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    A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation

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    [EN] Curve squeal is an intense tonal noise occurring when a rail vehicle negotiates a sharp curve. The phenomenon can be considered to be chaotic, with a widely differing likelihood of occurrence on different days or even times of day. The term curve squeal may include several different phenomena with a wide range of dominant frequencies and potentially different excitation mechanisms. This review addresses the different squeal phenomena and the approaches used to model squeal noise; both time-domain and frequency-domain approaches are discussed and compared. Supporting measurements using test rigs and field tests are also summarised. A particular aspect that is addressed is the excitation mechanism. Two mechanisms have mainly been considered in previous publications. In many early papers the squeal was supposed to be generated by the so-called falling friction characteristic in which the friction coefficient reduces with increasing sliding velocity. More recently the mode coupling mechanism has been raised as an alternative. These two mechanisms are explained and compared and the evidence for each is discussed. Finally, a short review is given of mitigation measures and some suggestions are offered for why these are not always successful.Squicciarini, G.; Thompson, D.; Ding, B.; Baeza González, LM. (2018). A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation. Notes on Numerical Fluid Mechanics and Multidisciplinary Design. 139:3-41. https://doi.org/10.1007/978-3-319-73411-8_1S341139Anderson, D., Wheatley, N., Fogarty, B., Jiang, J., Howie, A., Potter, W.: Mitigation of curve squeal noise in Queensland, New South Wales and South Australia. In: Conference on Railway Engineering. pp. 625–636, Perth, Australia (2008)Hanson, D., Jiang, J., Dowdell, B., Dwight, R.: Curve squeal: causes, treatments and results. In INTER-NOISE and NOISE-CON Congress and Conference Proceedings, vol. 249, pp. 6316–6323. Melbourne, Australia (2014)Rudd, M.J.: Wheel/rail noise—part II: wheel squeal. J. Sound Vib. 46(3), 381–394 (1976)Remington, P.J.: Wheel/rail squeal and impact noise: what do we know? What don’t we know? Where do we go from here? J. Sound Vib. 116(2), 339–353 (1987)Remington, P.J.: Wheel/rail rolling noise: what do we know? What don’t we know? Where do we go from here? J. Sound Vib. 120(2), 203–226 (1988)Wickens, A.H.: Fundamentals of Rail Vehicle Dynamics, Guidance and Stability. Swets & Zeitlinger, Lisse (2003)Thompson, D.J.: Railway Noise and Vibration: Mechanisms, Modelling and Mitigation. Elsevier, Oxford (2009)Kalker, J.J.: Three Dimensional Elastic Bodies in Rolling Contact. Kluwer academic publishers, Dordrecht (1990)Vermeulen, P.J., Johnson, K.L.: Contact of nonspherical elastic bodies transmitting tangential forces. J. Appl. Mech. 31(2), 338–340 (1964)Shen, Z.Y., Hedrick, J.K., Elkins, J.A.: A comparison of alternative creep-force models for rail vehicle dynamic analysis. In: Proceedings of 8th IAVSD Symposium, Cambridge MA, Swets and Zeitlinger, Lisse, pp. 591–605 (1983)Huang, Z.Y.: Theoretical Modelling of Railway Curve Squeal. Ph.D. thesis, University of Southampton, UK (2007)Hoffmann, N., Fischer, M., Allgaier, R., Gaul, L.: A minimal model for studying properties of the mode-coupling type instability in friction induced oscillations. Mech. Res. Commun. 29(4), 197–205 (2002)Hoffmann, N., Gaul, L.: Effects of damping on mode-coupling instability in friction induced oscillations. J. Appl. Math. Mech. 83(8), 524–534 (2003)Sinou, J.J., Jezequel, L.: Mode coupling instability in friction-induced vibrations and its dependency on system parameters including damping. Eur. J. Mech.-A/Solids 26(1), 106–122 (2007)Johnson, K.L.: Contact Mechanics. Cambridge University Press, Cambridge (1985)Kinkaid, N.M., O’Reilly, O.M., Papadopoulos, P.: Automotive disc brake squeal. J. Sound Vib. 267(1), 105–166 (2003)Ghazaly, N.M., El-Sharkawy, M., Ahmed, I.: A review of automotive brake squeal mechanisms. J. Mech. Des. Vibr. 1(1), 5–9 (2013)Ouyang, H., Nack, W., Yuan, Y., Chen, F.: Numerical analysis of automotive disc brake squeal: a review. Int. J. Veh. Noise Vib. 1(3–4), 207–231 (2005)Dorf, R.C., Bishop, R.H.: Modern Control Systems, 11th edn. Prentice Hall. (2008)De Beer, F.G., Janssens, M.H.A., Kooijman, P.P., van Vliet, W.J.: Curve squeal of railbound vehicles (part 1): frequency domain calculation model. In: Proceedings of Internoise, vol. 3, pp. 1560–1563. Nice, France (2000)Von Stappenbeck, H.: Das Kurvengeräusch der Straßenbahn. Möglichkeiten zu seiner Unterdrückung. Z. VDI 96(6), 171–175 (1954)Van Ruiten, C.J.M.: Mechanism of squeal noise generated by trams. J. Sound Vib. 120(2), 245–253 (1988)Nakai, M., Chiba, Y., Yokoi, M.: Railway wheel squeal: 1st report, on frequency of squeal. Bull. Jpn. Soc. Mech. Eng. 25, 1127–1134 (1982)Nakai, M., Chiba, Y., Yokoi, M.: Railway wheel squeal: 2nd report, mechanism of specific squeal frequency. Bull. Jpn. Soc. Mech. Eng. 27, 301–308 (1984)Nakai, M., Chiba, Y., Yokoi, M.: Railway wheel squeal: 3rd report, squeal of a disk simulating a wheel in internal resonances. Bull. Jpn. Soc. Mech. Eng. 28, 500–507 (1985)Schneider, E., Popp, K., Irretier, H.: Noise generation in railway wheels due to rail-wheel contact forces. J. Sound Vib. 120(2), 227–244 (1988)Kraft, K.: Der Einfluß der Fahrgeschwindigkeit auf den Haftwert zwischen Rad und Schiene. Arch. für Eisenbahntechnik 22, 58–78 (1967)Fingberg, U.: A model of wheel-rail squealing noise. J. Sound Vib. 143(3), 365–377 (1990)Périard, F.: Wheel-Rail Noise Generation: Curve Squealing by Trams. Ph.D. thesis, Technische Universiteit Delft (1998)Heckl, M.A., Abrahams, I.D.: Curve squeal of train wheels, part 1: mathematical model for its generation. J. Sound Vib. 229(3), 669–693 (2000)Heckl, M.A.: Curve squeal of train wheels, part 2: which wheel modes are prone to squeal? J. Sound Vib. 229(3), 695–707 (2000)Heckl, M.A.: Curve squeal of train wheels: unstable modes and limit cycles. Proc. R. Soc. Lond. A: Math. Phys. Eng. Sci. 458, 1949–1965 (2002)Liu, X., Meehan, P.A.: Wheel squeal noise: a simplified model to simulate the effect of rolling speed and angle of attack. J. Sound Vib. 338, 184–198 (2015)Meehan, P.A., Liu, X.: Analytical prediction and investigation of wheel squeal amplitude. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 69–80. Springer, Heidelberg (2018)Kooijman, P.P., Van Vliet, W.J., Janssens, M.H.A., De Beer, F.G.: Curve squeal of railbound vehicles (part 2): set-up for measurement of creepage dependent friction coefficient. In: Proceedings of Internoise, vol. 3, pp. 1564–1567. Nice, France (2000)De Beer, F.G., Janssens, M.H.A., Kooijman, P.P.: Squeal noise of rail-bound vehicles influenced by lateral contact position. J. Sound Vib. 267(3), 497–507 (2003)Thompson, D.J., Hemsworth, B., Vincent, N.: Experimental validation of the TWINS prediction program for rolling noise, part 1: description of the model and method. J. Sound Vib. 193(1), 123–135 (1996)Monk-Steel, A., Thompson, D.J.: Models for railway curve squeal noise. In: VIII International Conference on Recent Advances in Structural Dynamics, Southampton, UK (2003)Barman, J.F., Katzenelson, J.: A generalized Nyquist-type stability criterion for multivariable feedback systems. Int. J. Control 20(4), 593–622 (1974)Huang, Z.Y., Thompson, D.J., Jones, C.J.C.: Squeal prediction for a bogied vehicle in a curve. In Schulte-Werning, B., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM vol. 99, pp. 313–319. Springer, Heidelberg (2008)Hsu, S.S., Huang, Z., Iwnicki, S.D., Thompson, D.J., Jones, C.J., Xie, G., Allen, P.D.: Experimental and theoretical investigation of railway wheel squeal. Proc. Inst. Mech. Eng. Part F: J. Rail Rapid Transit 221(1), 59–73 (2007)Squicciarini, G., Usberti, S., Thompson, D.J., Corradi, R., Barbera, A.: Curve squeal in the presence of two wheel/rail contact points. In: Nielsen, J.C.O., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 126, pp. 603–610. Springer, Heidelberg (2015)Xie, G., Allen, P.D., Iwnicki, S.D., Alonso, A., Thompson, D.J., Jones, C.J., Huang, Z.Y.: Introduction of falling friction coefficients into curving calculations for studying curve squeal noise. Veh. Syst. Dyn. 44(sup1), 261–271 (2006)Giménez, J.G., Alonso, A., Gómez, E.: Introduction of a friction coefficient dependent on the slip in the FastSim algorithm. Veh. Syst. Dyn. 43(4), 233–244 (2005)Chiello, O., Ayasse, J.B., Vincent, N., Koch, J.R.: Curve squeal of urban rolling stock—part 3: theoretical model. J. Sound Vib. 293(3), 710–727 (2006)Collette, C.: Importance of the wheel vertical dynamics in the squeal noise mechanism on a scaled test bench. Shock Vibr. 19(2), 145–153 (2012)Brunel, J.F., Dufrénoy, P., Naït, M., Muñoz, J.L., Demilly, F.: Transient models for curve squeal noise. J. Sound Vib. 293(3), 758–765 (2006)Glocker, C., Cataldi-Spinola, E., Leine, R.I.: Curve squealing of trains: measurement, modelling and simulation. J. Sound Vib. 324(1), 365–386 (2009)Pieringer, A.: A numerical investigation of curve squeal in the case of constant wheel/rail friction. J. Sound Vib. 333(18), 4295–4313 (2014)Pieringer, A., Kropp, W.: A time-domain model for coupled vertical and tangential wheel/rail interaction—a contribution to the modelling of curve squeal. In: Maeda, T., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 118, pp. 221–229. Springer, Heidelberg (2012)Pieringer, A., Baeza, L., Kropp. W.: Modelling of railway curve squeal including effects of wheel rotation. In: Nielsen, J.C.O., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 126, pp. 417–424. Springer, Heidelberg (2015)Zenzerovic, I., Pieringer, A., Kropp. W.: Towards an engineering model for curve squeal. In: Nielsen, J.C.O., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 126, pp. 433–440. Springer, Heidelberg (2015)Zenzerovic, I., Kropp, W., Pieringer, A.: An engineering time-domain model for curve squeal: tangential point-contact model and Green’s functions approach. J. Sound Vib. 376, 149–165 (2016)Pieringer, A., Torstensson, P.T., Giner, J., Baeza, L.: Investigation of railway curve squeal using a combination of frequency- and time-domain models. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 81–93. Springer, Heidelberg (2018)Chen, G.X., Xiao, J.B., Liu, Q.Y., Zhou. Z.R.: Complex eigenvalue analysis of railway curve squeal. In: Schulte-Werning, B., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 99, pp. 433–439. Springer, Heidelberg (2008)Fourie, D.J., Gräbe, P.J., Heyns, P.S., Fröhling, R.D.: Analysis of wheel squeal due to unsteady longitudinal creepage using the complex eigenvalue method. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 55–67. Springer, Heidelberg (2018)Wang, C., Dwight, R., Li, W., Jiang, J.: Prediction on curve squeal in the case of constant wheel rail friction coefficient. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp XXX–XXX. Springer, Heidelberg (2018)Ding, B., Squicciarini, G., Thompson, D.J.: Effects of rail dynamics and friction characteristics on curve squeal. In: XIII International Conference on Motion and Vibration Control and XII International Conference on Recent Advances in Structural Dynamics (MoViC/RASD), