VX Hydrolysis by Human Serum Paraoxonase 1: A Comparison of Experimental and Computational Results

Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VXts) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VXts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VXts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.United States. Defense Threat Reduction Agenc

Monitoring settling and consolidation of fluid mud in a laboratory using ultrasonic measurements

Ultrasound measurements are routinely used to evaluate the safe depth for ships navigation - nautical depth - at waterways and ports using single-beam dual-frequency echo-sounders. The nautical depth is routinely defined by suspension density in the range of 1100–1300 kg/m3 in the mud layer. While ultrasound measurements have a weak sensitivity to density variations, calibration is always needed to convert ultrasound measurements into reliable indicators for nautical depth levels in the mud layers using densely distributed density rheological in-situ measurements. We present a laboratory ultrasonic transmission experiment to monitor the fluid mud’s settling and consolidation processes using a sample from the Port of Rotterdam. We use P- and S-wave ultrasonic transducers in the frequency range between 200 to 1000 kHz. Our results show that the P-wave velocities slightly increase during the consolidation and settling process while the P-wave amplitudes decrease. On the other hand, we observe a high S-wave velocity that increases together with amplitudes over time. The P- and S-wave amplitude and S-wave velocity variation over time correlate well with the mud average density variation. The presented results can be very useful for fluid-mud monitoring at a lab scale, besides possible utilization for large-scale monitoring field campaigns

ON THE INCIDENCE OF THE DIFFERENT FORMS OF PRIMARY GLAUCOMA

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Generation of unusually low frequency plasmaspheric hiss

It has been reported from Van Allen Probe observations that plasmaspheric hiss intensification in the outer plasmasphere, associated with a substorm injection on 30 September 2012, occurred with a peak frequency near 100 Hz, well below the typical plasmaspheric hiss frequency range, extending down to ∼20 Hz. We examine this event of unusually low frequency plasmaspheric hiss to understand its generation mechanism. Quantitative analysis is performed by simulating wave raypaths via the HOTRAY ray tracing code with measured plasma density and calculating raypath-integrated wave gain evaluated using the measured energetic electron distribution. We demonstrate that the growth rate due to substorm-injected electrons is positive but rather weak, leading to small wave gain (∼10 dB) during a single equatorial crossing. Propagation characteristics aided by the sharp density gradient associated with the plasmapause, however, can enable these low-frequency waves to undergo cyclic raypaths, which return to the unstable region leading to repeated amplification to yield sufficient net wave gain (>40 dB) to allow waves to grow from the thermal noise

Illumination diagnosis for retrieval of reflections from ambient-noise seismic data in the Siilinjärvi mining site, Finland

Reflection seismic methods are becoming popular in mineral exploration, because they allow high-resolution delineation of the exploration targets, even at great depths. Seismic interferometry can be used to retrieve reflections from passive seismic data, removing the need for active seismic sources and, therefore, reducing the cost and environmental impact of exploration. The retrieval of reflections can be challenging, since passive seismic records are typically dominated by surface waves. Therefore, illumination diagnosis, a method which allows the isolation of the portions of the passive data where body-wave signals are stronger, can be a valuable step that improves the quality of the reflections retrieved from seismic interferometry and reduces the overall computational cost of the processing stage. Here, we validate the performance of the method to effectively isolate the portions of the passive data dominated by body waves and apply it on an ambient-noise seismic dataset acquired in the Siilinjärvi mining site in Finland