Experimental study of influence of Liquefied Petroleum Gas addition in Hydrotreated Vegetable Oil fuel on ignition delay, flame lift off length and soot emission under diesel-like conditions

[EN] The fundamental behaviour on ignition and combustion characteristics of blends of Hydrotreated Vegetable Oil and Liquid Petroleum Gas was investigated in a constant high pressure, high temperature combustion chamber, using a prototype lab-scale injection system adapted from a conventional common-rail system to conduct the injection events, ensuring that fuel was liquid at any point of the injection system and avoiding the formation of fuel vapour bubbles that could alter the injected fuel behaviour. The ignition delay, flame lift-off length and the soot formation were studied by means of high-speed imaging techniques, for different operating conditions. The aim of the work is to characterize the effect of Hydrotreated Vegetable Oil-Liquid Petroleum Gas blend ratios on the previously mentioned parameters. Experimental results show that the behaviour of the fuel blends follow the expected trends of conventional diesel type fuels when varying ambient temperature, density and injection pressure. Hydrotreated Vegetable Oil, being the highest reactivity fraction, controls auto ignition of the blend. However, Liquid Petroleum Gas acts as combustion inhibitor increasing both ignition delay and lift-off length as its ratio in the blend increases. As a consequence, the differences observed in terms of flame radiation suggest that increasing Liquid Petroleum Gas fraction reduces soot formation as it promotes a higher air/mixture.The authors acknowledge that this research work has been partly funded by the Government of Spain and FEDER under TRANCO project (TRA2017-87694-R) and by Universitat Politècnica de València through the Programa de Ayudas de Investigación y Desarrollo (PAID01-18) program.Pastor, JV.; García Martínez, A.; Mico Reche, C.; Garcia-Carrero, AA. (2020). Experimental study of influence of Liquefied Petroleum Gas addition in Hydrotreated Vegetable Oil fuel on ignition delay, flame lift off length and soot emission under diesel-like conditions. Fuel. 260:1-11. https://doi.org/10.1016/j.fuel.2019.116377S111260Roadmap to a Single European Transport Area – Towards a competitive and resource efficient. Transport System, White Paper COM(2011):144–final.Sheehan J, Camobreco V, Duffield J, Graboski M, Shapouri H. An Overview of Biodiesel and Petroleum Diesel Life Cycles, NREL/TP-580-24772.Hasan, M. M., & Rahman, M. M. (2017). Performance and emission characteristics of biodiesel–diesel blend and environmental and economic impacts of biodiesel production: A review. Renewable and Sustainable Energy Reviews, 74, 938-948. doi:10.1016/j.rser.2017.03.045Bhardwaj, O. P., Kolbeck, A. F., Kkoerfer, T., & Honkanen, M. (2013). Potential of Hydrogenated Vegetable Oil (HVO) in Future High Efficiency Combustion System. SAE International Journal of Fuels and Lubricants, 6(1), 157-169. doi:10.4271/2013-01-1677Chakraborty, A., Roy, S., & Banerjee, R. (2016). An experimental based ANN approach in mapping performance-emission characteristics of a diesel engine operating in dual-fuel mode with LPG. Journal of Natural Gas Science and Engineering, 28, 15-30. doi:10.1016/j.jngse.2015.11.024Aatola, H., Larmi, M., Sarjovaara, T., & Mikkonen, S. (2008). Hydrotreated Vegetable Oil (HVO) as a Renewable Diesel Fuel: Trade-off between NOx, Particulate Emission, and Fuel Consumption of a Heavy Duty Engine. SAE International Journal of Engines, 1(1), 1251-1262. doi:10.4271/2008-01-2500Neste Oil, Hydrotreated vegetable oil, premium renewable biofuel for diesel engines, 2014.Singh, D., Subramanian, K. A., Bal, R., Singh, S. P., & Badola, R. (2018). Combustion and emission characteristics of a light duty diesel engine fueled with hydro-processed renewable diesel. Energy, 154, 498-507. doi:10.1016/j.energy.2018.04.139Zhong, W., Pachiannan, T., He, Z., Xuan, T., & Wang, Q. (2019). Experimental study of ignition, lift-off length and emission characteristics of diesel/hydrogenated catalytic biodiesel blends. Applied Energy, 235, 641-652. doi:10.1016/j.apenergy.2018.10.115Tira, H. S., Herreros, J. M., Tsolakis, A., & Wyszynski, M. L. (2014). Influence of the addition of LPG-reformate and H2 on an engine dually fuelled with LPG–diesel, –RME and –GTL Fuels. Fuel, 118, 73-82. doi:10.1016/j.fuel.2013.10.065Goto, S., Lee, D., Shakal, J., Harayama, N., Honjyo, F., & Ueno, H. (1999). Performance and Emissions of an LPG Lean-Burn Engine for Heavy Duty Vehicles. SAE Technical Paper Series. doi:10.4271/1999-01-1513Musthafa, M. M. (2019). A comparative study on coated and uncoated diesel engine performance and emissions running on dual fuel (LPG – biodiesel) with and without additive. Industrial Crops and Products, 128, 194-198. doi:10.1016/j.indcrop.2018.11.012Hashimoto, K., Ohta, H., Hirasawa, T., Arai, M., & Tamura, M. (2002). Evaluation of Ignition Quality of LPG with Cetane Number Improver. SAE Technical Paper Series. doi:10.4271/2002-01-0870Benajes, J., Molina, S., García, A., & Monsalve-Serrano, J. (2015). Effects of low reactivity fuel characteristics and blending ratio on low load RCCI (reactivity controlled compression ignition) performance and emissions in a heavy-duty diesel engine. Energy, 90, 1261-1271. doi:10.1016/j.energy.2015.06.088Benajes, J., García, A., Monsalve-Serrano, J., & Boronat, V. (2016). Dual-Fuel Combustion for Future Clean and Efficient Compression Ignition Engines. Applied Sciences, 7(1), 36. doi:10.3390/app7010036Benajes, J., García, A., Monsalve-Serrano, J., & Boronat, V. (2017). Achieving clean and efficient engine operation up to full load by combining optimized RCCI and dual-fuel diesel-gasoline combustion strategies. Energy Conversion and Management, 136, 142-151. doi:10.1016/j.enconman.2017.01.010Kokjohn, S. L., Hanson, R. M., Splitter, D. A., & Reitz, R. D. (2011). Fuel reactivity controlled compression ignition (RCCI): a pathway to controlled high-efficiency clean combustion. International Journal of Engine Research, 12(3), 209-226. doi:10.1177/1468087411401548Payri, R., Gimeno, J., Bardi, M., & Plazas, A. H. (2013). Study liquid length penetration results obtained with a direct acting piezo electric injector. Applied Energy, 106, 152-162. doi:10.1016/j.apenergy.2013.01.027Gimeno, J., Martí-Aldaraví, P., Carreres, M., & Peraza, J. E. (2018). Effect of the nozzle holder on injected fuel temperature for experimental test rigs and its influence on diesel sprays. International Journal of Engine Research, 19(3), 374-389. doi:10.1177/1468087417751531Pastor, J. V., García-Oliver, J. M., García, A., Micó, C., & Möller, S. (2016). Application of optical diagnostics to the quantification of soot in n-alkane flames under diesel conditions. Combustion and Flame, 164, 212-223. doi:10.1016/j.combustflame.2015.11.018Pastor, J., Garcia-Oliver, J. M., Garcia, A., & Nareddy, V. R. (2017). Characterization of Spray Evaporation and Mixing Using Blends of Commercial Gasoline and Diesel Fuels in Engine-Like Conditions. SAE Technical Paper Series. doi:10.4271/2017-01-0843Pastor, J. V., Payri, R., Garcia-Oliver, J. M., & Briceño, F. J. (2013). Schlieren Methodology for the Analysis of Transient Diesel Flame Evolution. SAE International Journal of Engines, 6(3), 1661-1676. doi:10.4271/2013-24-0041Siebers, D. L. (1998). Liquid-Phase Fuel Penetration in Diesel Sprays. SAE Technical Paper Series. doi:10.4271/980809ECN. Engine Combustion Network. https://ecn.sandia.gov/.Desantes, J. M., Pastor, J. V., García-Oliver, J. M., & Briceño, F. J. (2014). An experimental analysis on the evolution of the transient tip penetration in reacting Diesel sprays. Combustion and Flame, 161(8), 2137-2150. doi:10.1016/j.combustflame.2014.01.022Payri, R., Viera, J. P., Pei, Y., & Som, S. (2015). Experimental and numerical study of lift-off length and ignition delay of a two-component diesel surrogate. Fuel, 158, 957-967. doi:10.1016/j.fuel.2014.11.072Reyes, M., Tinaut, F. V., Giménez, B., & Pastor, J. V. (2018). Effect of hydrogen addition on the OH* and CH* chemiluminescence emissions of premixed combustion of methane-air mixtures. International Journal of Hydrogen Energy, 43(42), 19778-19791. doi:10.1016/j.ijhydene.2018.09.005Siebers, D. L., & Higgins, B. (2001). Flame Lift-Off on Direct-Injection Diesel Sprays Under Quiescent Conditions. SAE Technical Paper Series. doi:10.4271/2001-01-0530Benajes, J., Payri, R., Bardi, M., & Martí-Aldaraví, P. (2013). Experimental characterization of diesel ignition and lift-off length using a single-hole ECN injector. Applied Thermal Engineering, 58(1-2), 554-563. doi:10.1016/j.applthermaleng.2013.04.044Payri, R., Salvador, F. J., Manin, J., & Viera, A. (2016). Diesel ignition delay and lift-off length through different methodologies using a multi-hole injector. Applied Energy, 162, 541-550. doi:10.1016/j.apenergy.2015.10.118Kook, 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.2011.10.004Payri, R., García-Oliver, J. M., Xuan, T., & Bardi, M. (2015). A study on diesel spray tip penetration and radial expansion under reacting conditions. Applied Thermal Engineering, 90, 619-629. doi:10.1016/j.applthermaleng.2015.07.042Payri, R., Viera, J. P., Gopalakrishnan, V., & Szymkowicz, P. G. (2017). The effect of nozzle geometry over ignition delay and flame lift-off of reacting direct-injection sprays for three different fuels. Fuel, 199, 76-90. doi:10.1016/j.fuel.2017.02.075Pickett, L. M., Siebers, D. L., & Idicheria, C. A. (2005). Relationship Between Ignition Processes and the Lift-Off Length of Diesel Fuel Jets. SAE Technical Paper Series. doi:10.4271/2005-01-3843Xuan, T., Desantes, J. M., Pastor, J. V., & Garcia-Oliver, J. M. (2019). Soot temperature characterization of spray a flames by combined extinction and radiation methodology. Combustion and Flame, 204, 290-303. doi:10.1016/j.combustflame.2019.03.023Desantes, 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.2008.10.00

Experimental Study of the Influence of Gasoline-Diesel Blends on the Combustion Process and Soot Formation under Diesel Engine-Like Conditions

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Energy & Fuels, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.energyfuels.0c00091.[EN] Recent research has demonstrated that a reduction in pollutant emissions of diesel engines can be achieved by using high octane fuels such as gasoline, methane, or liquefied petroleum gas. Therefore, in this study, the focus was to investigate the influence of blends of diesel and gasoline on combustion characteristics such as ignition delay, rate of heat release, and lift-off length as well as the influence on soot formation. The experiments were carried out in a test rig with optical access which mimics a single-cylinder diesel engine. Four blends were tested: one blend with 100% diesel and then three diesel-gasoline blends with 30%, 50%, and70% gasoline. The blends were made in volumetric proportions and injected using a common rail injection system without any kind of modification. The ignition delay and the apparent heat release were obtained by means of the in-cylinder pressure signal. Furthermore, the combustion development and soot formation were studied using three optical techniques: OH* chemiluminescence, natural luminosity, and diffused back-illumination extinction imaging (DBI). Different engine operating conditions were analyzed. Results showed that ID increases with the gasoline content in the blend. Similarly, as the reacting time increased, the lift-off length was longer. On the other hand, the apparent rate of heat release decreased due to a reduction of the fuel injection rate, which depends on the density of the blend. In addition, differences in the flame radiation were also observed. Gasoline-diesel blends had less luminosity, which is related to less soot formation. To confirm this, the KL factor obtained from the DBI technique was determined, and it was concluded that increasing the gasoline fraction in the blend reduces soot formation.This research work has been partly funded by the Government of Spain and FEDER under TRANCO project (TRA2017-87694-R) and by Universitat Politecnica de Valencia through the Programa de Ayudas de Investigacion y Desarrollo (PAID-01-18 and PAID-06-18) program.Pastor, JV.; García Martínez, A.; Mico Reche, C.; Garcia-Carrero, AA. (2020). Experimental Study of the Influence of Gasoline-Diesel Blends on the Combustion Process and Soot Formation under Diesel Engine-Like Conditions. Energy & Fuels. 34(5):5589-5598. https://doi.org/10.1021/acs.energyfuels.0c00091S55895598345Murugesa Pandian, M., & Anand, K. (2018). Comparison of different low temperature combustion strategies in a light duty air cooled diesel engine. Applied Thermal Engineering, 142, 380-390. doi:10.1016/j.applthermaleng.2018.07.047Kokjohn, S. L., Hanson, R. M., Splitter, D. A., & Reitz, R. D. (2011). Fuel reactivity controlled compression ignition (RCCI): a pathway to controlled high-efficiency clean combustion. International Journal of Engine Research, 12(3), 209-226. doi:10.1177/1468087411401548Kokjohn, S. L., Hanson, R. M., Splitter, D. A., & Reitz, R. D. (2009). Experiments and Modeling of Dual-Fuel HCCI and PCCI Combustion Using In-Cylinder Fuel Blending. SAE International Journal of Engines, 2(2), 24-39. doi:10.4271/2009-01-2647Benajes, J., García, A., Monsalve-Serrano, J., & Boronat, V. (2016). Dual-Fuel Combustion for Future Clean and Efficient Compression Ignition Engines. Applied Sciences, 7(1), 36. doi:10.3390/app7010036Benajes, J., García, A., Monsalve-Serrano, J., & Boronat, V. (2017). Achieving clean and efficient engine operation up to full load by combining optimized RCCI and dual-fuel diesel-gasoline combustion strategies. Energy Conversion and Management, 136, 142-151. doi:10.1016/j.enconman.2017.01.010Benajes, J., García, A., Monsalve-Serrano, J., & Boronat, V. (2017). An investigation on the particulate number and size distributions over the whole engine map from an optimized combustion strategy combining RCCI and dual-fuel diesel-gasoline. Energy Conversion and Management, 140, 98-108. doi:10.1016/j.enconman.2017.02.073Benajes, J., García, A., Monsalve-Serrano, J., & Boronat, V. (2017). Gaseous emissions and particle size distribution of dual-mode dual-fuel diesel-gasoline concept from low to full load. Applied Thermal Engineering, 120, 138-149. doi:10.1016/j.applthermaleng.2017.04.005Dempsey, A. B., Curran, S., & Reitz, R. D. (2015). Characterization of Reactivity Controlled Compression Ignition (RCCI) Using Premixed Gasoline and Direct-Injected Gasoline with a Cetane Improver on a Multi-Cylinder Engine. SAE International Journal of Engines, 8(2), 859-877. doi:10.4271/2015-01-0855Bendu, H., & Murugan, S. (2014). Homogeneous charge compression ignition (HCCI) combustion: Mixture preparation and control strategies in diesel engines. Renewable and Sustainable Energy Reviews, 38, 732-746. doi:10.1016/j.rser.2014.07.019Bermúdez, V., García, J. M., Juliá, E., & Martínez, S. (2003). Engine with Optically Accessible Cylinder Head: A Research Tool for Injection and Combustion Processes. SAE Technical Paper Series. doi:10.4271/2003-01-1110Pastor, J. V., García-Oliver, J. M., García, A., Micó, C., & Möller, S. (2016). Application of optical diagnostics to the quantification of soot in n-alkane flames under diesel conditions. Combustion and Flame, 164, 212-223. doi:10.1016/j.combustflame.2015.11.018Pastor, J., Garcia-Oliver, J. M., Garcia, A., & Nareddy, V. R. (2017). Characterization of Spray Evaporation and Mixing Using Blends of Commercial Gasoline and Diesel Fuels in Engine-Like Conditions. SAE Technical Paper Series. doi:10.4271/2017-01-0843Pastor, J. V., García-Oliver, J. M., García, A., & Pinotti, M. (2017). Effect of laser induced plasma ignition timing and location on Diesel spray combustion. Energy Conversion and Management, 133, 41-55. doi:10.1016/j.enconman.2016.11.054Pastor, J. V., García-Oliver, J. M., García, A., & Pinotti, M. (2016). Laser induced plasma methodology for ignition control in direct injection sprays. Energy Conversion and Management, 120, 144-156. doi:10.1016/j.enconman.2016.04.086Pastor, 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/ef9007328Pastor, 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.2011.05.006Reyes, M., Tinaut, F. V., Giménez, B., & Pastor, J. V. (2018). Effect of hydrogen addition on the OH* and CH* chemiluminescence emissions of premixed combustion of methane-air mixtures. International Journal of Hydrogen Energy, 43(42), 19778-19791. doi:10.1016/j.ijhydene.2018.09.005Siebers, D. L., & Higgins, B. (2001). Flame Lift-Off on Direct-Injection Diesel Sprays Under Quiescent Conditions. SAE Technical Paper Series. doi:10.4271/2001-01-0530Pastor, J. V., Garcia-Oliver, J. M., Garcia, A., & Pinotti, M. (2017). Soot Characterization of Diesel/Gasoline Blends Injected through a Single Injection System in CI engines. SAE Technical Paper Series. doi:10.4271/2017-24-0048Pastor, J. V., García, J. M., Pastor, J. M., & Buitrago, J. E. (2005). Analysis Methodology of Diesel Combustion by Using Flame Luminosity, Two-Colour Method and Laser-Induced Incandescence. SAE Technical Paper Series. doi:10.4271/2005-24-012Xuan, T., Pastor, J. V., García-Oliver, J. M., García, A., He, Z., Wang, Q., & Reyes, M. (2019). In-flame soot quantification of diesel sprays under sooting/non-sooting critical conditions in an optical engine. Applied Thermal Engineering, 149, 1-10. doi:10.1016/j.applthermaleng.2018.11.112Xuan, T., Desantes, J. M., Pastor, J. V., & Garcia-Oliver, J. M. (2019). Soot temperature characterization of spray a flames by combined extinction and radiation methodology. Combustion and Flame, 204, 290-303. doi:10.1016/j.combustflame.2019.03.023Wang, J., Yang, F., & Ouyang, M. (2015). Dieseline fueled flexible fuel compression ignition engine control based on in-cylinder pressure sensor. Applied Energy, 159, 87-96. doi:10.1016/j.apenergy.2015.08.101Han, M. (2013). The effects of synthetically designed diesel fuel properties – cetane number, aromatic content, distillation temperature, on low-temperature diesel combustion. Fuel, 109, 512-519. doi:10.1016/j.fuel.2013.03.039Benajes, J., Payri, R., Bardi, M., & Martí-Aldaraví, P. (2013). Experimental characterization of diesel ignition and lift-off length using a single-hole ECN injector. Applied Thermal Engineering, 58(1-2), 554-563. doi:10.1016/j.applthermaleng.2013.04.044Pickett, L. M., Siebers, D. L., & Idicheria, C. A. (2005). Relationship Between Ignition Processes and the Lift-Off Length of Diesel Fuel Jets. SAE Technical Paper Series. doi:10.4271/2005-01-3843Payri, R., Salvador, F. J., Manin, J., & Viera, A. (2016). Diesel ignition delay and lift-off length through different methodologies using a multi-hole injector. Applied Energy, 162, 541-550. doi:10.1016/j.apenergy.2015.10.11

An optical investigation of Fischer-Tropsch diesel and Oxymethylene dimethyl ether impact on combustion process for CI engines

[EN] Synthetic fuels (E-fuels) have shown to be an interesting alternative to replace the fossil diesel fuel due to its CO2 reduction potential as well as for their capability to diminish the soot production and therefore for improving the soot-NOX trade-off in Compression Ignition engines. Thus, the main objective of this paper was to better understand the combustion process and the in-cylinder soot formation of two of the most popular E-fuels currently: Fischer-Tropsch (FT) diesel and Oxymethylene dimethyl ether (OMEX). To achieve this aim, a single cylinder optical CI engine with a commercial piston geometry was used. Thee optical techniques (Natural Luminosity-NL, OH* chemiluminescence and 2-color pyrometry) were applied to analyze the combustion evolution and quantify the soot formation at different loads (1.5, 4.5 and 7.5 bar IMEP). OMEX presented the largest injection duration due to the low LHV. For the NL analysis, OMEX showed the lowest light intensity for the three loads tested, indicating a very low soot production. Despite of the low NL intensity, it presented the highest OH* chemiluminescence signal, indicating a higher presence of near-stoichiometric zones due to the high amount of oxygen. Regarding FT diesel, it showed a combustion behavior similar to the commercial diesel. NL, OH* and 2-color technique analysis indicated that for the three conditions tested, FT diesel presented lower soot production and a faster soot oxidation than commercial diesel.This work was partially funded by Generalitat Valenciana through the Programa Santiago Grisolia (GRISOLIAP/2018/142) program.Pastor, JV.; García Martínez, A.; Mico Reche, C.; De Vargas Lewiski, F. (2020). An optical investigation of Fischer-Tropsch diesel and Oxymethylene dimethyl ether impact on combustion process for CI engines. Applied Energy. 260:1-12. https://doi.org/10.1016/j.apenergy.2019.114238S112260Benajes, J., García, A., Monsalve-Serrano, J., & Lago Sari, R. (2018). Fuel consumption and engine-out emissions estimations of a light-duty engine running in dual-mode RCCI/CDC with different fuels and driving cycles. Energy, 157, 19-30. doi:10.1016/j.energy.2018.05.144Dronniou, N., Kashdan, J., Lecointe, B., Sauve, K., & Soleri, D. (2014). Optical Investigation of Dual-fuel CNG/Diesel Combustion Strategies to Reduce CO2 Emissions. SAE International Journal of Engines, 7(2), 873-887. doi:10.4271/2014-01-1313Tanov, S., Wang, Z., Wang, H., Richter, M., & Johansson, B. (2015). Effects of Injection Strategies on Fluid Flow and Turbulence in Partially Premixed Combustion (PPC) in a Light Duty Engine. SAE Technical Paper Series. doi:10.4271/2015-24-2455Zha, K., Busch, S., Warey, A., Peterson, R. C., & Kurtz, E. (2018). A Study of Piston Geometry Effects on Late-Stage Combustion in a Light-Duty Optical Diesel Engine Using Combustion Image Velocimetry. SAE International Journal of Engines, 11(6), 783-804. doi:10.4271/2018-01-0230Omari, A., Heuser, B., Pischinger, S., & Rüdinger, C. (2019). Potential of long-chain oxymethylene ether and oxymethylene ether-diesel blends for ultra-low emission engines. Applied Energy, 239, 1242-1249. doi:10.1016/j.apenergy.2019.02.035Hao, B., Song, C., Lv, G., Li, B., Liu, X., Wang, K., & Liu, Y. (2014). Evaluation of the reduction in carbonyl emissions from a diesel engine using Fischer–Tropsch fuel synthesized from coal. Fuel, 133, 115-122. doi:10.1016/j.fuel.2014.05.025Kook, 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.2011.10.004Rimkus, A., Žaglinskis, J., Rapalis, P., & Skačkauskas, P. (2015). Research on the combustion, energy and emission parameters of diesel fuel and a biomass-to-liquid (BTL) fuel blend in a compression-ignition engine. Energy Conversion and Management, 106, 1109-1117. doi:10.1016/j.enconman.2015.10.047Schemme, S., Samsun, R. C., Peters, R., & Stolten, D. (2017). Power-to-fuel as a key to sustainable transport systems – An analysis of diesel fuels produced from CO 2 and renewable electricity. Fuel, 205, 198-221. doi:10.1016/j.fuel.2017.05.061Lapuerta, M., Armas, O., Hernández, J. J., & Tsolakis, A. (2010). Potential for reducing emissions in a diesel engine by fuelling with conventional biodiesel and Fischer–Tropsch diesel. Fuel, 89(10), 3106-3113. doi:10.1016/j.fuel.2010.05.013Gill, S. S., Tsolakis, A., Dearn, K. D., & Rodríguez-Fernández, J. (2011). Combustion characteristics and emissions of Fischer–Tropsch diesel fuels in IC engines. Progress in Energy and Combustion Science, 37(4), 503-523. doi:10.1016/j.pecs.2010.09.001Jiao, Y., Liu, R., Zhang, Z., Yang, C., Zhou, G., Dong, S., & Liu, W. (2019). Comparison of combustion and emission characteristics of a diesel engine fueled with diesel and methanol-Fischer-Tropsch diesel-biodiesel-diesel blends at various altitudes. Fuel, 243, 52-59. doi:10.1016/j.fuel.2019.01.107Abu-Jrai, A., Tsolakis, A., Theinnoi, K., Cracknell, R., Megaritis, A., Wyszynski, M. L., & Golunski, S. E. (2006). Effect of Gas-to-Liquid Diesel Fuels on Combustion Characteristics, Engine Emissions, and Exhaust Gas Fuel Reforming. Comparative Study. Energy & Fuels, 20(6), 2377-2384. doi:10.1021/ef060332aSchaberg, P., Botha, J., Schnell, M., Hermann, H.-O., Pelz, N., & Maly, R. (2005). Emissions Performance of GTL Diesel Fuel and Blends with Optimized Engine Calibrations. SAE Technical Paper Series. doi:10.4271/2005-01-2187Iannuzzi, S. E., Barro, C., Boulouchos, K., & Burger, J. (2016). Combustion behavior and soot formation/oxidation of oxygenated fuels in a cylindrical constant volume chamber. Fuel, 167, 49-59. doi:10.1016/j.fuel.2015.11.060Pellegrini, L., Marchionna, M., Patrini, R., Beatrice, C., Del Giacomo, N., & Guido, C. (2012). Combustion Behaviour and Emission Performance of Neat and Blended Polyoxymethylene Dimethyl Ethers in a Light-Duty Diesel Engine. SAE Technical Paper Series. doi:10.4271/2012-01-1053Zhu, R., Wang, X., Miao, H., Huang, Z., Gao, J., & Jiang, D. (2008). Performance and Emission Characteristics of Diesel Engines Fueled with Diesel−Dimethoxymethane (DMM) Blends. Energy & Fuels, 23(1), 286-293. doi:10.1021/ef8005228Härtl, M., Seidenspinner, P., Jacob, E., & Wachtmeister, G. (2015). Oxygenate screening on a heavy-duty diesel engine and emission characteristics of highly oxygenated oxymethylene ether fuelOME1. Fuel, 153, 328-335. doi:10.1016/j.fuel.2015.03.012Omari, A., Heuser, B., & Pischinger, S. (2017). Potential of oxymethylenether-diesel blends for ultra-low emission engines. Fuel, 209, 232-237. doi:10.1016/j.fuel.2017.07.107Ma, X., Ma, Y., Sun, S., Shuai, S.-J., Wang, Z., & Wang, J.-X. (2017). PLII-LEM and OH* Chemiluminescence Study on Soot Formation in Spray Combustion of PODEn-Diesel Blend Fuels in a Constant Volume Vessel. SAE Technical Paper Series. doi:10.4271/2017-01-2329Liu, H., Wang, Z., Zhang, J., Wang, J., & Shuai, S. (2017). Study on combustion and emission characteristics of Polyoxymethylene Dimethyl Ethers/diesel blends in light-duty and heavy-duty diesel engines. Applied Energy, 185, 1393-1402. doi:10.1016/j.apenergy.2015.10.183Lumpp, B., Rothe, D., Pastötter, C., Lämmermann, R., & Jacob, E. (2011). OXYMETHYLENE ETHERS AS DIESEL FUEL ADDITIVES OF THE FUTURE. MTZ worldwide, 72(3), 34-38. doi:10.1365/s38313-011-0027-zLiu, H., Wang, Z., Wang, J., & He, X. (2016). Improvement of emission characteristics and thermal efficiency in diesel engines by fueling gasoline/diesel/PODEn blends. Energy, 97, 105-112. doi:10.1016/j.energy.2015.12.110Chen, H., Su, X., Li, J., & Zhong, X. (2019). Effects of gasoline and polyoxymethylene dimethyl ethers blending in diesel on the combustion and emission of a common rail diesel engine. Energy, 171, 981-999. doi:10.1016/j.energy.2019.01.089Payri, R., De La Morena, J., Monsalve-Serrano, J., Pesce, F. C., & Vassallo, A. (2018). Impact of counter-bore nozzle on the combustion process and exhaust emissions for light-duty diesel engine application. International Journal of Engine Research, 20(1), 46-57. doi:10.1177/1468087418819250De Simio, L., & Iannaccone, S. (2019). Gaseous and particle emissions in low-temperature combustion diesel–HCNG dual-fuel operation with double pilot injection. Applied Energy, 253, 113602. doi:10.1016/j.apenergy.2019.113602Denny, M., Holst, F., Helmantel, A., Persson, H., Tunestål, P., & Andersson, Ö. (2019). Impact of closely-coupled triple-pilot and conventional double-pilot injection strategies in a LD diesel engine. Fuel, 246, 141-148. doi:10.1016/j.fuel.2019.02.101Pastor, J. V., García-Oliver, J. M., García, A., & Pinotti, M. (2016). Laser induced plasma methodology for ignition control in direct injection sprays. Energy Conversion and Management, 120, 144-156. doi:10.1016/j.enconman.2016.04.086Jakob, M., Hülser, T., Janssen, A., Adomeit, P., Pischinger, S., & Grünefeld, G. (2012). Simultaneous high-speed visualization of soot luminosity and OH∗ chemiluminescence of alternative-fuel combustion in a HSDI diesel engine under realistic operating conditions. Combustion and Flame, 159(7), 2516-2529. doi:10.1016/j.combustflame.2012.03.004Pastor, J. V., García-Oliver, J. M., García, A., Micó, C., & Möller, S. (2016). Application of optical diagnostics to the quantification of soot in n-alkane flames under diesel conditions. Combustion and Flame, 164, 212-223. doi:10.1016/j.combustflame.2015.11.018Xuan, T., Pastor, J. V., García-Oliver, J. M., García, A., He, Z., Wang, Q., & Reyes, M. (2019). In-flame soot quantification of diesel sprays under sooting/non-sooting critical conditions in an optical engine. Applied Thermal Engineering, 149, 1-10. doi:10.1016/j.applthermaleng.2018.11.112Payri, F., Molina, S., Martín, J., & Armas, O. (2006). Influence of measurement errors and estimated parameters on combustion diagnosis. Applied Thermal Engineering, 26(2-3), 226-236. doi:10.1016/j.applthermaleng.2005.05.006Payri, F., Olmeda, P., Martín, J., & García, A. (2011). A complete 0D thermodynamic predictive model for direct injection diesel engines. Applied Energy, 88(12), 4632-4641. doi:10.1016/j.apenergy.2011.06.005Pastor, J., Olmeda, P., Martín, J., & Lewiski, F. (2018). Methodology for Optical Engine Characterization by Means of the Combination of Experimental and Modeling Techniques. Applied Sciences, 8(12), 2571. doi:10.3390/app812257

Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles

Lipid and polymer stabilized microbubbles are used in medicine as contrast agents for ultrasound imaging and are being developed for the delivery of water soluble drugs to diseased areas of the body. However, many new therapeutics exhibit poor water solubility or stability, which has led to the requirement for the development of effective hydrophobic drug delivery systems. This study presents a new method to produce microbubbles coated with an oil layer capable of encapsulating hydrophobic drugs and suitable for targeted, triggered drug release. This new method utilizes highly controllable flow-focusing microfluidics with lipid oil nanodroplets self-assembling and spreading at gas–aqueous interfaces. Oil layer inside microbubbles were produced with diameters of 2.4±0.3 μm (s.d., 1.6 μm) and at concentrations up to 106 bubbles per milliliter. The mechanism of oil layer inside microbubble assembly and stability were characterized using methods including contact angle measurements, quartz crystal microbalance with dissipation monitoring and fluorescence resonance energy transfer imaging

Experimental Study of the Effect of Hydrotreated Vegetable Oil and Oxymethylene Ethers on Main Spray and Combustion Characteristics under Engine Combustion Network Spray A Conditions

[EN] Featured Application This work contributes to the understanding of the macroscopic characteristics of the spray as well as to the evolution of the combustion process for alternative fuels. All these fuels have been studied under the same operating conditions than diesel therefore the comparison can be made directly, leaving in evidence that some fuels can achieve a similar behavior to diesel in terms of auto ignition but avoiding one of the biggest disadvantages of diesel such as the soot formation. Moreover, the quantification of characteristic parameters such as ignition delay, liquid length, vapor penetration and flame lift-off length represent the most important data to adjust and subsequently validate the computational models that simulate the spray evolution and combustion development of these alternative fuels inside the combustion chamber. The stringent emission regulations have motivated the development of cleaner fuels as diesel surrogates. However, their different physical-chemical properties make the study of their behavior in compression ignition engines essential. In this sense, optical techniques are a very effective tool for determining the spray evolution and combustion characteristics occurring in the combustion chamber. In this work, quantitative parameters describing the evolution of diesel-like sprays such as liquid length, spray penetration, ignition delay, lift-off length and flame penetration as well as the soot formation were tested in a constant high pressure and high temperature installation using schlieren, OH* chemiluminescence and diffused back-illumination extinction imaging techniques. Boundary conditions such as rail pressure, chamber density and temperature were defined using guidelines from the Engine Combustion Network (ECN). Two paraffinic fuels (dodecane and a renewable hydrotreated vegetable oil (HVO)) and two oxygenated fuels (methylal identified as OME(1)and a blend of oxymethylene ethers, identified as OMEx) were tested and compared to a conventional diesel fuel used as reference. Results showed that paraffinic fuels and OME(x)sprays have similar behavior in terms of global combustion metrics. In the case of OME1, a shorter liquid length, but longer ignition delay time and flame lift-off length were observed. However, in terms of soot formation, a big difference between paraffinic and oxygenated fuels could be appreciated. While paraffinic fuels did not show any significant decrease of soot formation when compared to diesel fuel, soot formed by OME(1)and OME(x)was below the detection threshold in all tested conditions.This research has been partly funded by the European Union's Horizon 2020 Programme through the ENERXICO project, grant agreement no 828947, and from the Mexican Department of Energy, CONACYT-SENER Hidrocarburos grant agreement no B-S-69926 and by Universitat Politecnica de Valencia through the Programa de Ayudas de Investigacion y Desarrollo (PAID-01-18).Pastor, JV.; García-Oliver, JM.; Mico Reche, C.; Garcia-Carrero, AA.; Gómez, A. (2020). Experimental Study of the Effect of Hydrotreated Vegetable Oil and Oxymethylene Ethers on Main Spray and Combustion Characteristics under Engine Combustion Network Spray A Conditions. Applied Sciences. 10(16):1-20. https://doi.org/10.3390/app10165460S1201016Reşitoğlu, İ. A., Altinişik, K., & Keskin, A. (2014). The pollutant emissions from diesel-engine vehicles and exhaust aftertreatment systems. Clean Technologies and Environmental Policy, 17(1), 15-27. doi:10.1007/s10098-014-0793-9Mohan, B., Yang, W., & Chou, S. kiang. (2013). Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—A review. Renewable and Sustainable Energy Reviews, 28, 664-676. doi:10.1016/j.rser.2013.08.051Leach, F., Kalghatgi, G., Stone, R., & Miles, P. (2020). The scope for improving the efficiency and environmental impact of internal combustion engines. Transportation Engineering, 1, 100005. doi:10.1016/j.treng.2020.100005Kim, H., Ge, J., & Choi, N. (2018). Application of Palm Oil Biodiesel Blends under Idle Operating Conditions in a Common-Rail Direct-Injection Diesel Engine. Applied Sciences, 8(12), 2665. doi:10.3390/app8122665Tziourtzioumis, D., & Stamatelos, A. (2017). Experimental Investigation of the Effect of Biodiesel Blends on a DI Diesel Engine’s Injection and Combustion. Energies, 10(7), 970. doi:10.3390/en10070970Merola, S. S., Tornatore, C., Iannuzzi, S. E., Marchitto, L., & Valentino, G. (2014). Combustion process investigation in a high speed diesel engine fuelled with n-butanol diesel blend by conventional methods and optical diagnostics. Renewable Energy, 64, 225-237. doi:10.1016/j.renene.2013.11.017Choi, K., Park, S., Roh, H. G., & Lee, C. S. (2019). Combustion and Emission Reduction Characteristics of GTL-Biodiesel Fuel in a Single-Cylinder Diesel Engine. Energies, 12(11), 2201. doi:10.3390/en12112201Dimitriadis, A., Seljak, T., Vihar, R., Žvar Baškovič, U., Dimaratos, A., Bezergianni, S., … Katrašnik, T. (2020). Improving PM-NOx trade-off with paraffinic fuels: A study towards diesel engine optimization with HVO. Fuel, 265, 116921. doi:10.1016/j.fuel.2019.116921Pastor, J. V., García, A., Micó, C., & Lewiski, F. (2020). An optical investigation of Fischer-Tropsch diesel and Oxymethylene dimethyl ether impact on combustion process for CI engines. Applied Energy, 260, 114238. doi:10.1016/j.apenergy.2019.114238Bergthorson, J. M., & Thomson, M. J. (2015). A review of the combustion and emissions properties of advanced transportation biofuels and their impact on existing and future engines. Renewable and Sustainable Energy Reviews, 42, 1393-1417. doi:10.1016/j.rser.2014.10.034Yehliu, K., Boehman, A. L., & Armas, O. (2010). Emissions from different alternative diesel fuels operating with single and split fuel injection. Fuel, 89(2), 423-437. doi:10.1016/j.fuel.2009.08.025Gómez, A., Soriano, J. A., & Armas, O. (2016). Evaluation of sooting tendency of different oxygenated and paraffinic fuels blended with diesel fuel. Fuel, 184, 536-543. doi:10.1016/j.fuel.2016.07.049Benajes, J., García, A., Monsalve-Serrano, J., & Martínez-Boggio, S. (2020). Potential of using OMEx as substitute of diesel in the dual-fuel combustion mode to reduce the global CO2 emissions. Transportation Engineering, 1, 100001. doi:10.1016/j.treng.2020.01.001Burger, J., Siegert, M., Ströfer, E., & Hasse, H. (2010). Poly(oxymethylene) dimethyl ethers as components of tailored diesel fuel: Properties, synthesis and purification concepts. Fuel, 89(11), 3315-3319. doi:10.1016/j.fuel.2010.05.014Iannuzzi, S. E., Barro, C., Boulouchos, K., & Burger, J. (2017). POMDME-diesel blends: Evaluation of performance and exhaust emissions in a single cylinder heavy-duty diesel engine. Fuel, 203, 57-67. doi:10.1016/j.fuel.2017.04.089Omari, A., Heuser, B., & Pischinger, S. (2017). Potential of oxymethylenether-diesel blends for ultra-low emission engines. Fuel, 209, 232-237. doi:10.1016/j.fuel.2017.07.107Bjørgen, K. O. P., Emberson, D. R., & Løvås, T. (2020). Combustion and soot characteristics of hydrotreated vegetable oil compression-ignited spray flames. Fuel, 266, 116942. doi:10.1016/j.fuel.2019.116942Marchitto, L., Merola, S. S., Tornatore, C., & Valentino, G. (2016). An Experimental Investigation of Alcohol/Diesel Fuel Blends on Combustion and Emissions in a Single-Cylinder Compression Ignition Engine. SAE Technical Paper Series. doi:10.4271/2016-01-0738Payri, R., Gimeno, J., Bardi, M., & Plazas, A. H. (2013). Study liquid length penetration results obtained with a direct acting piezo electric injector. Applied Energy, 106, 152-162. doi:10.1016/j.apenergy.2013.01.027Benajes, J., Payri, R., Bardi, M., & Martí-Aldaraví, P. (2013). Experimental characterization of diesel ignition and lift-off length using a single-hole ECN injector. Applied Thermal Engineering, 58(1-2), 554-563. doi:10.1016/j.applthermaleng.2013.04.044Xuan, T., Desantes, J. M., Pastor, J. V., & Garcia-Oliver, J. M. (2019). Soot temperature characterization of spray a flames by combined extinction and radiation methodology. Combustion and Flame, 204, 290-303. doi:10.1016/j.combustflame.2019.03.023Pastor, J. V., Payri, R., Garcia-Oliver, J. M., & Briceño, F. J. (2013). Schlieren Methodology for the Analysis of Transient Diesel Flame Evolution. SAE International Journal of Engines, 6(3), 1661-1676. doi:10.4271/2013-24-0041Pastor, J. V., García, A., Micó, C., & García-Carrero, A. A. (2020). Experimental study of influence of Liquefied Petroleum Gas addition in Hydrotreated Vegetable Oil fuel on ignition delay, flame lift off length and soot emission under diesel-like conditions. Fuel, 260, 116377. doi:10.1016/j.fuel.2019.116377Reyes, M., Tinaut, F. V., Giménez, B., & Pastor, J. V. (2018). Effect of hydrogen addition on the OH* and CH* chemiluminescence emissions of premixed combustion of methane-air mixtures. International Journal of Hydrogen Energy, 43(42), 19778-19791. doi:10.1016/j.ijhydene.2018.09.005Xuan, T., Pastor, J. V., García-Oliver, J. M., García, A., He, Z., Wang, Q., & Reyes, M. (2019). In-flame soot quantification of diesel sprays under sooting/non-sooting critical conditions in an optical engine. Applied Thermal Engineering, 149, 1-10. doi:10.1016/j.applthermaleng.2018.11.112Choi, M. Y., Mulholland, G. W., Hamins, A., & Kashiwagi, T. (1995). Comparisons of the soot volume fraction using gravimetric and light extinction techniques. Combustion and Flame, 102(1-2), 161-169. doi:10.1016/0010-2180(94)00282-wLi, D., He, Z., Xuan, T., Zhong, W., Cao, J., Wang, Q., & Wang, P. (2017). Simultaneous capture of liquid length of spray and flame lift-off length for second-generation biodiesel/diesel blended fuel in a constant volume combustion chamber. Fuel, 189, 260-269. doi:10.1016/j.fuel.2016.10.058Lequien, G., Berrocal, E., Gallo, Y., Themudo e Mello, A., Andersson, O., & Johansson, B. (2013). Effect of Jet-Jet Interactions on the Liquid Fuel Penetration in an Optical Heavy-Duty DI Diesel Engine. SAE Technical Paper Series. doi:10.4271/2013-01-1615Kook, 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.2011.10.004Payri, R., Salvador, F. J., Manin, J., & Viera, A. (2016). Diesel ignition delay and lift-off length through different methodologies using a multi-hole injector. Applied Energy, 162, 541-550. doi:10.1016/j.apenergy.2015.10.118Pickett, L. M., & Siebers, D. L. (2005). Orifice Diameter Effects on Diesel Fuel Jet Flame Structure. Journal of Engineering for Gas Turbines and Power, 127(1), 187-196. doi:10.1115/1.1760525Pastor, J. V., García-Oliver, J. M., López, J. J., & Vera-Tudela, W. (2016). An experimental study of the effects of fuel properties on reactive spray evolution using Primary Reference Fuels. Fuel, 163, 260-270. doi:10.1016/j.fuel.2015.09.064Pickett, L. M., & Siebers, D. L. (2004). Non-Sooting, Low Flame Temperature Mixing-Controlled DI Diesel Combustion. SAE Technical Paper Series. doi:10.4271/2004-01-1399Aatola, H., Larmi, M., Sarjovaara, T., & Mikkonen, S. (2008). Hydrotreated Vegetable Oil (HVO) as a Renewable Diesel Fuel: Trade-off between NOx, Particulate Emission, and Fuel Consumption of a Heavy Duty Engine. SAE International Journal of Engines, 1(1), 1251-1262. doi:10.4271/2008-01-2500Marinov, N. M., Pitz, W. J., Westbrook, C. K., Vincitore, A. M., Castaldi, M. J., Senkan, S. M., & Melius, C. F. (1998). Aromatic and Polycyclic Aromatic Hydrocarbon Formation in a Laminar Premixed n-Butane Flame. Combustion and Flame, 114(1-2), 192-213. doi:10.1016/s0010-2180(97)00275-

Changes in glial cell phenotypes precede overt neurofibrillary tangle formation, correlate with markers of cortical cell damage, and predict cognitive status of individuals at Braak III-IV stages

Clinico-pathological correlation studies show that some otherwise healthy elderly individuals who never developed cognitive impairment harbor a burden of Alzheimer’s disease lesions (plaques and tangles) that would be expected to result in dementia. In the absence of comorbidities explaining such discrepancies, there is a need to identify other brain changes that meaningfully contribute to the cognitive status of an individual in the face of such burdens of plaques and tangles. Glial inflammatory responses, a universal phenomenon in symptomatic AD, show robust association with degree of cognitive impairment, but their significance in early tau pathology stages and contribution to the trajectory of cognitive decline at an individual level remain widely unexplored. We studied 55 brains from individuals at intermediate stages of tau tangle pathology (Braak III-IV) with diverging antemortem cognition (demented vs. non-demented, here termed `resilient’), and age-matched cognitively normal controls (Braak 0-II). We conducted quantitative assessments of amyloid and tau lesions, cellular vulnerability markers, and glial phenotypes in temporal pole (Braak III-IV region) and visual cortex (Braak V-VI region) using artificial-intelligence based semiautomated quantifications. We found distinct glial responses with increased proinflammatory and decreased homeostatic markers, both in regions with tau tangles (temporal pole) and without overt tau deposits (visual cortex) in demented but not in resilient. These changes were significantly associated with markers of cortical cell damage. Similar phenotypic glial changes were detected in the white matter of demented but not resilient and were associated with higher burden of overlying cortical cellular damage in regions with and without tangles. Our data suggest that changes in glial phenotypes in cortical and subcortical regions represent an early phenomenon that precedes overt tau deposition and likely contributes to cell damage and loss of brain function predicting the cognitive status of individuals at intermediate stages of tau aggregate burden (Braak III-IV)

Quantum Principal Bundles and Corresponding Gauge Theories

A generalization of classical gauge theory is presented, in the framework of a noncommutative-geometric formalism of quantum principal bundles over smooth manifolds. Quantum counterparts of classical gauge bundles, and classical gauge transformations, are introduced and investigated. A natural differential calculus on quantum gauge bundles is constructed and analyzed. Kinematical and dynamical properties of corresponding gauge theories are discussed.Comment: 28 pages, AMS-LaTe

Evaluation of Lipid-Stabilised Tripropionin Nanodroplets as a Delivery Route for Combretastatin A4

Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and preparation conditions on the size of the nanoemulsion nanodroplets for food applications, analogous studies for nanoemulsions for therapeutic applications are limited. Here we present a study on the production of lipid-stabilised oil nanodroplets (LONDs) towards medical applications. A number of biocompatible oils were used to form LONDs with phospholipid coatings, and among these, squalane and tripropionin were chosen as model oils for subsequent studies. LONDs were formed by high pressure homogenisation, and their size was found to decrease with increasing production pressure. When produced at 175 MPa, all LONDs samples exhibited sizes between 100 − 300 nm, with polydispersity index PI between 0.1 − 0.3. The LONDs were stable for over six weeks, at 4 °C, and also under physiological conditions, showing modest changes in size (<10%). The hydrophobic drug combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency of approximately 76%, achieving drug concentration of approximately 1.3 mg/ml. SVR mouse endothelial cells treated with CA4 tripropionin LONDs showed the microtubule disruption, characteristic of drug uptake for all tested doses, which suggests successful release of the CA4 from the LONDs

Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology

Microglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer’s disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau pathology is more prominent than amyloid-beta pathology, a microglial degenerative process has been reported. In this work, we have directly compared the microglial response in two different transgenic tau mouse models: ThyTau22 and P301S. Surprisingly, these two models showed important differences in the microglial profile and tau pathology. Where ThyTau22 hippocampus manifested mild microglial activation, P301S mice exhibited a strong microglial response in parallel with high phospho-tau accumulation. This differential phospho-tau expression could account for the different microglial response in these two tau strains. However, soluble (S1) fractions from ThyTau22 hippocampus presented relatively high content of soluble phospho-tau (AT8-positive) and were highly toxic for microglial cells in vitro, whereas the correspondent S1 fractions from P301S mice displayed low soluble phospho-tau levels and were not toxic for microglial cells. Therefore, not only the expression levels but the aggregation of phospho-tau should differ between both models. In fact, most of tau forms in the P301S mice were aggregated and, in consequence, forming insoluble tau species. We conclude that different factors as tau mutations, accumulation, phosphorylation, and/or aggregation could account for the distinct microglial responses observed in these two tau models. For this reason, deciphering the molecular nature of toxic tau species for microglial cells might be a promising therapeutic approach in order to restore the deficient immunological protection observed in AD hippocampus

Plaque-Associated Oligomeric Amyloid-Beta Drives Early Synaptotoxicity in APP/PS1 Mice Hippocampus: Ultrastructural Pathology Analysis

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. In this sense, synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease. At the histopathological level, post mortem AD brains typically exhibit intraneuronal neurofibrillary tangles (NFTs) along with the accumulation of amyloid-beta (Abeta) peptides in the form of extracellular deposits. Specifically, the oligomeric soluble forms of Abeta are considered the most synaptotoxic species. In addition, neuritic plaques are Abeta deposits surrounded by activated microglia and astroglia cells together with abnormal swellings of neuronal processes named dystrophic neurites. These periplaque aberrant neurites are mostly presynaptic elements and represent the first pathological indicator of synaptic dysfunction. In terms of losing synaptic proteins, the hippocampus is one of the brain regions most affected in AD patients. In this work, we report an early decline in spatial memory, along with hippocampal synaptic changes, in an amyloidogenic APP/PS1 transgenic model. Quantitative electron microscopy revealed a spatial synaptotoxic pattern around neuritic plaques with significant loss of periplaque synaptic terminals, showing rising synapse loss close to the border, especially in larger plaques. Moreover, dystrophic presynapses were filled with autophagic vesicles in detriment of the presynaptic vesicular density, probably interfering with synaptic function at very early synaptopathological disease stages. Electron immunogold labeling showed that the periphery of amyloid plaques, and the associated dystrophic neurites, was enriched in Abeta oligomers supporting an extracellular location of the synaptotoxins. Finally, the incubation of primary neurons with soluble fractions derived from 6-month-old APP/PS1 hippocampus induced significant loss of synaptic proteins, but not neuronal death. Indeed, this preclinical transgenic model could serve to investigate therapies targeted at initial stages of synaptic dysfunction relevant to the prodromal and early AD.This study was supported by the Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by the FEDER funds from European Union, through grants PI18/01557 (to AG) and PI18/01556 (to JV); by the Junta de Andalucia Consejería de Economía y Conocimiento through grants UMA18-FEDERJA-211 (to AG), P18-RT-2233 (to AG), and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014–2020; by the Spanish Minister of Science and Innovation grant PID2019-108911RA-100 (to DB-V), Beatriz Galindo program BAGAL18/00052 (to DB-V) grant PID2019-107090RA-I00 (to IM-G), and Ramon y Cajal Program RYC-2017-21879 (to IM-G); and by the Malaga University grants B1-2019_07 (to ES-M) and B1-2019_06 (to IM-G). MM-O held a predoctoral contract from Malaga University and ES-M a postdoctoral contract (DOC_00251) from Junta de Andalucia