The R18 polyarginine peptide is more effective than the TAT-NR2B9c (NA-1) peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat

We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO).The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours afterMCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective.The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model.The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke

Poly-arginine peptides reduce infarct volume in a permanent middle cerebral artery rat stroke model

Background: We recently reported that poly-arginine peptides have neuroprotective properties both in vitro and in vivo. In cultured cortical neurons exposed to glutamic acid excitotoxicity, we demonstrated that neuroprotective potency increases with polymer length plateauing at R15 to R18 (R = arginine resides). In an in vivo study in rats, we also demonstrated that R9D (R9 peptide synthesised with D-isoform amino acids) administered intravenously at a dose of 1000 nmol/kg 30 min after permanent middle cerebral artery occlusion (MCAO) reduces infarct volume. Based on these positive in vitro and in vivo findings, we decided to examine the neuroprotective efficacy of the L-isoform poly-arginine peptides, R12, R15 and R18 when administered at a dose of 1000 nmol/kg 30 min after permanent MCAO in the rat. Results: At 24 h post-MCAO, there was reduced total infarct volume for R12 (12.8 % reduction) and R18 (20.5 % reduction), but this reduction only reached statistical significance for R18. Brain slice analysis revealed significantly reduced injury in coronal slices 4 and 5 for R18, and slice 5 for R12. The R15 peptide had no effect on infarct volume. Peptide treatment did not reveal any statistical significant improvement in functional outcomes. Conclusion: While these findings confirm the in vivo neuroprotective properties of poly-arginine peptides, additional dose studies are required particularly in less severe transient MCAO models so as to further assess the potential of these agents as a stroke therapy

Understanding Terrorist Organizations with a Dynamic Model

Terrorist organizations change over time because of processes such as recruitment and training as well as counter-terrorism (CT) measures, but the effects of these processes are typically studied qualitatively and in separation from each other. Seeking a more quantitative and integrated understanding, we constructed a simple dynamic model where equations describe how these processes change an organization's membership. Analysis of the model yields a number of intuitive as well as novel findings. Most importantly it becomes possible to predict whether counter-terrorism measures would be sufficient to defeat the organization. Furthermore, we can prove in general that an organization would collapse if its strength and its pool of foot soldiers decline simultaneously. In contrast, a simultaneous decline in its strength and its pool of leaders is often insufficient and short-termed. These results and other like them demonstrate the great potential of dynamic models for informing terrorism scholarship and counter-terrorism policy making.Comment: To appear as Springer Lecture Notes in Computer Science v2: vectorized 4 figures, fixed two typos, more detailed bibliograph

‘We achieve the impossible’: discourses of freedom and escape at music festivals and free parties

In this article, we explore the notion of freedom as a form of governance within contemporary consumer culture in a sphere where ‘freedom’ appears as a key component: outdoor music-based leisure events, notably music festivals and free parties. ‘Freedom’ is commodified as central to the marketing of many music festivals, which now form a highly commercialised sector of the UK leisure industry, subject to various regulatory restrictions. Free parties, in contrast, are unlicensed, mostly illegal and far less commercialised leisure spaces. We present data from two related studies to investigate how participants at three major British outdoor music festivals and a small rural free party scene draw on discourses of freedom, escape and regulation. We argue that major music festivals operate as temporary bounded spheres of ‘licensed transgression’, in which an apparent lack of regulation operates as a form of governance. In contrast, free parties appear to ‘achieve the impossible’ by creating alternative (and illegal) spaces in which both freedom and regulation are constituted in different ways compared to music festival settings

Multiple shifts and fractional integration in the us and uk unemployment rates

This paper analyses the long-run behaviour of the US and UK unemployment rates by testing for possibly fractional orders of integration and multiple shifts using a sample of over 100 annual observations. The results show that the orders of integration are higher than 0 in both series, which implies long memory. If we assume that the underlying disturbances are white noise, the values are higher than 0.5, i.e., nonstationary. However, if the disturbances are autocorrelated, the orders of integration are in the interval (0, 0.5), implying stationarity and mean-reverting behaviour. Moreover, when multiple shifts are taken into account, unemployment is more persistent in the US than in the UK, implying the need for stronger policy action in the former to bring unemployment back to its original level

Understanding the unsteady pressure field inside combustion chambers of compression-ignited engines using a computational fluid dynamics approach

[EN] In this article, a numerical methodology for assessing combustion noise in compression ignition engines is described with the specific purpose of analysing the unsteady pressure field inside the combustion chamber. The numerical results show consistent agreement with experimental measurements in both the time and frequency domains. Nonetheless, an exhaustive analysis of the calculation convergence is needed to guarantee an independent solution. These results contribute to the understanding of in-cylinder unsteady processes, especially of those related to combustion chamber resonances, and their effects on the radiated noise levels. The method was applied to different combustion system configurations by modifying the spray angle of the injector, evidencing that controlling the ignition location through this design parameter, it is possible to decrease the combustion noise by minimizing the resonance contribution. Important efficiency losses were, however, observed due to the injector/bowl matching worsening which compromises the performance and emissions levels.The authors want to express their gratitude to CONVERGENT SCIENCE Inc. and Convergent Science GmbH for their kind support for performing the CFD calculations using CONVERGE software.Torregrosa, AJ.; Broatch, A.; Margot, X.; Gómez-Soriano, J. (2018). Understanding the unsteady pressure field inside combustion chambers of compression-ignited engines using a computational fluid dynamics approach. International Journal of Engine Research. 1-13. https://doi.org/10.1177/1468087418803030S113Benajes, J., Novella, R., De Lima, D., & Tribotté, P. (2014). Analysis of combustion concepts in a newly designed two-stroke high-speed direct injection compression ignition engine. International Journal of Engine Research, 16(1), 52-67. doi:10.1177/1468087414562867Costa, M., Bianchi, G. M., Forte, C., & Cazzoli, G. (2014). A Numerical Methodology for the Multi-objective Optimization of the DI Diesel Engine Combustion. Energy Procedia, 45, 711-720. doi:10.1016/j.egypro.2014.01.076Navid, A., Khalilarya, S., & Taghavifar, H. (2016). Comparing multi-objective non-evolutionary NLPQL and evolutionary genetic algorithm optimization of a DI diesel engine: DoE estimation and creating surrogate model. Energy Conversion and Management, 126, 385-399. doi:10.1016/j.enconman.2016.08.014Benajes, J., García, A., Pastor, J. M., & Monsalve-Serrano, J. (2016). Effects of piston bowl geometry on Reactivity Controlled Compression Ignition heat transfer and combustion losses at different engine loads. Energy, 98, 64-77. doi:10.1016/j.energy.2016.01.014Masterton, B., Heffner, H., & Ravizza, R. (1969). The Evolution of Human Hearing. The Journal of the Acoustical Society of America, 45(4), 966-985. doi:10.1121/1.1911574Strahle, W. C. (1978). Combustion noise. Progress in Energy and Combustion Science, 4(3), 157-176. doi:10.1016/0360-1285(78)90002-3Flemming, F., Sadiki, A., & Janicka, J. (2007). Investigation of combustion noise using a LES/CAA hybrid approach. Proceedings of the Combustion Institute, 31(2), 3189-3196. doi:10.1016/j.proci.2006.07.060Klos, D., & Kokjohn, S. L. (2014). Investigation of the sources of combustion instability in low-temperature combustion engines using response surface models. International Journal of Engine Research, 16(3), 419-440. doi:10.1177/1468087414556135Cyclic dispersion in engine combustion—Introduction by the special issue editors. (2015). International Journal of Engine Research, 16(3), 255-259. doi:10.1177/1468087415572740Hickling, R., Feldmaier, D. A., & Sung, S. H. (1979). Knock‐induced cavity resonances in open chamber diesel engines. The Journal of the Acoustical Society of America, 65(6), 1474-1479. doi:10.1121/1.382910Torregrosa, A. J., Broatch, A., Margot, X., Marant, V., & Beauge, Y. (2004). Combustion chamber resonances in direct injection automotive diesel engines: A numerical approach. International Journal of Engine Research, 5(1), 83-91. doi:10.1243/146808704772914264Broatch, A., Margot, X., Gil, A., & Christian Donayre, (José). (2007). Computational study of the sensitivity to ignition characteristics of the resonance in DI diesel engine combustion chambers. Engineering Computations, 24(1), 77-96. doi:10.1108/02644400710718583Eriksson, L. J. (1980). Higher order mode effects in circular ducts and expansion chambers. The Journal of the Acoustical Society of America, 68(2), 545-550. doi:10.1121/1.384768Broatch, A., Margot, X., Novella, R., & Gomez-Soriano, J. (2017). Impact of the injector design on the combustion noise of gasoline partially premixed combustion in a 2-stroke engine. Applied Thermal Engineering, 119, 530-540. doi:10.1016/j.applthermaleng.2017.03.081Tutak, W., & Jamrozik, A. (2016). Validation and optimization of the thermal cycle for a diesel engine by computational fluid dynamics modeling. Applied Mathematical Modelling, 40(13-14), 6293-6309. doi:10.1016/j.apm.2016.02.021Payri, F., Benajes, J., Margot, X., & Gil, A. (2004). CFD modeling of the in-cylinder flow in direct-injection Diesel engines. Computers & Fluids, 33(8), 995-1021. doi:10.1016/j.compfluid.2003.09.003Benajes, J., Novella, R., De Lima, D., & Thein, K. (2017). Impact of injection settings operating with the gasoline Partially Premixed Combustion concept in a 2-stroke HSDI compression ignition engine. Applied Energy, 193, 515-530. doi:10.1016/j.apenergy.2017.02.044Lesieur, M., Métais, O., & Comte, P. (2005). Large-Eddy Simulations of Turbulence. doi:10.1017/cbo9780511755507Pope, S. B. (2004). Ten questions concerning the large-eddy simulation of turbulent flows. New Journal of Physics, 6, 35-35. doi:10.1088/1367-2630/6/1/035Silva, C. F., Leyko, M., Nicoud, F., & Moreau, S. (2013). Assessment of combustion noise in a premixed swirled combustor via Large-Eddy Simulation. Computers & Fluids, 78, 1-9. doi:10.1016/j.compfluid.2010.09.034Jamrozik, A., Tutak, W., Kociszewski, A., & Sosnowski, M. (2013). Numerical simulation of two-stage combustion in SI engine with prechamber. Applied Mathematical Modelling, 37(5), 2961-2982. doi:10.1016/j.apm.2012.07.040Qin, W., Xie, M., Jia, M., Wang, T., & Liu, D. (2014). Large eddy simulation of in-cylinder turbulent flows in a DISI gasoline engine. Applied Mathematical Modelling, 38(24), 5967-5985. doi:10.1016/j.apm.2014.05.004Broatch, A., Margot, X., Novella, R., & Gomez-Soriano, J. (2016). Combustion noise analysis of partially premixed combustion concept using gasoline fuel in a 2-stroke engine. Energy, 107, 612-624. doi:10.1016/j.energy.2016.04.045Torregrosa, A. J., Broatch, A., Martín, J., & Monelletta, L. (2007). Combustion noise level assessment in direct injection Diesel engines by means of in-cylinder pressure components. Measurement Science and Technology, 18(7), 2131-2142. doi:10.1088/0957-0233/18/7/045Payri, F., Broatch, A., Margot, X., & Monelletta, L. (2008). Sound quality assessment of Diesel combustion noise using in-cylinder pressure