia and Active Expiration
(2014-10) Molkov, Yaroslav I; Shevtsova, Natalia A; Park, Choongseok; Ben-Tal, Alona; Smith, Jeffrey C; Rubin, Jonathan E; Rybak, Ilya A
Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal “expiratory” muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.
Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
(2014-06) Corson, Timothy W.; Samuels, Brian C; Wenzel, Andrea A; Geary, Anna J; Riley, Amanda A; McCarthy, Brian P; Hanenberg, Helmut; Bailey, Barbara J; Rogers, Pamela I; Pollok, Karen E; Rajashekhar, Gangaraju; Territo, Paul R
Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ( F) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed F, as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, F in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of F modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future.

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