Towards an Output-based Re-meshing for Turbomachinery Applications

The truncation error estimation methodology using topologically inconsistent fine and coarse meshes was presented. Estimated truncation error was weighted with an adjoint solution to obtain a robust output-based adaptation sensor. Re-meshing using Boxer and output-based sensor field was successfully applied to the simple cube test case showing almost an order of magnitude cost function error reduction as compared to the uniformly refined grid. More application examples are required including a more realistic turbulent cases e.g. turbine stator in order to investigate how useful is the methodology in practice. The key challenge for viscous flows is related to the treatment of boundary layer when performing re-meshing with Boxe

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Pursuing High Performance in Rural Health Care

Rural Futures Lab Foundation Papers are intended to present current thinking on the economic drivers and opportunities that will shape the future of rural America. They provide the foundation upon which it will be possible to answer the question that drives the Lab’s work—What has to happen today in order to achieve positive rural outcomes tomorrow

Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight

We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel

Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies

To facilitate whole-genome association studies (WGAS), several high-density SNP genotyping arrays have been developed. Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays. Ideally, such evaluations would be done on a SNP set and a cohort of individuals that are both independently sampled from the original SNPs and individuals used in developing the arrays. Without utilization of an independent test set, previous estimates of genetic coverage and statistical power may be subject to an overfitting bias. Additionally, the SNP arrays' statistical power in WGAS has not been systematically assessed on real traits. One robust setting for doing so is to evaluate statistical power on thousands of traits measured from a single set of individuals. In this study, 359 newly sampled Americans of European descent were genotyped using both Affymetrix 500K (Affx500K) and Illumina 650Y (Ilmn650K) SNP arrays. From these data, we were able to obtain estimates of genetic coverage, which are robust to overfitting, by constructing an independent test set from among these genotypes and individuals. Furthermore, we collected liver tissue RNA from the participants and profiled these samples on a comprehensive gene expression microarray. The RNA levels were used as a large-scale set of quantitative traits to calibrate the relative statistical power of the commercial arrays. Our genetic coverage estimates are lower than previous reports, providing evidence that previous estimates may be inflated due to overfitting. The Ilmn650K platform showed reasonable power (50% or greater) to detect SNPs associated with quantitative traits when the signal-to-noise ratio (SNR) is greater than or equal to 0.5 and the causal SNP's minor allele frequency (MAF) is greater than or equal to 20% (N = 359). In testing each of the more than 40,000 gene expression traits for association to each of the SNPs on the Ilmn650K and Affx500K arrays, we found that the Ilmn650K yielded 15% times more discoveries than the Affx500K at the same false discovery rate (FDR) level

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

Fundamental spray and combustion measurements of soy methyl-ester biodiesel

Although biodiesel has begun to penetrate the fuel market, its effect on injection processes, combustion and emission formation under diesel engine conditions remains somewhat unclear. Typical exhaust measurements from engines running biodiesel indicate that particulate matter, carbon monoxide and unburnt hydrocarbons are decreased, whereas nitrogen oxide emissions tend to be increased. However, these observations are the result of complex interactions between physical and chemical processes occurring in the combustion chamber, for which understanding is still needed. To characterize and decouple the physical and chemical influences of biodiesel on spray mixing, ignition, combustion and soot formation, a soy methyl-ester (SME) biodiesel is injected into a constant-volume combustion facility under diesel-like operating conditions. A range of optical diagnostics is performed, comparing biodiesel to a conventional #2 diesel at the same injection and ambient conditions. Schlieren high-speed imaging shows virtually the same vapour-phase penetration for the two fuels, while simultaneous Mie-scatter imaging shows that the maximum liquid-phase penetration of biodiesel is higher than diesel. Differences in the liquid-phase penetration are expected because of the different boiling-point temperatures of the two fuels. However, the different liquid-phase penetration does not affect overall mixing rate and downstream vapour-phase penetration because each fuel spray has similar momentum and spreading angle. For the biodiesel and diesel samples used in this study, the ignition delay and lift-off length are only slightly less for biodiesel compared to diesel, consistent with the fuel cetane number (51 for biodiesel, 46 for diesel). Because of the similarity in lift-off length, the differences in equivalence ratio distribution at the lift-off length are mainly affected by the oxygen content of the fuels. For biodiesel, the equivalence ratio is reduced, which, along with the fuel molecular structure and oxygen content, significantly affects soot formation downstream. Spatially resolved soot volume fraction measurements obtained by combining line-of-sight laser extinction measurements with planar laser-induced incandescence imaging show that the soot concentration can be reduced by an order of magnitude for biodiesel. These integrated measurements of spray mixing, combustion and quantitative soot concentration provide new validation data for the development of computational fluid dynamics spray, combustion and soot formation models suitable for the latest biofuels.This work was supported by the Spanish Ministry of Science and Innovation for Jean-Guillaume Nerva's visiting research, through the OPTICOMB project [TRA2007-67961-C03-01].Nerva, J.; Genzale, CL.; Kook, S.; García Oliver, JM.; Pickett, LM. (2013). Fundamental spray and combustion measurements of soy methyl-ester biodiesel. International Journal of Engine Research. 14(4):373-390. https://doi.org/10.1177/1468087412456688S373390144(2009). World Energy Outlook 2009. World Energy Outlook. doi:10.1787/weo-2009-enMonyem, A., & H. Van Gerpen, J. (2001). The effect of biodiesel oxidation on engine performance and emissions. Biomass and Bioenergy, 20(4), 317-325. doi:10.1016/s0961-9534(00)00095-7LAPUERTA, M., ARMAS, O., & RODRIGUEZFERNANDEZ, J. (2008). Effect of biodiesel fuels on diesel engine emissions. Progress in Energy and Combustion Science, 34(2), 198-223. doi:10.1016/j.pecs.2007.07.001Fisher, B. T., Knothe, G., & Mueller, C. J. (2010). Liquid-Phase Penetration under Unsteady In-Cylinder Conditions: Soy- and Cuphea-Derived Biodiesel Fuels Versus Conventional Diesel. Energy & Fuels, 24(9), 5163-5180. doi:10.1021/ef100594pFang, T., Lin, Y.-C., Foong, T. M., & Lee, C. (2009). Biodiesel combustion in an optical HSDI diesel engine under low load premixed combustion conditions. Fuel, 88(11), 2154-2162. doi:10.1016/j.fuel.2009.02.033Pastor, J. V., García-Oliver, J. M., Nerva, J.-G., & Giménez, B. (2011). Fuel effect on the liquid-phase penetration of an evaporating spray under transient diesel-like conditions. Fuel, 90(11), 3369-3381. doi:10.1016/j.fuel.2011.05.006Fisher, B. T., & Mueller, C. J. (2010). Liquid penetration length of heptamethylnonane and trimethylpentane under unsteady in-cylinder conditions. Fuel, 89(10), 2673-2696. doi:10.1016/j.fuel.2010.04.024Kim, H. J., Park, S. H., Suh, H. K., & Lee, C. S. (2009). Atomization and Evaporation Characteristics of Biodiesel and Dimethyl Ether Compared to Diesel Fuel in a High-Pressure Injection System. Energy & Fuels, 23(3), 1734-1742. doi:10.1021/ef800811gSuh, H. K., Roh, H. G., & Lee, C. S. (2008). Spray and Combustion Characteristics of Biodiesel∕Diesel Blended Fuel in a Direct Injection Common-Rail Diesel Engine. Journal of Engineering for Gas Turbines and Power, 130(3). doi:10.1115/1.2835354Pickett, L. M., & Siebers, D. L. (2006). Soot Formation in Diesel Fuel Jets Near the Lift-Off Length. International Journal of Engine Research, 7(2), 103-130. doi:10.1243/146808705x57793Pickett, L. M., Kook, S., Persson, H., & Andersson, Ö. (2009). Diesel fuel jet lift-off stabilization in the presence of laser-induced plasma ignition. Proceedings of the Combustion Institute, 32(2), 2793-2800. doi:10.1016/j.proci.2008.06.082Yoo, C. S., Richardson, E. S., Sankaran, R., & Chen, J. H. (2011). A DNS study on the stabilization mechanism of a turbulent lifted ethylene jet flame in highly-heated coflow. Proceedings of the Combustion Institute, 33(1), 1619-1627. doi:10.1016/j.proci.2010.06.147Pastor, J. V., Payri, R., Gimeno, J., & Nerva, J. G. (2009). Experimental Study on RME Blends: Liquid-Phase Fuel Penetration, Chemiluminescence, and Soot Luminosity in Diesel-Like Conditions. Energy & Fuels, 23(12), 5899-5915. doi:10.1021/ef9007328Benajes, J., Molina, S., Novella, R., & Amorim, R. (2010). Study