Evaluating and Understanding Parameterized Convective Processes and their Role in the Development of Mesoscale Precipitation Systems

Research efforts during the second year have centered on improving the manner in which convective stabilization is achieved in the Penn State/NCAR mesoscale model MM5. Ways of improving this stabilization have been investigated by (1) refining the partitioning between the Kain-Fritsch convective parameterization scheme and the grid scale by introducing a form of moist convective adjustment; (2) using radar data to define locations of subgrid-scale convection during a dynamic initialization period; and (3) parameterizing deep-convective feedbacks as subgrid-scale sources and sinks of mass. These investigations were conducted by simulating a long-lived convectively-generated mesoscale vortex that occurred during 14-18 Jul. 1982 and the 10-11 Jun. 1985 squall line that occurred over the Kansas-Oklahoma region during the PRE-STORM experiment. The long-lived vortex tracked across the central Plains states and was responsible for multiple convective outbreaks during its lifetime

Altered high-energy phosphate and membrane metabolism in Pelizaeus-Merzbacher disease using phosphorus magnetic resonance spectroscopy

Pelizaeus-Merzbacher disease is an X-linked recessive leucodystrophy of the central nervous system caused by mutations affecting the major myelin protein, proteolipid protein 1. The extent of the altered in vivo neurochemistry of protein, proteolipid protein 1 duplications, the most common form of Pelizaeus-Merzbacher disease, is, however, poorly understood. Phosphorus magnetic resonance spectroscopy is the only in vivo technique that can assess the biochemistry associated with high-energy phosphate and membrane phospholipid metabolism across different cortical, subcortical and white matter areas. In this cross-sectional study, whole-brain, multi-voxel phosphorus magnetic resonance spectroscopy was acquired at 3 T on 14 patients with Pelizaeus-Merzbacher disease with protein, proteolipid protein 1 duplications and 23 healthy controls (all males). Anabolic and catabolic levels of membrane phospholipids (phosphocholine and phosphoethanolamine, and glycerophosphoethanolamine and glycerophosphocholine, respectively), as well as phosphocreatine, inorganic orthophosphate and adenosine triphosphate levels relative to the total phosphorus magnetic resonance spectroscopy signal from 12 different cortical and subcortical areas were compared between the two groups. Independent of brain area, phosphocholine, glycerophosphoethanolamine and inorganic orthophosphate levels were significantly lower (P = 0.0025, P \u3c 0.0001 and P = 0.0002) and phosphocreatine levels were significantly higher (P \u3c 0.0001) in Pelizaeus-Merzbacher disease patients compared with controls. Additionally, there was a significant group-by-brain area interaction for phosphocreatine with post-hoc analyses demonstrating significantly higher phosphocreatine levels in patients with Pelizaeus-Merzbacher disease compared with controls across multiple brain areas (anterior and posterior white matter, superior parietal lobe, posterior cingulate cortex, hippocampus, occipital cortex, striatum and thalamus; all P ≤ 0.0042). Phosphoethanolamine, glycerophosphoethanolamine and adenosine triphosphate levels were not significantly different between groups. For the first-time, widespread alterations in phosphorus magnetic resonance spectroscopy metabolite levels of Pelizaeus-Merzbacher disease patients are being reported. Specifically, increased high-energy phosphate storage levels of phosphocreatine concomitant with decreased inorganic orthophosphate across multiple areas suggest a widespread reduction in the high-energy phosphate utilization in Pelizaeus-Merzbacher disease, and the membrane phospholipid metabolite deficits suggest a widespread degradation in the neuropil content/maintenance of patients with Pelizaeus-Merzbacher disease which includes axons, dendrites and astrocytes within cortex and the myelin microstructure and oligodendrocytes within white matter. These results provide greater insight into the neuropathology of Pelizaeus-Merzbacher disease both in terms of energy expenditure and membrane phospholipid metabolites. Future longitudinal studies are warranted to investigate the utility of phosphorus magnetic resonance spectroscopy as surrogate biomarkers in monitoring treatment intervention for Pelizaeus-Merzbacher disease

Plasmodium Secretion Induces Hepatocyte Lysosome Exocytosis and Promotes Parasite Entry.