components. Measurement Science and Technology, 20(1), 015107. doi:10.1088/0957-0233/20/1/015107Ihlenburg, F. (2003). The Medium-Frequency Range in Computational Acoustics: Practical and Numerical Aspects. Journal of Computational Acoustics, 11(02), 175-193. doi:10.1142/s0218396x03001900Lapuerta, M., Armas, O., & Hernández, J. J. (1999). Diagnosis of DI Diesel combustion from in-cylinder pressure signal by estimation of mean thermodynamic properties of the gas. Applied Thermal Engineering, 19(5), 513-529. doi:10.1016/s1359-4311(98)00075-1Payri, 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.2011.06.005Payri, F., Broatch, A., Tormos, B., & Marant, V. (2005). New methodology for in-cylinder pressure analysis in direct injection diesel engines—application to combustion noise. Measurement Science and Technology, 16(2), 540-547. doi:10.1088/0957-0233/16/2/029Shahlari, A. J., Hocking, C., Kurtz, E., & Ghandhi, J. (2013). Comparison of Compression Ignition Engine Noise Metrics in Low-Temperature Combustion Regimes. SAE International Journal of Engines, 6(1), 541-552. doi:10.4271/2013-01-1659Yakhot, V., & Orszag, S. A. (1986). Renormalization group analysis of turbulence. I. Basic theory. Journal of Scientific Computing, 1(1), 3-51. doi:10.1007/bf01061452Redlich, O., & Kwong, J. N. S. (1949). On the Thermodynamics of Solutions. V. An Equation of State. Fugacities of Gaseous Solutions. Chemical Reviews, 44(1), 233-244. doi:10.1021/cr60137a013Issa, R. . (1986). Solution of the implicitly discretised fluid flow equations by operator-splitting. Journal of Computational Physics, 62(1), 40-65. doi:10.1016/0021-9991(86)90099-9Dukowicz, J. K. (1980). A particle-fluid numerical model for liquid sprays. Journal of Computational Physics, 35(2), 229-253. doi:10.1016/0021-9991(80)90087-xReitz, R. D., & Beale, J. C. (1999). MODELING SPRAY ATOMIZATION WITH THE KELVIN-HELMHOLTZ/RAYLEIGH-TAYLOR HYBRID MODEL. Atomization and Sprays, 9(6), 623-650. doi:10.1615/atomizspr.v9.i6.40Babajimopoulos, A., Assanis, D. N., Flowers, D. L., Aceves, S. M., & Hessel, R. P. (2005). A fully coupled computational fluid dynamics and multi-zone model with detailed chemical kinetics for the simulation of premixed charge compression ignition engines. International Journal of Engine Research, 6(5), 497-512. doi:10.1243/146808705x30503Pal, P., Keum, S., & Im, H. G. (2015). Assessment of flamelet versus multi-zone combustion modeling approaches for stratified-charge compression ignition engines. International Journal of Engine Research, 17(3), 280-290. doi:10.1177/1468087415571006Torregrosa, A. J., Broatch, A., Gil, A., & Gomez-Soriano, J. (2018). Numerical approach for assessing combustion noise in compression-ignited Diesel engines. Applied Acoustics, 135, 91-100. doi:10.1016/j.apacoust.2018.02.006Torregrosa, A., Olmeda, P., Degraeuwe, B., & Reyes, M. (2006). A concise wall temperature model for DI Diesel engines. Applied Thermal Engineering, 26(11-12), 1320-1327. doi:10.1016/j.applthermaleng.2005.10.021Broatch, A., Javier Lopez, J., García-Tíscar, J., & Gomez-Soriano, J. (2018). Experimental Analysis of Cyclical Dispersion in Compression-Ignited Versus Spark-Ignited Engines and Its Significance for Combustion Noise Numerical Modeling. Journal of Engineering for Gas Turbines and Power, 140(10). doi:10.1115/1.4040287Molina, S., García, A., Pastor, J. M., Belarte, E., & Balloul, I. (2015). Operating range extension of RCCI combustion concept from low to full load in a heavy-duty engine. Applied Energy, 143, 211-227. doi:10.1016/j.apenergy.2015.01.03