Sketch-To-Solution: An Exploration of Viscous CFD with Automatic Grids

Numerical simulation of the Reynolds-averaged NavierStokes (RANS) equations has become a critical tool for the design of aerospace vehicles. However, the issues that affect the grid convergence of three dimensional RANS solutions are not completely understood, as documented in the AIAA Drag Prediction Workshop series. Grid adaption methods have the potential for increasing the automation and discretization error control of RANS solutions to impact the aerospace design and certification process. The realization of the CFD Vision 2030 Study includes automated management of errors and uncertainties of physics-based, predictive modeling that can set the stage for ensuring a vehicle is in compliance with a regulation or specification by using analysis without demonstration in flight test (i.e., certification or qualification by analysis). For example, the Cart3D inviscid analysis package has automated Cartesian cut-cell gridding with output-based error control. Fueled by recent advances in the fields of anisotropic grid adaptation, error estimation, and geometry modeling, a similar work flow is explored for viscous CFD simulations; where a CFD application engineer provides geometry, boundary conditions, and flow parameters, and the sketch-to-solution process yields a CFD simulation through automatic, error-based, grid adaptation

Results of the Anaconda endovascular graft in abdominal aortic aneurysm with a severe angulated infrarenal neck

Objective: Proximal neck anatomy of an abdominal aortic aneurysm (AAA), especially a severe angulated neck of more than 60 degrees, predicts adverse outcome in endovascular aneurysm repair. In the present study, we evaluate the feasibility of the use of the Anaconda endovascular graft (Vascutec, Terumo, Inchinnan, Scotland) for treating infrarenal AAA with a severe angulated neck (>60 degrees) and report the midterm outcomes. Methods: In total, nine Dutch hospitals participated in this prospective cohort study. From December 2005 to January 2011, a total of 36 AAA patients, 30 men and six women, were included. Mean and median follow-up were both 40 months. Results: Mean infrarenal neck angulation was 82 degrees. Successful deployment was reached in 34 of 36 patients. Primary technical success was achieved in 30 of 36 patients (83%). There was no aneurysm-related death. Four-year primary clinical success was 69%. In the first year, eight clinical failures were reported including four leg occlusions which could be solved using standard procedures. After the first year, three patients with additional failures occurred; two of them were leg occlusions. Four patients needed conversion to open AAA exclusion. In six of 36 patients, one or more reinterventions were necessary. Three of them were performed for occlusion of one Anaconda leg and two were for occlusion of the body. Conclusions: The use of the Anaconda endovascular graft in AAA with a severe angulated infrarenal neck is feasible but has its side effects. Most clinical failures occur in the first year. Thereafter, few problems occur, and midterm results are acceptable. Summarizing the present experiences, we conclude that open AAA repair is still a preferable option in patients with challenging aortic neck anatomy and fit for open surgery

Tactile-visual links in exogenous spatial attention under different postures: convergent evidence from psychophysics and ERPs

Tactile-visual links in spatial attention were examined by presenting spatially nonpredictive tactile cues to the left or right hand, shortly prior to visual targets in the left or right hemifield. To examine the spatial coordinates of any cross-modal links, different postures were examined. The hands were either uncrossed, or crossed so that the left hand lay in the right visual field and vice versa. Visual judgments were better on the side where the stimulated hand lay, though this effect was somewhat smaller with longer intervals between cue and target, and with crossed hands. Event-related brain potentials (ERPs) showed a similar pattern. Larger amplitude occipital N1 components were obtained for visual events on the same side as the preceding tactile cue, at ipsilateral electrode sites. Negativities in the Nd2 interval at midline and lateral central sites, and in the Nd1 interval at electrode Pz, were also enhanced for the cued side. As in the psychophysical results, ERP cueing effects during the crossed posture were determined by the side of space in which the stimulated hand lay, not by the anatomical side of the initial hemispheric projection for the tactile cue. These results demonstrate that crossmodal links in spatial attention can influence sensory brain responses as early as the N1, and that these links operate in a spatial frame-of-reference that can remap between the modalities across changes in posture

