Cervical artery dissection: An atypical presentation with Ehlers-Danlos-like collagen pathology?

The authors took skin biopsies of the macroscopically normal skin of seven consecutive patients with spontaneous cervical artery dissection (SCAD). Histologically, alterations of the collagen and elastic fiber networks were found in six patients. In five, the histologic, immunohistochemical, and ultrastructural changes were similar to those usually found in Ehlers-Danlos syndrome (EDS). This suggests that SCAD is frequently associated with the dermal alterations seen in EDS

Vital and functional outcomes of the first-ever hemispheric stroke, epidemiological comparative study between Kunming (China) and Limoges (France)

AbstractBackgroundClinical outcomes and socioeconomic consequences after a stroke may differ between regions.MethodsOne cohort was established prospectively in Kunming (China) to compare with a cohort of 156 stroke patients included in Limoges (France). During 1 year, patients hospitalized within 48hours for a first-ever hemispheric stroke were included. Demographic data and neurocardiovascular risk factors were registered. Hemiplegia was evaluated. Functional outcome was assessed using the Barthel Index (BI) after 3 months.ResultsOne hundred and eighteen patients were included in Kunming. Patients of Kunming were younger (61.4±13.4 vs 72.3±14.6 years in Limoges, P<0.0001), more involved in professional activity (36.4% vs 12.8%, P<0.0001). Survival analysis indicated that mortality did not differ between cohorts, but independently predicted by coma at the 2nd day (HR=9.33, 95% CI [4.39, 19.78]) and age>70 years (HR=6.29, 95% CI [2.36, 16.59]). Despite a better baseline BI for patients of Kunming (50.0±34.9 vs 37.4±34.2, P=0.0031), after adjustment for confusing, patients in Limoges had a 2.11 OR 95% CI [1.03, 4.31]) to reach a BI>80 at 3 months.ConclusionsFunctional recovery for patients of Kunming was not as good as expected. The socioeconomic consequences of stroke in Kunming are significant as they involved younger subjects who were still in work

Comparison of different techniques for characterizing the diesel injector internal dimensions