on Low Temperature Combustion for Light-Duty Diesel Engines. Energy & Fuels, 24(1), 355-364. doi:10.1021/ef900832cPickett, L. M., & Siebers, D. L. (2002). An investigation of diesel soot formation processes using micro-orifices. Proceedings of the Combustion Institute, 29(1), 655-662. doi:10.1016/s1540-7489(02)80084-0Siebers, D. L., & Pickett, L. M. (2004). Injection Pressure and Orifice Diameter Effects on Soot in DI Diesel Fuel Jets. Thermo- and Fluid Dynamic Processes in Diesel Engines 2, 109-132. doi:10.1007/978-3-662-10502-3_7Pickett, L. M., & Siebers, D. L. (2004). Soot in diesel fuel jets: effects of ambient temperature, ambient density, and injection pressure. Combustion and Flame, 138(1-2), 114-135. doi:10.1016/j.combustflame.2004.04.006Cheng, A. S., Upatnieks, A., & Mueller, C. J. (2006). Investigation of the impact of biodiesel fuelling on NOx emissions using an optical direct injection diesel engine. International Journal of Engine Research, 7(4), 297-318. doi:10.1243/14680874jer05005Cheng, A. S. (Ed), Upatnieks, A., & Mueller, C. J. (2007). Investigation of Fuel Effects on Dilute, Mixing-Controlled Combustion in an Optical Direct-Injection Diesel Engine. Energy & Fuels, 21(4), 1989-2002. doi:10.1021/ef0606456Klein-Douwel, R. J. H., Donkerbroek, A. J., van Vliet, A. P., Boot, M. D., Somers, L. M. T., Baert, R. S. G., … ter Meulen, J. J. (2009). Soot and chemiluminescence in diesel combustion of bio-derived, oxygenated and reference fuels. Proceedings of the Combustion Institute, 32(2), 2817-2825. doi:10.1016/j.proci.2008.06.140Fang, T., & Lee, C. F. (2009). Bio-diesel effects on combustion processes in an HSDI diesel engine using advanced injection strategies. Proceedings of the Combustion Institute, 32(2), 2785-2792. doi:10.1016/j.proci.2008.07.031Payri, F., Pastor, J. V., Nerva, J.-G., & Garcia-Oliver, J. M. (2011). Lift-Off Length and KL Extinction Measurements of Biodiesel and Fischer-Tropsch Fuels under Quasi-Steady Diesel Engine Conditions. SAE International Journal of Engines, 4(2), 2278-2297. doi:10.4271/2011-24-0037Kook, S., & Pickett, L. M. (2012). Liquid length and vapor penetration of conventional, Fischer–Tropsch, coal-derived, and surrogate fuel sprays at high-temperature and high-pressure ambient conditions. Fuel, 93, 539-548. doi:10.1016/j.fuel.2011.10.004Settles, G. S. (2001). Schlieren and Shadowgraph Techniques. doi:10.1007/978-3-642-56640-0Pickett, L. M., Manin, J., Genzale, C. L., Siebers, D. L., Musculus, M. P. B., & Idicheria, C. A. (2011). Relationship Between Diesel Fuel Spray Vapor Penetration/Dispersion and Local Fuel Mixture Fraction. SAE International Journal of Engines, 4(1), 764-799. doi:10.4271/2011-01-0686MUSCULUS, M., & PICKETT, L. (2005). Diagnostic considerations for optical laser-extinction measurements of soot in high-pressure transient combustion environments. Combustion and Flame, 141(4), 371-391. doi:10.1016/j.combustflame.2005.01.013Williams, T. C., Shaddix, C. R., Jensen, K. A., & Suo-Anttila, J. M. (2007). Measurement of the dimensionless extinction coefficient of soot within laminar diffusion flames. International Journal of Heat and Mass Transfer, 50(7-8), 1616-1630. doi:10.1016/j.ijheatmasstransfer.2006.08.024Kook, S., & Pickett, L. M. (2011). Soot volume fraction and morphology of conventional and surrogate jet fuel sprays at 1000-K and 6.7-MPa ambient conditions. Proceedings of the Combustion Institute, 33(2), 2911-2918. doi:10.1016/j.proci.2010.05.073De Francqueville, L., Bruneaux, G., & Thirouard, B. (2010). Soot Volume Fraction Measurements in a Gasoline Direct Injection Engine by Combined Laser Induced Incandescence and Laser Extinction Method. SAE International Journal of Engines, 3(1), 163-182. doi:10.4271/2010-01-0346Musculus, M. P. B., & Kattke, K. (2009). Entrainment Waves in Diesel Jets. SAE International Journal of Engines, 2(1), 1170-1193. doi:10.4271/2009-01-1355Desantes, J. M., Pastor, J. V., García-Oliver, J. M., & Pastor, J. M. (2009). A 1D model for the description of mixing-controlled reacting diesel sprays. Combustion and Flame, 156(1), 234-249. doi:10.1016/j.combustflame.2008.10.008Idicheria, C. A., & Pickett, L. M. (2011). Ignition, soot formation, and end-of-combustion transients in diesel combustion under high-EGR conditions. International Journal of Engine Research, 12(4), 376-392. doi:10.1177/1468087411399505Aizawa, T., & Kosaka, H. (2008). Investigation of early soot formation process in a diesel spray flame via excitation—emission matrix using a multi-wavelength laser source. International Journal of Engine Research, 9(1), 79-97. doi:10.1243/14680874jer01407Bruneaux, G. (2008). Combustion structure of free and wall-impinging diesel jets by simultaneous laser-induced fluorescence of formaldehyde, poly-aromatic hydrocarbons, and hydroxides. International Journal of Engine Research, 9(3), 249-265. doi:10.1243/14680874jer0010

EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2

The provisional EULAR recommendations address several aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus, and the disease caused by SARS-CoV-2, COVID-19 and are meant for patients with rheumatic and musculoskeletal diseases (RMD) and their caregivers. A task force of 20 members was convened by EULAR that met several times by videoconferencing in April 2020. The task force finally agreed on five overarching principles and 13 recommendations covering four generic themes: (1) General measures and prevention of SARS-CoV-2 infection. (2) The management of RMD when local measures of social distancing are in effect. (3) The management of COVID-19 in the context of RMD. (4) The prevention of infections other than SARS-CoV-2. EULAR considers this set of recommendations as a 'living document' and a starting point, which will be updated as soon as promising new developments with potential impact on the care of patients with RMD become available

Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS