Scientific Opportunities for Monitoring of Environmental Remediation Sites (SOMERS) - 12224

ABSTRACT The US Department of Energy (DOE) is responsible for risk reduction and cleanup of its nuclear weapons complex. DOE maintains the largest cleanup program in the world, currently spanning over a million acres in 13 states. The inventory of contaminated materials includes 90 million gallons of radioactive waste, 6.4 trillion liters of groundwater, and 40 million cubic meters of soil and debris. It is not feasible to completely restore many sites to predisposal conditions. Any contamination left in place will require monitoring, engineering controls and/or land use restrictions to protect human health and environment. Research and development efforts to date have focused on improving characterization and remediation. Yet, monitoring will result in the largest life-cycle costs and will be critical to improving performance and protection. Through an inter-disciplinary effort, DOE is addressing a need to advance monitoring approaches from sole reliance on cost-and labor-intensive point-source monitoring to integrated systems-based approaches such as flux-based approaches and the use of early indicator parameters. Key objectives include identifying current scientific, technical and implementation opportunities and challenges, prioritizing science and technology strategies to meet current needs within the DOE complex for the most challenging environments, and developing an integrated and risk-informed monitoring framework

Scientific Opportunities for Monitoring at Environmental Remediation Sites (SOMERS): Integrated Systems-Based Approaches to Monitoring

Through an inter-disciplinary effort, DOE is addressing a need to advance monitoring approaches from sole reliance on cost- and labor-intensive point-source monitoring to integrated systems-based approaches such as flux-based approaches and the use of early indicator parameters. Key objectives include identifying current scientific, technical and implementation opportunities and challenges, prioritizing science and technology strategies to meet current needs within the DOE complex for the most challenging environments, and developing an integrated and risk-informed monitoring framework

Analyzing and Modeling Real-World Phenomena with Complex Networks: A Survey of Applications

The success of new scientific areas can be assessed by their potential for contributing to new theoretical approaches and in applications to real-world problems. Complex networks have fared extremely well in both of these aspects, with their sound theoretical basis developed over the years and with a variety of applications. In this survey, we analyze the applications of complex networks to real-world problems and data, with emphasis in representation, analysis and modeling, after an introduction to the main concepts and models. A diversity of phenomena are surveyed, which may be classified into no less than 22 areas, providing a clear indication of the impact of the field of complex networks.Comment: 103 pages, 3 figures and 7 tables. A working manuscript, suggestions are welcome

Relation of regional tidal lung expansion with inflammatory activation in early ventilator-induced lung injury: a pet imaging approach

Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.Mechanical ventilation is a life-saving intervention in patients with respiratory failure, but can exacerbate lung injury or produce inflammation in healthy lungs, side effects termed ventilator-induced lung injury (VILI). One putative mechanism of VILI is the triggering of inflammation through cyclic stretching of tissue. Studies in small animals have shown that high tidal volume ventilation results in cytokine production, macrophage activation, and neutrophil infiltration in the lungs. Exposure to lipopolysaccharide (LPS) may amplify these effects. However, translation of those findings to heterogeneously expanding large-animal lungs has been limited. We hypothesized that in heterogeneous lungs comparable in size to humans, regional inflammatory activation is directly related to both the magnitude and heterogeneity of tidal expansion, and that LPS exposure increases the inflammatory response to those mechanical factors. The goal of this study was to develop quantitative positron emission tomography (PET) imaging techniques to test these hypotheses in a large animal model of VILI and LPS-induced lung injury. First, we developed a novel approach to measure regional tidal lung expansion using respiratory-gated PET of inhaled 13N-nitrogen (13NN). Estimates of local expansion were validated against regional specific ventilation measured from 13NN washout rates in mechanically ventilated sheep. Second, we advanced PET techniques for quantification of ventilation heterogeneity underlying the PET resolution, and implemented a new length-scale analysis for ventilation heterogeneity. Finally, we combined these 13NN-PET techniques with dynamic 18F-FDG-PET imaging to study the relationships between regional tidal expansion, ventilation heterogeneity, and inflammatory activation in sheep mechanically ventilated with and without intravenous LPS infusion. We found that local inflammatory activation was linearly related to regional tidal expansion in initially normal lungs. Sensitivity to tidal expansion was enhanced with LPS exposure, indicating local synergy between expansion and LPS. Ventilation heterogeneity affected inflammatory activation only in LPS-exposed lungs. Protective ventilation reduced peak local inflammation by homogenizing and decreasing regional tidal expansion. These findings indicate that mechanical ventilation characterized by heterogeneous regional expansion places the lung at risk for focal inflammation, particularly in the presence of LPS. Thus, preventing local amplification of expansion through the use of ventilation strategies promoting homogeneous expansion may help to attenuate VILI

Design of a Novel Equi-Biaxial Stretcher for Live Cellular and Subcellular Imaging.