The invasion of a suitable host hepatocyte by Plasmodium sporozoites is an essential step in malaria infection. We demonstrate that in infected hepatocytes, lysosomes are redistributed away from the nucleus, and surface exposure of lysosome-associated membrane protein 1 (LAMP1) is increased. Lysosome exocytosis in infected cells occurs independently of sporozoite traversal. Instead, a sporozoite-secreted factor is sufficient for the process. Knockdown of SNARE proteins involved in lysosome-plasma membrane fusion reduces lysosome exocytosis and Plasmodium infection. In contrast, promoting fusion between the lysosome and plasma membrane dramatically increases infection. Our work demonstrates parallels between Plasmodium sporozoite entry of hepatocytes and infection by the excavate pathogen Trypanosoma cruzi and raises the question of whether convergent evolution has shaped host cell invasion by divergent pathogens

Validation and Accuracy of Synovial Alpha Defensin in a Suburban Academic Center after Implantation as Part of the Workup for Periprosthetic Joint infections

Introduction Periprosthetic joint infection (PJI) is a leading cause of total hip and knee arthroplasty failure. The Musculoskeletal Infection Society (MSIS) criteria for PJI has allowed diagnosis standardization. To increase the MSIS criteria accuracy, synovial fluid biomarkers have been tested. Studies evaluating synovial alpha defensin have reported both sensitivity and specificity up to 100%. In this study, we report our analysis on the use of alpha defensin testing in a suburban academic tertiary referral center. Methods We performed a retrospective analysis of a prospectively collected database of 133 patients tested for PJI over a 6 year period. From 2014, our standard infection evaluation protocol included synovial alpha defensin fluid analysis. Complete testing data was available on 128 patients. Both primary and revision total hip and knee arthroplasty were included. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using the 2011 MSIS criteria. T-tests were performed for parametric data. Results Synovial testing of alpha defensin for PJI had a 95.00% sensitivity, a 91.67% specificity, a 67.86% PPV and a 99.00% NPV. Positive alpha defensin tests were corelated with positive serum and synovial CRP, synovial WBC count, and synovial polymorphonuclear cell percent. There was no correlation between positive synovial alpha defensin and age, sex, smoking or diabetic status. Conclusion Synovial testing for alpha defensin in an unbiased cohort gives high sensitivity and NPV comparable to published literature. We recommend using synovial alpha defensin testing for suspected PJI cases, as an additional data point to help determine likelihood

Ions for LHC: Towards Completion of the Injector Chain

The commissioning of CERN's ion injector complex [1] to allow 1.1 PeV collisions of ions in LHC is well under way. After the Low Energy Ion Ring (LEIR) in 2005 [2] and the Proton Synchrotron (PS) in 2006 [3], the Super Proton Synchrotron (SPS) has now been commissioned with the 'Early' ion beam, which should give a luminosity of $5×10^{25}cm^{-2}s^{-1}$ in the LHC. This paper summarizes the operation in 2007 of all the machines involved in the ion injection chain

The DYMECS project: a statistical approach for the evaluation of convective storms in high-resolution NWP models

A new frontier in weather forecasting is emerging by operational forecast models now being run at convection-permitting resolutions at many national weather services. However, this is not a panacea; significant systematic errors remain in the character of convective storms and rainfall distributions. The DYMECS project (Dynamical and Microphysical Evolution of Convective Storms) is taking a fundamentally new approach to evaluate and improve such models: rather than relying on a limited number of cases, which may not be representative, we have gathered a large database of 3D storm structures on 40 convective days using the Chilbolton radar in southern England. We have related these structures to storm life-cycles derived by tracking features in the rainfall from the UK radar network, and compared them statistically to storm structures in the Met Office model, which we ran at horizontal grid length between 1.5 km and 100 m, including simulations with different subgrid mixing length. We also evaluated the scale and intensity of convective updrafts using a new radar technique. We find that the horizontal size of simulated convective storms and the updrafts within them is much too large at 1.5-km resolution, such that the convective mass flux of individual updrafts can be too large by an order of magnitude. The scale of precipitation cores and updrafts decreases steadily with decreasing grid lengths, as does the typical storm lifetime. The 200-m grid-length simulation with standard mixing length performs best over all diagnostics, although a greater mixing length improves the representation of deep convective storms