[EN] The geometry of certain parts of diesel injectors is key to the injection, atomization and fuel-air mixing phenomena. Small variations on the geometrical parameters may have a strong influence on the aforementioned processes. Thus, OEMs need to assess their manufacturing tolerances, whereas researchers in the field (both experimentalists and modelers) rely on the accuracy of a certain metrology technique for their studies. In the current paper, an investigation of the capability of different experimental techniques to determine the geometry of a modern diesel fuel injector has been performed. For this purpose, three main elements of the injector have been evaluated: the control volume inlet and outlet orifices, together with the nozzle orifices. While the direct observation of the samples through an optical microscope is only possible for the simplest pieces, both Computed Tomography Scanning and the visualization of silicone molds technique have proven their ability to characterize the most complex internal shapes corresponding to the internal injector elements. Indeed, results indicate that the differences observed among these methodologies for the determination of the control volume inlet orifice diameter and the nozzle orifice dimensions are smaller than the uncertainties related to the experimental techniques, showing that they are both equally accurate. This implies that the choice of a given technique for the particular application of determining the geometry of diesel injectors can be done on the basis of availability, intrusion and costs, rather than on its accuracy.This work was partly sponsored by "Ministerio de Economia y Competitividad", of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor", Reference TRA2015-67679-c2-1-R.Salvador, FJ.; Gimeno, J.; De La Morena, J.; Carreres, M. (2018). Comparison of different techniques for characterizing the diesel injector internal dimensions. Experimental Techniques. 42(5):467-472. https://doi.org/10.1007/s40799-018-0246-1S467472425Mobasheri R, Peng Z, Mostafa S (2012) Analysis the effect of advanced injection strategies on engine performance and pollutant emissions in a heavy duty DI-diesel engine by CFD modeling. Int J Heat Fluid Flow 33(1):59–69Dhar A, Agarwal AK (2015) Experimental investigations of the effect of pilot injection on performance, emissions and combustion characteristics of Karanja biodiesel fuelled CRDI engine. Energy Convers Manag 93:357–366Mohan B, Yang W, Chou SK (2013) Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—a review. Renew Sust Energ Rev 28(x):664–676Petrovic V, Bracanovic Z, Grozdanic B, Petrovic S, Sazhin S, Knezevic D (2015) The design of a full flow dilution tunnel with a critical flow venturi for the measurement of diesel engine particulate emission. FME Trans 43(2):99–106Ilić Z, Rasuo B, Jovanović M, Janković D (2013) Impact of changing quality of air/fuel mixture during flight of a piston engine aircraft with respect to vibration low frequency spectrum. FME Trans 41(1):25–32Luján JM, Tormos B, Salvador FJ, Galgar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: Preliminaru study I. Biomass & Bioenergy 33(6–7):941–947Postrioti L, Mariani F, Battistoni M (2012) Experimental and numerical momentum flux evaluation of high pressure diesel spray. Fuel 98:149–163Payri R, Salvador FJ, Gimeno J, Venegas O (2016) A technique to match the refractive index of different diesel fuels with the refractive index of transparent materials to improve the experimental visualization. Exp Tech 40(1):261–269Duran SP, Porter JM, Parker TE (2015) Ballistic imaging of diesel sprays using a picosecond laser: characterization and demonstration. Appl Opt 54(7):1743Payri R, Salvador FJ, Gimeno J et al (2011) Flow regime effects on non-cavitating injection nozzles over spray behavior. Int J Heat Fluid Flow 32(1):273–284Koukouvinis P, Gavaises M, Li J, Wang L (2016) Large Eddy simulation of diesel injector including cavitation effects and correlation to erosion damage. Fuel 175:26–39Som S, Aggarwal SK (2010) Effects of primary breakup modeling on spray and combustion characteristics of compression ignition engines. Combust Flame 157(6):1179–1193Salvador FJ, De la Morena J, Martínez-López J, Jaramillo D (2017) Assessment of compressibility effects on internal nozzle flow in diesel injectors at very high injection pressures. Energy Convers Manag 132:221–230Salvador FJ, Gimeno J, de la Morena J, Martí-Aldaraví P (2012) Using one-dimensional modelling to analyze the influence of the use of biodiesels on the dynamic behaviour of solenoid-operated injectors in common rail systems: Results of the simulation and discussion. Energy Convers Manag 54(1):122–132Taghavifar H, Khalilarya S, Jafarmadar S, Baghery F (2016) 3-D numerical consideration of nozzle structure on combustion and emission characteristics of DI diesel injector. Appl Math Model 40(19–20):8630–8646Edelbauer W (2017) Numerical simulation of cavitating injector flow and liquid spray break-up by combination of Eulerian–Eulerian and volume-of-fluid methods. Comput Fluids 144:19–33Salvador FJ, Carreres M, Jaramillo D, Martínez-López J (2015) Comparison of microsac and VCO diesel injector nozzles in terms of internal nozzle flow characteristics. Energy Convers Manag 103:284–299Salvador FJ, Martínez-López J, Romero JV, Roselló MD (2013) Study of the influence of the needle eccentricity on the internal flow in diesel injector nozzles by computational fluid dynamics calculations. Int J Comput Math 91, no. June:24–31Payri R, Salvador FJ, Carreres M, De la Morena J (Apr. 2016) Fuel temperature influence on the performance of a last generation common-rail diesel ballistic injector. Part II: 1D model development, validation and analysis. Energy Convers Manag 114:376–391Salvador FJ, Hoyas S, Novella R, Martinez-López J (2011) Numerical simulation and extended validation of two-phase compressible flow in diesel injector nozzles. Proc Inst Mech Eng Part-D-J Automob Eng 225(D4):545–563Satkoski C, Shaver G (2011) Piezoelectric fuel injection: pulse-to-pulse coupling and flow rate estimation. IEEE/ASME Trans Mechatron 16(4):627–642Ferrari A, Mittica A (2016) Response of different injector typologies to dwell time variations and a hydraulic analysis of closely-coupled and continuous rate shaping injection schedules. Appl Energy 169:899–911Payri R, Salvador FJ, Gimeno J, De la Morena J (2011) Analysis of diesel spray atomization by means of a near-nozzle field visualization technique. At Sprays 21(9):753–774Li T, Moon S, Sato K, Yokohata H (Feb. 2017) A comprehensive study on the factors affecting near-nozzle spray dynamics of multi-hole GDI injectors. Fuel 190:292–302Yu W, Yang W, Zhao F (2017) Investigation of internal nozzle flow, spray and combustion characteristics fueled with diesel, gasoline and wide distillation fuel (WDF) based on a piezoelectric injector and a direct injection compression ignition engine. Appl Therm Eng 114:905–920Salvador FJ, Carreres M, Crialesi-Esposito M, Plazas AH (2017) Determination of critical operating and geometrical parameters in diesel injectors through one dimensional modelling, design of experiments and an analysis of variance. Proc Inst Mech Eng Part D J Automob EngMacian V, Bermúdez V, Payri R, Gimeno J (2003) New technique for determination of internal geometry of a diesel nozzle with the use of silicone methodology. Exp Tech 27, no April:39–43Piano A, Millo F, Postrioti L, Biscontini G, Cavicchi A, and Pesce FC, (2016) “Numerical and experimental assessment of a solenoid common-rail injector operation with advanced injection strategies,” SAE Int J Engines 9(1)Mitroglou N, Lorenzi M, Santini M, Gavaises M (2016) Application of X-ray micro-computed tomography on high-speed cavitating diesel fuel flows. Exp Fluids 57(11):1–14Kastengren AL, Tilocco FZ, Powell CF, Manin J, Pickett LM, Payri R, Bazyn T (2012) Engine combustion network (ECN): measurements of nozzle geometry and hydraulic behavior. At Sprays 22(12):1011–1052Otsu N (1979) A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 9(1):62–6

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Sildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor, has been proposed as a treatment for pulmonary arterial hypertension (PAH). The mechanism of its anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC) is unclear. Nuclear translocation of nuclear factor of activated T-cells (NFAT) is thought to be involved in PASMC proliferation and PAH. Increase in cytosolic free [Ca²⁺] ([Ca²⁺]_i) is a prerequisite for NFAT nuclear translocation. Elevated [Ca²⁺]_iin PASMC of PAH patients has been demonstrated through up-regulation of store-operated Ca²⁺channels (SOC) which is encoded by the transient receptor potential (TRP) channel protein. Thus we investigated if: 1) up-regulation of TRPC1 channel expression which induces enhancement of SOC-mediated Ca²⁺influx and increase in [Ca²⁺]_iis involved in hypoxia-induced PASMC proliferation; 2) hypoxia-induced promotion of [Ca²⁺]_ileads to nuclear translocation of NFAT and regulates PASMC proliferation and TRPC1 expression; 3) the anti-proliferative effect of sildenafil is mediated by inhibition of this SOC/Ca²⁺/NFAT pathway.</p> <p>Methods</p> <p>Human PASMC were cultured under hypoxia (3% O₂) with or without sildenafil treatment for 72 h. Cell number and cell viability were determined with a hemocytometer and MTT assay respectively. [Ca²⁺]_iwas measured with a dynamic digital Ca²⁺imaging system by loading PASMC with fura 2-AM. TRPC1 mRNA and protein level were detected by RT-PCR and Western blotting respectively. Nuclear translocation of NFAT was determined by immunofluoresence microscopy.</p> <p>Results</p> <p>Hypoxia induced PASMC proliferation with increases in basal [Ca²⁺]_iand Ca²⁺entry via SOC (SOCE). These were accompanied by up-regulation of TRPC1 gene and protein expression in PASMC. NFAT nuclear translocation was significantly enhanced by hypoxia, which was dependent on SOCE and sensitive to SOC inhibitor SKF96365 (SKF), as well as cGMP analogue, 8-brom-cGMP. Hypoxia-induced PASMC proliferation and TRPC1 up-regulation were inhibited by SKF and NFAT blocker (VIVIT and Cyclosporin A). Sildenafil treatment ameliorated hypoxia-induced PASMC proliferation and attenuated hypoxia-induced enhancement of basal [Ca²⁺]_i, SOCE, up-regulation of TRPC1 expression, and NFAT nuclear translocation.</p> <p>Conclusion</p> <p>The SOC/Ca²⁺/NFAT pathway is, at least in part, a downstream mediator for the anti-proliferative effect of sildenafil, and may have therapeutic potential for PAH treatment.</p

Computational investigation of diesel nozzle internal flow during the complete injection event

[EN] Currently, diesel engines are calibrated using more and more complex multiple injection strategies. Under these conditions, the characteristics of the flow exiting the fuel injector are strongly affected by the transient interaction between the needle, the sac volume and the orifices, which are not yet clear. In the current paper, a methodology combining a 1D injector model and 3D-CFD simulations is proposed. First, the characteristics of the nozzle flow have been experimentally assessed in transient conditions by means of injection rate and momentum flux measurements. Later, the 3D-CFD modeling approach has been validated at steady-state fixed lift conditions. Finally, a previously developed 1D injector model has been used to extract the needle lift profiles and transient pressure boundary conditions used for the full-transient 3D-CFD simulations, using adaptive mesh refinement (AMR) strategies to be able to simulate the complete injection rate starting from 1 mu m lift.This work was partly sponsored by "Ministerio de Economia y Competitividad'', of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor'', Reference TRA2015-67679-c2-1-R. The authors would like also to thank the computer resources, technical expertise and assistance provided by Universidad de Valencia in the use of the supercomputer "Tirant''. Mr. Jaramillo's Thesis is funded by "Conselleria d'Educacio, Cultura i Esports'' of Generalitat Valenciana in the frame of the program "Programa VALI + D para investigadores en formacion, Reference ACIF/2015/040.Salvador, FJ.; De La Morena, J.; Bracho Leon, G.; Jaramillo-Císcar, D. (2018). Computational investigation of diesel nozzle internal flow during the complete injection event. Journal of the Brazilian Society of Mechanical Sciences and Engineering. 40(3):153-167. https://doi.org/10.1007/s40430-018-1074-zS153167403Hall CAS, Lambert JG, Balogh SB (2014) EROI of different fuels and the implications for society. Energy Policy 64:141–152. https://doi.org/10.1016/j.enpol.2013.05.049Lujan JM, Tormos B, Salvador FJ, Gargar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: preliminary study (I). Biomass Bioenergy 33:941–947. https://doi.org/10.1016/j.biombioe.2009.02.004Pickett LM, Siebers DL (2004) Soot in diesel fuel jets: effects of ambient temperature, ambient density, and injection pressure. Combust Flame 138:114–135. https://doi.org/10.1016/j.combustflame.2004.04.006Dec JE (1997) A Conceptual Model of DI Diesel Combustion Based on Laser-Sheet Imaging. SAE Tech. Pap. 970873Wang X, Huang Z, Zhang W et al (2011) Effects of ultra-high injection pressure and micro-hole nozzle on flame structure and soot formation of impinging diesel spray. Appl Energy 88:1620–1628. https://doi.org/10.1016/j.apenergy.2010.11.035Sayin C, Gumus M, Canakci M (2013) Influence of injector hole number on the performance and emissions of a di diesel engine fueled with biodiesel-diesel fuel blends. Appl Therm Eng 61:121–128. https://doi.org/10.1016/j.applthermaleng.2013.07.038Mohan B, Yang W, Chou SK (2013) Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—A review. Renew Sustain Energy Rev 28:664–676. https://doi.org/10.1016/j.rser.2013.08.051Payri R, Salvador FJ, Gimeno J, De la Morena J (2011) Influence of injector technology on injection and combustion development, Part 1: hydraulic characterization. Appl Energy 88:1068–1074. https://doi.org/10.1016/j.apenergy.2010.10.012Park SW, Kim JW, Lee CS (2006) Effect of injector type on fuel-air mixture formation of high-speed diesel sprays. Proc Inst Mech Eng D 220:647–659. https://doi.org/10.1243/09544070D20304Moon S, Komada K, Sato K et al (2015) Ultrafast X-ray study of multi-hole GDI injector sprays: effects of nozzle hole length and number on initial spray formation. Exp Therm Fluid Sci 68:68–81. https://doi.org/10.1016/j.expthermflusci.2015.03.027Powell CF, Kastengren AL, Liu Z, Fezzaa K (2010) The effects of diesel injector needle motion on spray structure. J Eng Gas Turbines Power 133:12802. https://doi.org/10.1115/1.4001073Huang W, Moon S, Ohsawa K (2016) Near-nozzle dynamics of diesel spray under varied needle lifts and its prediction using analytical model. Fuel 180:292–300. https://doi.org/10.1016/j.fuel.2016.04.042Sun Z-Y, Li G-X, Chen C et al (2015) Numerical investigation on effects of nozzle’s geometric parameters on the flow and the cavitation characteristics within injector’s nozzle for a high-pressure common-rail DI diesel engine. Energy Convers Manag 89:843–861. https://doi.org/10.1016/j.enconman.2014.10.047Devassy BM, Habchi C, Daniel E (2015) Atomization modelling of liquid jets using a two-surface density approach. At Sprays 25:47–80Moon S, Gao Y, Park S et al (2015) Effect of the number and position of nozzle holes on in- and near-nozzle dynamic characteristics of diesel injection. Fuel 150:112–122. https://doi.org/10.1016/j.fuel.2015.01.097Payri R, Salvador FJ, Carreres M, De la Morena J (2016) Fuel temperature influence on the performance of a last generation common-rail diesel ballistic injector. Part II: 1D model development, validation and analysis. Energy Convers Manag 114:376–391. https://doi.org/10.1016/j.enconman.2016.02.043Plamondon E, Seers P (2014) Development of a simplified dynamic model for a piezoelectric injector using multiple injection strategies with biodiesel/diesel-fuel blends. Appl Energy 131:411–424. https://doi.org/10.1016/j.apenergy.2014.06.039Postrioti L, Malaguti S, Bosi M et al (2014) Experimental and numerical characterization of a direct solenoid actuation injector for diesel engine applications. Fuel 118:316–328. https://doi.org/10.1016/j.fuel.2013.11.001Desantes JM, Salvador FJ, Lopez JJ, De la Morena J (2011) Study of mass and momentum transfer in diesel sprays based on X-ray mass distribution measurements and on a theoretical derivation. Exp Fluids 50:233–246. https://doi.org/10.1007/s00348-010-0919-8De la Morena J, Neroorkar K, Plazas AH et al (2013) Numerical analysis of the influence of diesel nozzle design on internal flow characteristics for 2-valve diesel engine application. At Sprays 23:97–118. https://doi.org/10.1615/AtomizSpr.2013006361Duke DJ, Schmidt DP, Neroorkar K et al (2013) High-resolution large eddy simulations of cavitating gasoline-ethanol blends. Int J Engine Res 14:578–589. https://doi.org/10.1177/1468087413501824Mitroglou N, McLorn M, Gavaises M et al (2014) Instantaneous and ensemble average cavitation structures in diesel micro-channel flow orifices. Fuel 116:736–742. https://doi.org/10.1016/j.fuel.2013.08.060Wang X, Li K, Su W (2012) Experimental and numerical investigations on internal flow characteristics of diesel nozzle under real fuel injection conditions. Exp Therm Fluid Sci 42:204–211. https://doi.org/10.1016/j.expthermflusci.2012.04.022Sou A, Pratama RH (2016) Effects of asymmetric inflow on cavitation in fuel injector and discharged liquid jet. At Sprays 26:939–959. https://doi.org/10.1615/AtomizSpr.2015013501Xue Q, Battistoni M, Powell CF et al (2015) An Eulerian CFD model and X-ray radiography for coupled nozzle flow and spray in internal combustion engines. Int J Multiph Flow 70:77–88. https://doi.org/10.1016/j.ijmultiphaseflow.2014.11.012Castilla R, Gamez-Montero PJ, Ertrk N et al (2010) Numerical simulation of turbulent flow in the suction chamber of a gearpump using deforming mesh and mesh replacement. Int J Mech Sci 52:1334–1342. https://doi.org/10.1016/j.ijmecsci.2010.06.009Parlak Z, Engin T (2012) Time-dependent CFD and quasi-static analysis of magnetorheological fluid dampers with experimental validation. Int J Mech Sci 64:22–31. https://doi.org/10.1016/j.ijmecsci.2012.08.006Chiatti G, Chiavola O, Palmieri F (2009) Spray modeling for diesel engine performance analysis. SAE Tech Pap 2009-01-0835. https://doi.org/10.4271/2009-01-0835Marcer R, Audiffren C, Viel A, et al (2010) Coupling 1D system AMESim and 3D CFD EOLE models for diesel injection simulation Renault. In: ILASS—Eur. 2010, 23rd Annu. Conf. Liq. At. Spray Syst., pp 1–10Desantes JM, Salvador FJ, Carreres M, Martínez-López J (2014) Large-eddy simulation analysis of the influence of the needle lift on the cavitation in diesel injector nozzles. Proc Inst Mech Eng D 229:407–423. https://doi.org/10.1177/0954407014542627Battistoni M, Xue Q, Som S (2016) Large-eddy simulation (LES) of spray transients: start and end of injection phenomena. Oil Gas Sci Technol 71:24. https://doi.org/10.2516/ogst/2015024CONVERGE is a trade mark of convergent science. https://convergecfd.comMacian V, Bermúdez V, Payri R, Gimeno J (2003) New technique for determination of internal geometry of a diesel nozzle with the use of silicone methodology. Exp Tech 27:39–43. https://doi.org/10.1111/j.1747-1567.2003.tb00107.xDabiri S, Sirignano WA, Joseph DD (2007) Cavitation in an orifice flow. Phys Fluids 19:72112. https://doi.org/10.1063/1.2750655Mohan B, Yang W, Chou SK (2014) Cavitation in injector nozzle holes—a parametric study. Eng Appl Comput Fluid Mech 8:70–81Salvador FJ, Hoyas S, Novella R, Martinez-Lopez J (2011) Numerical simulation and extended validation of two-phase compressible flow in diesel injector nozzles. Proc Inst Mech Eng D 225:545–563. https://doi.org/10.1177/09544070JAUTO1569Som S, Longman DE, Ramirez AI, Aggarwal S (2012) Influence of nozzle orifice geometry and fuel properties on flow and cavitation characteristics of a diesel injector. In: Fuel Inject. Automot. Eng., pp 112–126Desantes JM, Salvador FJ, Carreres M, Jaramillo D (2015) Experimental characterization of the thermodynamic properties of diesel fuels over a wide range of pressures and temperatures. SAE Int J Fuels Lubr 8:2015-01-0951. https://doi.org/10.4271/2015-01-0951Bosch W (1966) The fuel rate indicator: a new measuring instrument for display of the characteristics of individual injection. SAE Pap. 660749Payri R, Salvador FJ, Gimeno J, Bracho G (2008) A new methodology for correcting the signal cumulative phenomenon on injection rate measurements. Exp Tech 32:46–49. https://doi.org/10.1111/j.1747-1567.2007.00188.xPayri F, Payri R, Salvador FJ, Martínez-López J (2011) A contribution to the understanding of cavitation effects in diesel injector nozzles through a combined experimental and computational investigation. Comput Fluids 58:88–101. https://doi.org/10.1016/j.compfluid.2012.01.005Lichtarowicz AK, Duggins RK, Markland E (1965) Discharge coefficients for incompressible non-cavitating flow through long orifices. J Mech Eng Sci 7:210–219. https://doi.org/10.1243/JMES_JOUR_1965_007_029_02Lopez JJ, Salvador FJ, De la Garza OA, Arrègle J (2012) Characterization of the pressure losses in a common rail diesel injector. Proc Inst Mech Eng D 226:1697–1706. https://doi.org/10.1177/0954407012447020Salvador FJ, Carreres M, Jaramillo D, Martínez-López J (2015) Comparison of microsac and VCO diesel injector nozzles in terms of internal nozzle flow characteristics. Energy Convers Manag 103:284–299. https://doi.org/10.1016/j.enconman.2015.05.062LMS (2010) Imagine.Lab AMESim v.10. User’s manualPayri R, Salvador FJ, Martí-Aldaraví P, Martínez-López J (2012) Using one-dimensional modeling to analyze the influence of the use of biodiesels on the dynamic behavior of solenoid-operated injectors in common rail systems: detailed injection system model. Energy Convers Manag 54:90–99. https://doi.org/10.1016/j.enconman.2011.10.00

Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege

Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM) respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM) infected with uropathogenic E. coli (UPEC) revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT) signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13) and PM (IL-3, IL-4, IL-13). NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-α cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key pro-inflammatory cytokines in PM (IL-1α, IL-1β, IL-6 downregulated) and TM (IL-1β, IL-6 upregulated). In addition, unlike PM, LPS-treated TM were refractory to NFκB activation shown by the absence of degradation of IκBα and lack of pro-inflammatory cytokine secretion (IL-6, TNF-α). Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells

Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon

Supplementary Data are available at NAR OnlineThe human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1–72aa) is sufficient for viral transcript elongation and second exon (73–101 aa) appears to contribute to non-transcriptional functions. We observed that Jurkat cells stably expressing intracellular Tat101 showed gene expression deregulation 4-fold higher than cells expressing Tat72. Functional experiments were performed to evaluate the effect of this deregulation. First, NF-iB-, NF-AT- and Sp1-dependent transcriptional activities were greatly enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation. Second, cytoskeleton-related functions as cell morphology, proliferation, chemotaxis, polarization and actin polymerization were deeply altered in Jurkat- Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface receptors was dramatically impaired by intracellular Tat101 but not by Tat72. Consequently, these modifications were greatly dependent on Tat second exon and they could be related to the anergy observed in HIV-1-infected T cells.Plan Nacional del SIDA (MVI 1434/05–5), FIPSE 36584/ 06 and 36633/07, VIRHORST Network from Comunidad de Madrid (Spain), FIS PI040614 and PI0808752, ISCIII-RETIC RD06/0006, EUROPRISE Network of Excellence of the EU (Grant no. LSHP CT-2006- 037611), and BIO2008-04384 from the Ministerio de Ciencia e Innovacio´ n, Espan˜ a. Funding for open access charge: Instituto de Salud Carlos III, Ministry of Science and Technology, Spain.Peer reviewe