1,721,129 research outputs found
Microbiome
Each day people are exposed to millions of bioaerosols, including whole microorganisms, which can have both beneficial and detrimental effects. The next chapter in understanding the airborne microbiome of the built environment is characterizing the various sources of airborne microorganisms and the relative contribution of each. We have identified the following eight major categories of sources of airborne bacteria, viruses, and fungi in the built environment: humans; pets; plants; plumbing systems; heating, ventilation, and air-conditioning systems; mold; dust resuspension; and the outdoor environment. Certain species are associated with certain sources, but the full potential of source characterization and source apportionment has not yet been realized. Ideally, future studies will quantify detailed emission rates of microorganisms from each source and will identify the relative contribution of each source to the indoor air microbiome. This information could then be used to probe fundamental relationships between specific sources and human health, to design interventions to improve building health and human health, or even to provide evidence for forensic investigations.1-DP2-A1112243/DP/NCCDPHP CDC HHS/United StatesDP2 AI112243/AI/NIAID NIH HHS/United States2015-12-22T00:00:00Z26694197PMC468892
Investigating the cellular toxicology of silver nanoparticles using a single-cell, mitosis-focused approach
Proper cell division is a fundamental process for the development and sustainability of healthy living organisms. Defective cell division can have deleterious effects on tissue homeostasis and can represent the first step towards disease development. The overall goal of this work was to develop and validate a new, mitosis-based, single-cell toxicity approach. This contributes to the current need of toxicology research to replace animal testing with predictive in vitro models. Cell division-based assays would be better at predicting risk than other commonly used in vitro measurements, such as persistent cell cycle arrest or cell death. Finally, single-cell microscopic analysis provides far deeper insight into the underlying toxicity mechanism(s) than bulk cell population measurements. To meet our goal, we investigated the toxicity of silver nanoparticles (AgNPs) on immortalized human retinal pigmented epithelial (RPE-1) cells. AgNPs are a major nanomaterial employed in product manufacturing due to desirable antimicrobial properties, yet toxicity reports are still confounding. RPE-1 cells were cultured in the presence of low and high doses of polyvinylpyrrolidone (PVP)-coated AgNPs for a single 24-hour treatment (acute treatment), for six 24-hour treatments administered over a period of 3 weeks (moderate treatment), or for twelve 24-hour treatments administered over a period of 6 weeks (chronic treatment). Time-lapse, phase-contrast microscopy of acutely treated cells showed that 100% of cells engulfed AgNPs, which was further confirmed by electron microscopy. Moreover, we found that higher concentrations of AgNPs resulted in large numbers of acutely treated cells becoming arrested in mitosis, dying, or dividing abnormally. In contrast, untreated cells displayed normal mitotic behavior. High-resolution fluorescence microscopy performed in treated cell populations identified an increased percentage of abnormal nuclear morphologies compared to the untreated cells. Further live-cell analysis indicated that treated cells failed cytokinesis or slipped out of mitosis more often than untreated cells. Overall, our results indicate that AgNPs impair cell division, not only further confirming toxicity to human cells, but also revealing previously unreported toxicity mechanisms and highlighting the propagation of adverse phenotypes within the cell population after exposure. Furthermore, this work illustrates that cell division-based single-cell analysis could provide an alternative to animal experimentation in the future.Master of ScienceMultiple agencies, including the U.S. Environmental Protection Agency and the National Academy of Science, are urging for a radical paradigm shift from standard, whole-animal testing to alternative and novel technologies. To meet this urgent need, we aimed to develop a new, cell division-focused toxicity assay by investigating the mechanism of toxicity from silver nanoparticles (AgNPs) on human retinal pigment epithelial (RPE-1) cells. Cultured RPE-1 cells were treated with varying concentrations of AgNPs and live-cell microscopy was used to analyze the behavior of cells undergoing cell division over a 24 hour time period. Physical interaction between cells and particles was visually observed and 100% of treated cells appeared to engulf particles. We found that higher concentrations of AgNPs resulted in large numbers of cells stalling in mitosis and/or dying. In contrast, untreated cells displayed normal mitotic behavior. High-resolution fluorescence microscopy performed in chronically treated cell populations identified an increased percentage of binucleated cells. Further live-cell analysis indicated that one major cell division defect could explain the binucleated cell phenotype. Indeed, treated cells failed cytokinesis (cytoplasmic division following mitotic chromosome segregation) more often than control cells. Overall, our results indicate that AgNPs specifically impair cell division, not only further confirming toxicity to human cells, but also revealing specific, previously unreported toxicity mechanisms and highlighting the propagation of adverse phenotypes within the cell population after exposure. Furthermore, this work illustrates that cell division-based assays and ingle-cell analysis could greatly benefit chemical safety experimentation in the future
Computational Tools for Chemical Data Assimilation with CMAQ
The Community Multiscale Air Quality (CMAQ) system is the Environmental Protection Agency's main modeling tool for atmospheric pollution studies. CMAQ-ADJ, the adjoint model of CMAQ, offers new analysis capabilities such as receptor-oriented sensitivity analysis and chemical data assimilation.
This thesis presents the construction, validation, and properties of new adjoint modules in CMAQ, and illustrates their use in sensitivity analyses and data assimilation experiments. The new module of discrete adjoint of advection is implemented with the aid of automatic differentiation tool (TAMC) and is fully validated by comparing the adjoint sensitivities with finite difference values. In addition, adjoint sensitivity with respect to boundary conditions and boundary condition scaling factors are developed and validated in CMAQ.
To investigate numerically the impact of the continuous and discrete advection adjoints on data assimilation, various four dimensional variational (4D-Var) data assimilation experiments are carried out with the 1D advection PDE, and with CMAQ advection using synthetic and real observation data. The results show that optimization procedure gives better estimates of the reference initial condition and converges faster when using gradients computed by the continuous adjoint approach. This counter-intuitive result is explained using the nonlinearity properties of the piecewise parabolic method (the numerical discretization of advection in CMAQ).
Data assimilation experiments are carried out using real observation data. The simulation domain encompasses Texas and the simulation period is August 30 to September 1, 2006. Data assimilation is used to improve both initial and boundary conditions. These experiments further validate the tools developed in this thesis.Master of Scienc
Pilot Validation of VSMOKE with Implications for Smoke Management Regulations
Prescribed burning (Rx) has become increasingly subjected to various regulations. Among these regulations are ordinances that restrict downwind impacts of smoke from prescribed fires. Regulations can severely limit burn managers and private landowners from using Rx as a forest management tool. This research can help us move away from these simplistic regulations, and help promote a regulatory environment in which scientific tools and knowledge are used to prohibit only activities for which the evidence suggests there will be adverse consequences.
This research was divided into three parts that consisted of: (1) a pilot validation of the smoke emission model VSMOKE-GIS; (2) review of southeastern states' smoke management guidelines (SMG); and (3) a geographic analysis of Virginian's current SMG. VSMOKE-GIS showed good accuracy in predicting the PM2.5 concentration and location of the smoke plume downwind. Criteria were identified when managing Rx smoke and the strengths, weaknesses, and implications were discussed of the Rx programs. The geographic analysis demonstrated quantitatively how much area may be impacted with minimal apparent benefit. This research should provide a clearer spatial picture of the smoke management barriers associated with Rx on private woodlands in Virginia. These results should be a useful tool in developing a regulatory environment that encourages Rx when the conditions are optimal. We conclude with future recommendations for Virginia.Master of Scienc
Virus Transmission in Respiratory Aerosol: The Roles of Trace Gas Uptake, Ion Diffusivity, Viscosity, and pH
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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