Glassy Vortex State in a Two-Dimensional Disordered XY-Model

The two-dimensional XY-model with random phase-shifts on bonds is studied. The analysis is based on a renormalization group for the replicated system. The model is shown to have an ordered phase with quasi long-range order. This ordered phase consists of a glass-like region at lower temperatures and of a non-glassy region at higher temperatures. The transition from the disordered phase into the ordered phase is not reentrant and is of a new universality class at zero temperature. In contrast to previous approaches the disorder strength is found to be renormalized to larger values. Several correlation functions are calculated for the ordered phase. They allow to identify not only the transition into the glassy phase but also an additional crossover line, where the disconnected vortex correlation changes its behavior on large scales non-analytically. The renormalization group approach yields the glassy features without a breaking of replica symmetry.Comment: latex 12 pages with 3 figures, using epsf.sty and multicol.st

Developing European conservation and mitigation tools for pollination services: approaches of the STEP (Status and Trends of European Pollinators) project

Pollinating insects form a key component of European biodiversity, and provide a vital ecosystem service to crops and wild plants. There is growing evidence of declines in both wild and domesticated pollinators, and parallel declines in plants relying upon them. The STEP project (Status and Trends of European Pollinators, 2010-2015, www.stepproject.net) is documenting critical elements in the nature and extent of these declines, examining key functional traits associated with pollination deficits, and developing a Red List for some European pollinator groups. Together these activities are laying the groundwork for future pollinator monitoring programmes. STEP is also assessing the relative importance of potential drivers of pollinator declines, including climate change, habitat loss and fragmentation, agrochemicals, pathogens, alien species, light pollution, and their interactions. We are measuring the ecological and economic impacts of declining pollinator services and floral resources, including effects on wild plant populations, crop production and human nutrition. STEP is reviewing existing and potential mitigation options, and providing novel tests of their effectiveness across Europe. Our work is building upon existing and newly developed datasets and models, complemented by spatially-replicated campaigns of field research to fill gaps in current knowledge. Findings are being integrated into a policy-relevant framework to create evidence-based decision support tools. STEP is establishing communication links to a wide range of stakeholders across Europe and beyond, including policy makers, beekeepers, farmers, academics and the general public. Taken together, the STEP research programme aims to improve our understanding of the nature, causes, consequences and potential mitigation of declines in pollination services at local, national, continental and global scales

One-Sided Position-Dependent Smoothness-Increasing Accuracy-Conserving (SIAC) Filtering Over Uniform and Non-Uniform Meshes

In this paper, we introduce a new position-dependent Smoothness-Increasing Accuracy-Conserving (SIAC) filter that retains the benefits of position dependence while ameliorating some of its shortcomings. As in the previous position-dependent filter, our new filter can be applied near domain boundaries, near a discontinuity in the solution, or at the interface of different mesh sizes; and as before, in general, it numerically enhances the accuracy and increases the smoothness of approximations obtained using the discontinuous Galerkin (dG) method. However, the previously proposed position-dependent one-sided filter had two significant disadvantages: (1) increased computational cost (in terms of function evaluations), brought about by the use of $4k+1$ central B-splines near a boundary (leading to increased kernel support) and (2) increased numerical conditioning issues that necessitated the use of quadruple precision for polynomial degrees of $k\ge 3$ for the reported accuracy benefits to be realizable numerically. Our new filter addresses both of these issues --- maintaining the same support size and with similar function evaluation characteristicsas the symmetric filter in a way that has better numerical conditioning --- making it, unlike its predecessor, amenable for GPU computing. Our new filter was conceived by revisiting the original error analysis for superconvergence of SIAC filters and by examining the role of the B-splines and their weights in the SIAC filtering kernel. We demonstrate, in the uniform mesh case, that our new filter is globally superconvergent for $k=1$ and superconvergent in the interior (e.g., region excluding the boundary) for $k\ge2$. Furthermore, we present the first theoretical proof of superconvergence for postprocessing over smoothly varying meshes, and explain the accuracy-order conserving nature of this new filter when applied to certain non-uniform meshes cases. We provide numerical examples supporting our theoretical results and demonstrating that our new filter, in general, enhances the smoothness and accuracy of the solution. Numerical results are presented for solutions of both linear and nonlinear equation solved on both uniform and non-uniform one- and two-dimensional meshes

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer