Flame propagation across an obstacle: OH-PLIF and 2-D simulations with detailed chemistry

Flame propagation across a single obstacle inside a closed square channel is studied experimentally and numerically using a stoichiometric H_2/O_2 mixture at initial conditions 15 kPa and 300 K. The 50% blockage obstacle consists of a pair of fence-type obstacles mounted on the top and bottom walls of the channel. Direct optical visualization was performed using single-image measurement of the planar laser-induced fluorescence of the OH radical (OH-PLIF) and simultaneous high-speed schlieren video to study the flame topology and the flame tip velocity along the channel streamwise axis, respectively. The OH-PLIF images provide a novel level of detail and permit a thorough evaluation of the simulation accuracy. The flame tip accelerates to a peak velocity of 590 m/s just downstream of the obstacle followed by a deceleration and subsequent re-acceleration. The unburnt gas flow ahead of the flame is subsonic at all times. The flame does not show any signs of diffusive-thermal instability. Vortex–flame interactions in the recirculation zones downstream of the obstacle wrinkle the flame. The numerical simulations, based on solving the 2-D compressible reactive Navier–Stokes equations with detailed chemistry, predict the flame tip velocity accurately. However, differences in flame topology are observed, specifically, wrinkling is over-estimated. The over-prediction of flame wrinkling suggests a lower dissipation rate in the numerical simulations than in reality, which could be a consequence of neglecting the third channel dimension. Conditional means of the fuel consumption rate are similar to the consumption rates of 1-D unstretched laminar flames at all times. The increase in pressure during flame propagation causes an increase in fuel consumption rate which needs to be accounted for in simplified modeling approaches

The Effect of Cholesterol on the Long-Range Network of Interactions Established among Sea Anemone Sticholysin II Residues at the Water-Membrane Interface

Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol

Analysis of technological knowledge flows in the Basque Country

[EN] Knowledge flow of technology is important for continuous growth and extension of science. Patent data analysis has facilitated this knowledge acquisition. The available patent information crosses borders, corresponds and interacts with new inventions to give new strength and dimension to the technology. Therefore, the patent citation information functions as a key indicator of the knowledge flow providing relevant information. It can be identified to which extent a region is a relevant technological knowledge generator to other regions. As an illustrative case, we present a study to determine the role played by the Basque Country region as a generator of technological innovation during the period 1991-2011.Gavilanes-Trapote, J.; Etxeberria-Agiriano, I.; Cilleruelo, E.; Garechana, G. (2019). Analysis of technological knowledge flows in the Basque Country. International Journal of Production Management and Engineering. 7(Número Especial):73-79. https://doi.org/10.4995/ijpme.2019.10572SWORD73797Número EspecialAcs ZJ, Anselin L, Varga A (2002) Patents and innovation counts as measures of regional production of new knowledge Res. Policy 31:1069-1085. https://doi.org/10.1016/S0048-7333(01)00184-6Balland, P., & Rigby, D. (2017). The geography of complex knowledge. Economic Geography, 93(1), 1-23. https://doi.org/10.1080/00130095.2016.1205947Galvez, C., and Moya-Anegon, F. (2007). Standardizing formats of corporate source data. Scientometrics, 70(1), 3-26. https://doi.org/10.1007/s11192-007-0101-0Gavilanes-Trapote, J., Cilleruelo-Carrasco, E., Etxeberria-Agiriano, I., Garechana, G., Rodríguez Andara, A. (2019). Qualitative Patents Evaluation Through the Analysis of Their Citations. Case of the Technological Sectors in the Basque Country. In: Ortiz, Á., Andrés Romano, C., Poler, R., García-Sabater, J.P. (eds) Engineering Digital Transformation. Lecture Notes in Management and Industrial Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-96005-0_28Gavilanes-Trapote, J., Río-Belver, R. M., Cilleruelo, E., Garechana G., and Larruscain J. (2015). Patent overlay maps: Spain and the basque country. International Journal of Technology Management (IJTM), 69(3/4), 261. https://doi.org/10.1504/IJTM.2015.072976Harhoff, D., Scherer, F., and Vopel, K. (2004). Citations, family size, opposition and the value of patent rights (vol 32, pg 1343, 2003). Research Policy, 33(2), 363-364. https://doi.org/10.1016/j.respol.2003.10.001Higham, K.W., Governale, M., Jaffe, A.B., and Zülicke, U. (2017) Fame and obsolescence: Disentangling growth and aging dynamics of patent citations. Phys. Rev. E 95, 042309. https://doi.org/10.1103/PhysRevE.95.042309Jaffe, A., Trajtenberg, M., and Fogarty, M. (2000). Knowledge spillovers and patent citations: Evidence from a survey of inventors. American Economic Review, 90(2), 215-218. https://doi.org/10.1257/aer.90.2.215Krugman, P. (1995). Development, geography, and economic Theory. Cambridge-Massachusetts: The MIT Press.Malerba, F., and Orsenigo, L. (1995). Schumpeterian patterns of innovation. Cambridge Journal of Economics, 19(1), 47-65. https://doi.org/10.1093/oxfordjournals.cje.a035308Malmberg, A., and Maskell, P. (1997). Towards an explanation of regional specialization and industry agglomeration. European Planning Studies, 5(1), 25-41. https://doi.org/10.1080/09654319708720382Murata, Y., Nakajima, R., Okamoto, R., and Tamura, R. (2014). Localized knowledge spillovers and patent citations: A distance-based approach. Review of Economics and Statistics, 96(5), 967-985. https://doi.org/10.1162/REST_a_00422Organisation for Economic Co-operation and Development (OECD). (2009). OECD patent statistics manual OECD.Podolny, J., Stuart, T., and Hannan, M. (1996). Networks, knowledge, and niches: Competition in the worldwide semiconductor industry, 1984-1991. American Journal of Sociology, 102(3), 659-689. https://doi.org/10.1086/230994Schmoch, U. (2003). Service marks as novel innovation indicator. Research Evaluation, 12(2), 149-156. https://doi.org/10.3152/147154403781776708Simmie, J. (2003). Innovation and urban regions as national and international nodes for the transfer and sharing of knowledge. Regional Studies, 37(6-7), 607-620. https://doi.org/10.1080/0034340032000108714Stek, P.E., and van Geenhuizen, M.S. (2016). The influence of international research interaction on national innovation performance: A bibliometric approach. Technological Forecasting and Social Change, 110, 61-70. https://doi.org/10.1016/j.techfore.2015.09.017Thompson, P., and Fox-Kean, M. (2005). Patent citations and the geography of knowledge spill-overs: A reassessment. American Economic Review, 95(1), 450-460. https://doi.org/10.1257/0002828053828509Thompsori, P. (2006). Patent citations and the geography of knowledge spillovers: Evidence from inventor- and examiner-added citations. Review of Economics and Statistics, 88(2), 383-388. https://doi.org/10.1162/rest.88.2.383You, H., Li, M., Hipel, K.W., Jiang, J., Ge, B., and Duan, H. (2017) Development trend forecasting for coherent light generator technology based on patent citation network analysis. Scientometrics 111(1), 297-315. https://doi.org/10.1007/s11192-017-2252-

Toxin-induced pore formation is hindered by intermolecular hydrogen bonding in sphingomyelin bilayers

Sticholysin I and II (StnI and StnII) are pore-forming toxins that use sphingomyelin (SM) for membrane binding. We examined how hydrogen bonding among membrane SMs affected the StnI- and StnII-induced pore formation process, resulting in bilayer permeabilization. We compared toxin-induced permeabilization in bilayers containing either SM or dihydro-SM (lacking the trans 4 double bond of the long-chain base), since their hydrogen-bonding properties are known to differ greatly. We observed that whereas both StnI and StnII formed pores in unilamellar vesicles containing palmitoyl-SM or oleoyl-SM, the toxins failed to similarly form pores in vesicles prepared from dihydro-PSM or dihydro-OSM. In supported bilayers containing OSM, StnII bound efficiently, as determined by surface plasmon resonance. However, StnII binding to supported bilayers prepared from dihydro-OSM was very low under similar experimental conditions. The association of the positively charged StnII (at pH 7.0) with unilamellar vesicles prepared from OSM led to a concentration-dependent increase in vesicle charge, as determined from zeta-potential measurements. With dihydro-OSM vesicles, a similar response was not observed. Benzyl alcohol, which is a small hydrogen-bonding compound with affinity to lipid bilayer interfaces, strongly facilitated StnII-induced pore formation in dihydro-OSM bilayers, suggesting that hydrogen bonding in the interfacial region originally prevented StnII from membrane binding and pore formation. We conclude that interfacial hydrogen bonding was able to affect the membrane association of StnI- and StnII, and hence their pore forming capacity. Our results suggest that other types of protein interactions in bilayers may also be affected by hydrogen-bonding origination from SMs

Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction

Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oligomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin family, produced by Stichodactyla helianthus. Cholesterol (Chol) is known to enhance the activity of StnII. However, the molecular mechanisms behind this activation have remained obscure, although the activation is not Chol specific but rather sterol specific. To further explore how bilayer lipids affect or are affected by StnII, we have used a multiprobe approach (fluorescent analogs of both Chol and SM) in combination with a series of StnII tryptophan (Trp)-mutants, to study StnII/bilayer interactions. First we compared StnII bilayer permeabilization in the presence of Chol or oleoyl-ceramide (OCer). The comparison was done since both Chol and OCer have a 1-hydroxyl which help to orient the molecule in the bilayer (although OCer have additional polar functional groups). Both Chol and OCer also have increased affinity for SM, which StnII may recognize. However, our results show that only Chol was able to activate StnII-induced bilayer permeabilization – OCer failed to active. To further examine possible Chol/StnII interactions, we measured Förster resonance energy transfer (FRET) between Trp in StnII and cholestatrienol (CTL), a fluorescent analog of Chol. We could show higher FRET efficiency between CTL and Trp:s in position 100 and 114 of StnII, when compared to three other Trp positions further away from the bilayer binding region of StnII. Taken together, our results suggest that StnII was able to attract Chol to its vicinity, maybe by showing affinity for Chol. SM interactions are known to be important for StnII binding to bilayers, and Chol is known to facilitate subsequent permeabilization of the bilayers by StnII. Our results help to better understand the role of these important membrane lipids for the bilayer properties of StnII

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Structural and functional characterization of Sticholysin III: A newly discovered actinoporin within the venom of the sea anemone Stichodactyla helianthus.

Actinoporins are a family of pore-forming toxins produced by sea anemones as part of their venomous cocktail. These proteins remain soluble and stably folded in aqueous solution, but when interacting with sphingomyelin-containing lipid membranes, they become integral oligomeric membrane structures that form a pore permeable to cations, which leads to cell death by osmotic shock. Actinoporins appear as multigenic families within the genome of sea anemones: several genes encoding very similar actinoporins are detected within the same species. The Caribbean Sea anemone Stichodactyla helianthus produces three actinoporins (sticholysins I, II and III; StnI, StnII and StnIII) that differ in their toxic potency. For example, StnII is about four-fold more effective than StnI against sheep erythrocytes in causing hemolysis, and both show synergy. However, StnIII, recently discovered in the S. helianthus transcriptome, has not been characterized so far. Here we describe StnIII’s spectroscopic and functional properties and show its potential to interact with the other Stns. StnIII seems to maintain the well-preserved fold of all actinoporins, characterized by a high content of β-sheet, but it is significantly less thermostable. Its functional characterization shows that the critical concentration needed to form active pores is higher than for either StnI or StnII, suggesting differences in behavior when oligomerizing on membrane surfaces. Our results show that StnIII is an interesting and unexpected piece in the puzzle of how this Caribbean Sea anemone species modulates its venomous activity