A Comparison of Two Shallow Water Models with Non-Conforming Adaptive Grids: classical tests

In an effort to study the applicability of adaptive mesh refinement (AMR) techniques to atmospheric models an interpolation-based spectral element shallow water model on a cubed-sphere grid is compared to a block-structured finite volume method in latitude-longitude geometry. Both models utilize a non-conforming adaptation approach which doubles the resolution at fine-coarse mesh interfaces. The underlying AMR libraries are quad-tree based and ensure that neighboring regions can only differ by one refinement level. The models are compared via selected test cases from a standard test suite for the shallow water equations. They include the advection of a cosine bell, a steady-state geostrophic flow, a flow over an idealized mountain and a Rossby-Haurwitz wave. Both static and dynamics adaptations are evaluated which reveal the strengths and weaknesses of the AMR techniques. Overall, the AMR simulations show that both models successfully place static and dynamic adaptations in local regions without requiring a fine grid in the global domain. The adaptive grids reliably track features of interests without visible distortions or noise at mesh interfaces. Simple threshold adaptation criteria for the geopotential height and the relative vorticity are assessed.Comment: 25 pages, 11 figures, preprin

Molecular subtyping of bladder cancer using Kohonen self-organizing maps

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6–5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3–11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering

A multidecadal simulation of Atlantic tropical cyclones using a variable‐resolution global atmospheric general circulation model

Using a variable‐resolution option within the National Center for Atmospheric Research/Department of Energy Community Atmosphere Model (CAM) Spectral Element (SE) global model, a refined nest at 0.25° (∼28 km) horizontal resolution located over the North Atlantic is embedded within a global 1° (∼111 km) grid. The grid is designed such that fine grid cells are located where tropical cyclones (TCs) are observed to occur during the Atlantic TC season (June–November). Two simulations are compared, one with refinement and one control case with no refinement (globally uniform 1° grid). Both simulations are integrated for 23 years using Atmospheric Model Intercomparison Protocols. TCs are tracked using an objective detection algorithm. The variable‐resolution simulation produces significantly more TCs than the unrefined simulation. Storms that do form in the refined nest are much more intense, with multiple storms strengthening to Saffir‐Simpson category 3 intensity or higher. Both count and spatial distribution of TC genesis and tracks in the variable‐resolution simulation are well matched to observations and represent significant improvements over the unrefined simulation. Some degree of interannual skill is noted, with the variable‐resolution grid able to reproduce the observed connection between Atlantic TCs and the El Niño‐Southern Oscillation (ENSO). It is shown that Genesis Potential Index (GPI) is well matched between the refined and unrefined simulations, implying that the introduction of variable‐resolution does not affect the synoptic environment. Potential “upscale” effects are noted in the variable‐resolution simulation, suggesting stronger TCs in refined nests may play a role in meridional transport of momentum, heat, and moisture. Key Points Variable‐resolution models can improve the representation of tropical cyclones CAM produces realistic Atlantic TC climatology at 0.25° resolution Addition of local refinement in CAM does not impact synoptic scalesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109331/1/jame20104.pd

A mutated dph3 gene causes sensitivity of Schizosaccharomyces pombe cells to cytotoxic agents

Dph3 is involved in diphthamide modification of the eukaryotic translation elongation factor eEF2 and in Elongator-mediated modifications of tRNAs, where a 5-methoxycarbonyl-methyl moiety is added to wobble uridines. Lack of such modifications affects protein synthesis due to inaccurate translation of mRNAs at ribosomes. We have discovered that integration of markers at the msh3 locus of Schizosaccharomyces pombe impaired the function of the nearby located dph3 gene. Such integrations rendered cells sensitive to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. We constructed dph3 and msh3 strains with mutated ATG start codons (ATGmut), which allowed investigating drug sensitivity without potential interference by marker insertions. The dph3- ATGmut and a dph3::loxP-ura4-loxM gene disruption strain, but not msh3-ATGmut, turned out to be sensitive to hydroxyurea and methyl methanesulfonate, likewise the strains with cassettes integrated at the msh3 locus. The fungicide sordarin, which inhibits diphthamide modified eEF2 of Saccharomyces cerevisiae, barely affected survival of wild type and msh3Δ S. pombe cells, while the dph3Δ mutant was sensitive. The msh3-ATG mutation, but not dph3Δ or the dph3-ATG mutation caused a defect in mating-type switching, indicating that the ura4 marker at the dph3 locus did not interfere with Msh3 function. We conclude that Dph3 is required for cellular resistance to the fungicide sordarin and to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. This is likely mediated by efficient translation of proteins in response to DNA damage and replication stress

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Abstract Although Candida glabrata is an important human pathogenic yeast, its pathogenicity mechanisms are largely unknown. Immune evasion strategies seem to play key roles during infection, since very little inflammation is observed in mouse models. Furthermore, C. glabrata multiplies intracellularly after engulfment by macrophages. In this study, we sought to identify the strategies that enable C. glabrata to survive phagosome biogenesis and antimicrobial activities within human monocyte-derived macrophages. We show that, despite significant intracellular proliferation, macrophage damage or apoptosis was not apparent, and production of reactive oxygen species was inhibited. Additionally, with the exception of GM-CSF, levels of pro- and anti-inflammatory cytokines were only marginally increased. We demonstrate that adhesion to and internalization by macrophages occur within minutes, and recruitment of endosomal early endosomal Ag 1 and lysosomal-associated membrane protein 1 indicates phagosome maturation. However, phagosomes containing viable C. glabrata, but not heat-killed yeasts, failed to recruit cathepsin D and were only weakly acidified. This inhibition of acidification did not require fungal viability, but it had a heat-sensitive surface attribute. Therefore, C. glabrata modifies the phagosome into a nonacidified environment and multiplies until the host cells finally lyse and release the fungi. Our results suggest persistence of C. glabrata within macrophages as a possible immune evasion strategy.</jats:p

Polyglycerol citrate: A novel coating and inoculation material for soybean seeds.

ABSTRACT The microbial inoculation of legumes such as soybeans is crucial for thriving plant growth due to symbiotic nitrogen (N) fixation and biological plant N fertilization. Soybean requires microbial pre-inoculation before sowing using the rhizobia strain Bradyrhizobium japonicum. Peat is typical for this purpose, although not sustainable since it is a finite resource. Here, we propose a straightforwarding route to prepare and apply polyglycerol-citrate polymer (PGC), a biodegradable and fully renewable polymer, as a carrier for Bradyrhizobium japonicum inoculants for soybeans. This novel eco-friendly polymer combines the advantages of a polymeric, water-soluble structure based on biopolymers, which can protect the inoculant cells during the seed inoculation process, with protective properties of glycerol for bacterial cells and the contribution of citric acid for metabolic processes. A greenhouse study was conducted using soybean seeds coated with three different proportions of PGC with B. japonicum planted in a sand substrate free of external interference. Comparative results of N content and δ15N signature in soybean plant parts calculated from the natural abundance method associated with viability tests showed equal or superior symbiotic performance and nitrogen fixation rates to peat-based inoculants, considered the goldstandard carrier for inoculants. It ensured the shelf life of the inoculant formulations, offering convenience for farmers and environmental benefits through reduced fertilization

Physics–Dynamics Coupling in weather, climate and Earth system models: Challenges and recent progress

This is the final version. Available from American Meteorological Society via the DOI in this record.Numerical weather, climate, or Earth system models involve the coupling of components. At a broad level, these components can be classified as the resolved fluid dynamics, unresolved fluid dynamical aspects (i.e., those represented by physical parameterizations such as subgrid-scale mixing), and nonfluid dynamical aspects such as radiation and microphysical processes. Typically, each component is developed, at least initially, independently. Once development is mature, the components are coupled to deliver a model of the required complexity. The implementation of the coupling can have a significant impact on the model. As the error associated with each component decreases, the errors introduced by the coupling will eventually dominate. Hence, any improvement in one of the components is unlikely to improve the performance of the overall system. The challenges associated with combining the components to create a coherent model are here termed physics–dynamics coupling. The issue goes beyond the coupling between the parameterizations and the resolved fluid dynamics. This paper highlights recent progress and some of the current challenges. It focuses on three objectives: to illustrate the phenomenology of the coupling problem with references to examples in the literature, to show how the problem can be analyzed, and to create awareness of the issue across the disciplines and specializations. The topics addressed are different ways of advancing full models in time, approaches to understanding the role of the coupling and evaluation of approaches, coupling ocean and atmosphere models, thermodynamic compatibility between model components, and emerging issues such as those that arise as model resolutions increase and/or models use variable resolutions.Natural Environment Research Council (NERC)National Science FoundationDepartment of Energy Office of Biological and Environmental ResearchPacific Northwest National Laboratory (PNNL)DOE Office of Scienc