Cells in the body experience various mechanical stimuli that are often essential to proper cell function. In order to study the effects of mechanical stretch on cell function, several devices have been built to deliver cyclic stretch to cells; however, they are generally not practical for live cell imaging. We introduce a novel device that allows for live cell imaging, using either an upright or inverted microscope, during the delivery of cyclic stretch, which can vary in amplitude and frequency. The device delivers equi-biaxial strain to cells seeded on an elastic membrane via indentation of the membrane. Membrane area strain was calibrated to indenter depth and the device showed repeatable and accurate delivery of strain at the scale of individual cells. At the whole cell level, changes in intracellular calcium were measured at different membrane area strains, and showed an amplitude-dependent response. At the subcellular level, the mitochondrial network was imaged at increasing membrane area strains to demonstrate that stretch can lead to mitochondrial fission in lung fibroblasts. The device is a useful tool for studying transient as well as long-term mechanotransduction as it allows for simultaneous stretching and imaging of live cells in the presence of various chemical stimuli

Design of a Novel Equi-Biaxial Stretcher for Live Cellular and Subcellular Imaging - Fig 2

<p>(<i>A</i>) Nonlinear relationship between the indenter depth and the corresponding change in surface area of a demarcated region on the membrane; this calibration curve was subsequently used to prescribe strain waveforms as a function of indenter depth. Data points represent the average of n = 3 calibrations with different membranes; standard deviation bars (not shown) are smaller than symbols. (<i>B</i>) Representative sinusoidal waveform applied to membrane (amplitude, 20% strain; frequency, 0.0464 Hz), the input waveform (solid line) and the observed change in surface area (open circles) are shown demonstrating close agreement between input and measurement. (<i>C</i>) Frequency response of the device is flat for stretch frequencies between 0.01–1.0 Hz; sinusoidal waveforms with prescribed strain amplitudes of 20% (filled triangles) and 40% (open squares) are shown with reference lines, error bars represent the standard deviations (N = 3). (<i>D</i>) <i>Left</i>: characteristic image of marker beads used to track micro strain; <i>Right</i>: detection algorithm showing beads at baseline (green) and after applied strain (magenta), specific beads are tracked and the areas enclosed by their polygons are used to determine the corresponding micro strain. (<i>E</i>) Change in micro strain closely follows the prescribed macrostrain, line of identity is shown for reference; error bars represent standard deviations (n = 9).</p

Intracellular calcium level responses of primary bovine fibroblasts to single sinusoidal equi-biaxial strains.

<p>Cells were loaded with Fluo4 calcium indicator dye and subjected to strains of 3 or 10% change in membrane surface area (ΔSA). (A) Following single 6 s long stretch (dotted line), cells stretched to 10% ΔSA showed large transient increases in fluorescence relative to baseline (mean of 77 cells), while cells stretched to 3% ΔSA showed little response (mean of 44 cells). Images of cells stretched to 10% ΔSA revealed differences between neighboring cells in the timing of their response to stretch, with some cells responding immediately and other requiring up to 10 s to respond. (B) The changes in fluorescence were significantly greater with 10% ΔSA than with 3% ΔSA (p<0.001).</p

Response of intracellular calcium levels in bovine fibroblasts up to one hour of continuous sinusoidal stretching with maximum amplitude of 10% change in membrane surface area.

<p>Average ratios of Fura2 fluorescence at 340 and 380 nm excitation wavelengths were computed in each of 11 cells. Individual cell responses varied (A), but there was an overall trend of increasing Fura2 ratios over time, with significant increases present at 20 and 60 min relative to baseline (B). **, p<0.01; ***, p<0.001</p

Regional pulmonary perfusion, blood volume, and their relationship change in experimental early ARDS

Abstract Regional pulmonary perfusion (Q) has been investigated using blood volume (Fb) imaging as an easier-to-measure surrogate. However, it is unclear if changing pulmonary conditions could affect their relationship. We hypothesized that vascular changes in early acute respiratory distress syndrome (ARDS) affect Q and Fb differently. Five sheep were anesthetized and received lung protective mechanical ventilation for 20 h while endotoxin was continuously infused. Using dynamic 18F-FDG and 13NN Positron Emission Tomography (PET), regional Fb and Q were analysed in 30 regions of interest (ROIs) and normalized by tissue content (Fbn and Qn, respectively). After 20 h, the lung injury showed characteristics of early ARDS, including gas exchange and lung mechanics. PET images of Fbn and Qn showed substantial differences between baseline and lung injury. Lung injury caused a significant change in the Fbn-Qn relationship compared to baseline (p < 0.001). The best models at baseline and lung injury were Fbn = 0.32 + 0.690Qn and Fbn = 1.684Qn–0.538Qn 2, respectively. Endotoxine-associated early ARDS changed the relationship between Fb and Q, shifting from linear to curvilinear. Effects of endotoxin exposure on the vasoactive blood flow regulation were most likely the key factor for this change limiting the quantitative accuracy of Fb imaging as a surrogate for regional Q