Indicators of replicative damage in equine tendon fibroblast monolayers

<p>Background: Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it.</p> <p>Results: We found significant evidence of replicative stress, initially observing consistently large numbers of binucleate (BN) cells. A more variable but prominent feature was the presence of numerous gammaH2AX (γH2AX) puncta in nuclei, this being a histone protein that is phosphorylated in response to DNA double-stranded breaks (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53 (ser15) and p21) occurred most frequently in BN cells; however, their numbers did not correlate with DNA damage levels and it is likely that the two processes have different causative mechanisms. Such remarkable levels of injury and binucleation are usually associated with irradiation, or treatment with cytoskeletal-disrupting agents.</p> <p>Both DSBs and BN cells were greatest in subconfluent (replicating) monolayers. The DNA-damaged cells co-expressed the replication markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of culture establishment, fibroblasts continued to express DNA breaks with each replicative cycle. However, significant levels of cell death were not measured, suggesting that DNA repair was occurring. Comet assays showed that DNA repair was delayed in proportion to levels of genotoxic stress.</p> <p>Conclusions: Researchers using tendon fibroblast monolayers should assess their “health” using γH2AX labelling. Continued use of early passage cultures expressing initially high levels of γH2AX puncta should be avoided for mechanistic studies and ex-vivo therapeutic applications, as this will not be resolved with further replicative cycling. Low density cell culture should be avoided as it enriches for both DNA damage and mitotic defects (polyploidy). As monolayers differing only slightly in baseline DNA damage levels showed markedly variable responses to a further injury, studies of effects of various stressors on tendon cells must be very carefully controlled.</p&gt

Nuclear Analysis for Near Term Fusion Devices

A Next Step Options (NSO) study was initiated to consider the logical steps that might be undertaken to restructure the U.S. Fusion Sciences Program. Most of the effort was concentrated on designing the Fusion Ignition Research Experiment (FIRE), which is in the preconceptual design phase. It utilizes 16 cryogenically cooled wedged copper TF coils with beryllium copper in the inner legs and OFHC copper in the outer legs. We provided significant contributions in the areas of neutronics, shielding and activation analyses. The design went through different changes. Early in the year 2002 the baseline design changed from a major radius of 2 m to a major radius of 2.14 m and an aspect ratio of 3.6. In addition the fusion power during the DT pulses changed from 200 MW to 150 MW. We spent significant part of the effort calculating the nuclear performance parameters for the final baseline design. While pulses producing a total of 5 TJ of DT fusion energy and 0.5 TJ of DD fusion energy were considered in the previous designs, a detailed experimental plan was developed that results in higher total fusion energy. We assessed the impact on the peak magnet insulator dose. Multi-dimensional calculations were performed also to determine the impact of plasma shape and profile on he peak radiation effects in the TF coils. We performed multi-dimensional calculations for one of the most critical diagnostics ports to assess streaming and determine the nuclear environment at the sensitive components. The radwaste level and volume was quantified for the different components of FIRE

Inelastic Proton Scattering to Unnatural Parity States in Even Mass Nuclei

This work was supported by National Science Foundation Grant PHY 76-84033 and Indiana Universit

Studies of Knock-Out Reactions

This work was supported by National Science Foundation Grant PHY 75-00289 and Indiana Universit

Inelastic Proton Scattering from 12-C, 16-O, 6-Li

This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

Studies of Knock-Out Reactions

This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

Studies of Knock-Out Reactions

This work was supported by National Science Foundation Grant PHY 76-84033 and Indiana Universit

Perceived Noise Analysis for Offset Jets Applied to Commercial Supersonic Aircraft

A systems analysis was performed with experimental jet noise data, engine/aircraft performance codes and aircraft noise prediction codes to assess takeoff noise levels and mission range for conceptual supersonic commercial aircraft. A parametric study was done to identify viable engine cycles that meet NASA's N+2 goals for noise and performance. Model scale data from offset jets were used as input to the aircraft noise prediction code to determine the expected sound levels for the lateral certification point where jet noise dominates over all other noise sources. The noise predictions were used to determine the optimal orientation of the offset nozzles to minimize the noise at the lateral microphone location. An alternative takeoff procedure called "programmed lapse rate" was evaluated for noise reduction benefits. Results show there are two types of engines that provide acceptable mission range performance; one is a conventional mixed-flow turbofan and the other is a three-stream variable-cycle engine. Separate flow offset nozzles reduce the noise directed toward the thicker side of the outer flow stream, but have less benefit as the core nozzle pressure ratio is reduced. At the systems level for a three-engine N+2 aircraft with full throttle takeoff, there is a 1.4 EPNdB margin to Chapter 3 noise regulations predicted for the lateral certification point (assuming jet noise dominates). With a 10% reduction in thrust just after clearing the runway, the margin increases to 5.5 EPNdB. Margins to Chapter 4 and Chapter 14 levels will depend on the cumulative split between the three certification points, but it appears that low specific thrust engines with a 10% reduction in thrust (programmed lapse rate) can come close to meeting Chapter 14 noise levels. Further noise reduction is possible with engine oversizing and derated takeoff, but more detailed mission studies are needed to investigate the range impacts as well as the practical limits for safety and takeoff regulations

Active Amplification of the Terrestrial Albedo to Mitigate Climate Change: An Exploratory Study

This study explores the potential to enhance the reflectance of solar insolation by the human settlement and grassland components of the Earth's terrestrial surface as a climate change mitigation measure. Preliminary estimates derived using a static radiative transfer model indicate that such efforts could amplify the planetary albedo enough to offset the current global annual average level of radiative forcing caused by anthropogenic greenhouse gases by as much as 30 percent or 0.76 W/m2. Terrestrial albedo amplification may thus extend, by about 25 years, the time available to advance the development and use of low-emission energy conversion technologies which ultimately remain essential to mitigate long-term climate change. However, additional study is needed to confirm the estimates reported here and to assess the economic and environmental impacts of active land-surface albedo amplification as a climate change mitigation measure.Comment: 21 pages, 3 figures. In press with Mitigation and Adaptation Strategies for Global Change, Springer, N

Collision statistics of driven granular materials

We present an experimental investigation of the statistical properties of spherical granular particles on an inclined plane that are excited by an oscillating side-wall. The data is obtained by high-speed imaging and particle tracking techniques. We identify all particles in the system and link their positions to form trajectories over long times. Thus, we identify particle collisions to measure the effective coefficient of restitution and find a broad distribution of values for the same impact angles. We find that the energy inelasticity can take on values greater than one, which implies that the rotational degrees play an important role in energy transfer. We also measure the distance and the time between collision events in order to directly determine the distribution of path lengths and the free times. These distributions are shown to deviate from expected theoretical forms for elastic spheres, demonstrating the inherent clustering in this system. We describe the data with a two-parameter fitting function and use it to calculated the mean free path and collision time. We find that the ratio of these values is consistent with the average velocity. The velocity distribution are observed to be strongly non-Gaussian and do not demonstrate any apparent universal behavior. We report the scaling of the second moment, which corresponds to the granular temperature, and higher order moments as a function of distance from the driving wall. Additionally, we measure long time correlation functions in both space and in the velocities to probe diffusion in a dissipative gas.Comment: 12 pages, 4 figures, uses revtex