Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis.

In pneumococcal meningitis, bacterial growth in the cerebrospinal fluid results in lysis, the release of toxic factors, and subsequent neuroinflammation. Exposure of primary murine glia to Streptococcus pneumoniae lysates leads to strong proinflammatory cytokine and chemokine production, blocked by inhibition of the intracellular innate receptor Nod1. Lysates enhance dynamin-dependent endocytosis, and dynamin inhibition reduces neuroinflammation, blocking ligand internalization. Here we identify the cholesterol-dependent cytolysin pneumolysin as a pro-endocytotic factor in lysates, its elimination reduces their proinflammatory effect. Only pore-competent pneumolysin enhances endocytosis in a dynamin-, phosphatidylinositol-3-kinase- and potassium-dependent manner. Endocytic enhancement is limited to toxin-exposed parts of the membrane, the effect is rapid and pneumolysin permanently alters membrane dynamics. In a murine model of pneumococcal meningitis, mice treated with chlorpromazine, a neuroleptic with a complementary endocytosis inhibitory effect show reduced neuroinflammation. Thus, the dynamin-dependent endocytosis emerges as a factor in pneumococcal neuroinflammation, and its enhancement by a cytolysin represents a proinflammatory control mechanism

Factors that influence response classifications in chemotherapy treated patient-derived xenografts (PDX).

In this study, we investigated the impact of initial tumor volume, rate of tumor growth, cohort size, study duration, and data analysis method on chemotherapy treatment response classifications in patient-derived xenografts (PDXs). The analyses were conducted on cisplatin treatment response data for 70 PDX models representing ten cancer types with up to 28-day study duration and cohort sizes of 3-10 tumor-bearing mice. The results demonstrated that a 21-day dosing study using a cohort size of eight was necessary to reliably detect responsive models (i.e., tumor volume ratio of treated animals to control between 0.1 and 0.42)-independent of analysis method. A cohort of three tumor-bearing animals led to a reliable classification of models that were both highly responsive and highly nonresponsive to cisplatin (i.e., tumor volume ratio of treated animals to control animals less than 0.10). In our set of PDXs, we found that tumor growth rate in the control group impacted treatment response classification more than initial tumor volume. We repeated the study design factors using docetaxel treated PDXs with consistent results. Our results highlight the importance of defining endpoints for PDX dosing studies when deciding the size of cohorts to use in dosing studies and illustrate that response classifications for a study do not differ significantly across the commonly used analysis methods that are based on tumor volume changes in treatment versus control groups

International Space Station (ISS) Anomalies Trending Study

The NASA Engineering and Safety Center (NESC) set out to utilize data mining and trending techniques to review the anomaly history of the International Space Station (ISS) and provide tools for discipline experts not involved with the ISS Program to search anomaly data to aid in identification of areas that may warrant further investigation. Additionally, the assessment team aimed to develop an approach and skillset for integrating data sets, with the intent of providing an enriched data set for discipline experts to investigate that is easier to navigate, particularly in light of ISS aging and the plan to extend its life into the late 2020s. This document contains the Appendices to the Volume I report

Surface oxidation of liquid Sn

We report the results of an x-ray scattering study that reveals oxidation kinetics and formation of a previously unreported crystalline phase of SnO at the liquid-vapour interface of Sn. Our experiments reveal that the pure liquid Sn surface does not react with molecular oxygen below an activation pressure of \~5.0*10-6 Torr. Above that pressure a rough solid Sn oxide grows over the liquid metal surface. Once the activation pressure has been exceeded the oxidation proceeds at pressures below the oxidation pressure threshold. The observed diffraction pattern associated with the surface oxidation does not match any of the known Sn oxide phases. The data have an explicit signature of the face-centred cubic structure, however it requires lattice parameters that are about 9% smaller than those reported for cubic structures of high-pressure phases of Sn oxides. Keywords: X-ray scattering, diffraction, and reflection; Oxidation; Surface chemical reaction; Surface structure, morphology, roughness, and topography; Tin; Tin oxides; Liquid surfaces; Polycrystalline thin filmsComment: 18 pages, 6 figures, 1 table; Submitted to Surface Scienc

International Space Station (ISS) Anomalies Trending Study

The NASA Engineering and Safety Center (NESC) set out to utilize data mining and trending techniques to review the anomaly history of the International Space Station (ISS) and provide tools for discipline experts not involved with the ISS Program to search anomaly data to aid in identification of areas that may warrant further investigation. Additionally, the assessment team aimed to develop an approach and skillset for integrating data sets, with the intent of providing an enriched data set for discipline experts to investigate that is easier to navigate, particularly in light of ISS aging and the plan to extend its life into the late 2020s. This report contains the outcome of the NESC Assessment

Winter-to-summer transition of Arctic sea ice breakup and floe size distribution in the Beaufort Sea

Breakup of the near-continuous winter sea ice into discrete summer ice floes is an important transition that dictates the evolution and fate of the marginal ice zone (MIZ) of the Arctic Ocean. During the winter of 2014, more than 50 autonomous drifting buoys were deployed in four separate clusters on the sea ice in the Beaufort Sea, as part of the Office of Naval Research MIZ program. These systems measured the ocean-ice-atmosphere properties at their location whilst the sea ice parameters in the surrounding area of these buoy clusters were continuously monitored by satellite TerraSAR-X Synthetic Aperture Radar. This approach provided a unique Lagrangian view of the winter-to-summer transition of sea ice breakup and floe size distribution at each cluster between March and August. The results show the critical timings of a) temporary breakup of winter sea ice coinciding with strong wind events and b) spring breakup (during surface melt, melt ponding and drainage) leading to distinctive summer ice floes. Importantly our results suggest that summer sea ice floe distribution is potentially affected by the state of winter sea ice, including the composition and fracturing (caused by deformation events) of winter sea ice, and that substantial mid-summer breakup of sea ice floes is likely linked to the timing of thermodynamic melt of sea ice in the area. As the rate of deformation and thermodynamic melt of sea ice has been increasing in the MIZ in the Beaufort Sea, our results suggest that these elevated factors would promote faster and more enhanced breakup of sea ice, leading to a higher melt rate of sea ice and thus a more rapid advance of the summer MIZ

Factors that influence response classifications in chemotherapy treated patient-derived xenografts (PDX)

In this study, we investigated the impact of initial tumor volume, rate of tumor growth, cohort size, study duration, and data analysis method on chemotherapy treatment response classifications in patient-derived xenografts (PDXs). The analyses were conducted on cisplatin treatment response data for 70 PDX models representing ten cancer types with up to 28-day study duration and cohort sizes of 3–10 tumor-bearing mice. The results demonstrated that a 21-day dosing study using a cohort size of eight was necessary to reliably detect responsive models (i.e., tumor volume ratio of treated animals to control between 0.1 and 0.42)—independent of analysis method. A cohort of three tumor-bearing animals led to a reliable classification of models that were both highly responsive and highly nonresponsive to cisplatin (i.e., tumor volume ratio of treated animals to control animals less than 0.10). In our set of PDXs, we found that tumor growth rate in the control group impacted treatment response classification more than initial tumor volume. We repeated the study design factors using docetaxel treated PDXs with consistent results. Our results highlight the importance of defining endpoints for PDX dosing studies when deciding the size of cohorts to use in dosing studies and illustrate that response classifications for a study do not differ significantly across the commonly used analysis methods that are based on tumor volume changes in treatment versus control groups

Displacement Measurement Errors from Moving Platforms

Errors in eddy correlation measurements from moving platforms (aircraft, ships, buoys, blimps, tethered balloons, and kites) include contamination of the measured fluctuations by superficial fluctuations associated with vertical movement of the platform in the presence of mean vertical gradients. Such errors occur even with perfect removal of the motion of the platform. These errors are investigated here from eddy correlation data collected from the LongEZ research aircraft and the air–sea interaction spar (ASIS) buoy during the Shoaling Waves Experiment (SHOWEX)

Significant internal waves and internal tides measured northeast of Taiwan

Author Posting. © The Author(s), 2013. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 71 (2013): 47-81, doi:10.1357/002224013807343416.Internal gravity waves in an area northeast of Taiwan are characterized using data from multiple sensor types. The data set includes intermittent information collected from a ship and short time series from moorings. Modeled nonlinear waves are fitted to observed nonlinear waves to provide self-consistent estimates of multiple wave parameters. A nonlinear internal wave of over 50 m amplitude, observed in deep water, is examined in detail. This wave was moving northward from the southern Okinawa Trough toward the continental shelf, and presumably formed from internal tides propagating northward from the Ilan Ridge area. A possible scenario for the formation of this wave from the internal tide is compared to related behavior south of Taiwan. On the outer continental shelf, a few large internal waves with maximum displacement greater than one-quarter of the water depth were measured with moorings. Sensors aboard ship and satellite recorded waves in this area traveling in many directions. Two possible causes (not mutually exclusive) for the multiple wave directions are scattering of nonlinear internal waves arriving from the south, and variable local generation of nonlinear gravity waves by the strong tidal and internal tidal currents. Internal tides on the shelf are relatively strong, among the strongest measured, having about 10 times greater kinetic energy density than numerous low-energy sites, which is consistent with the strong barotropic tides of the area. The ratio of diurnal baroclinic to barotropic kinetic energy found in this area is unusually high.Funding for the use of RV OR1 was provided by the National Science Council of Taiwan. TFD was supported by the Office of Naval Research (ONR) Ocean Acoustics Program under grants N00014-05-1-0482 and N00014-11-1-0194. AEN was supported under ONR grant N00014- 08-1-0763, and GG under ONR grant N00014-07-01-0482. HCG and MJC were supported by ONR grants N00014-09-1-0392 and N00014-07-1-0650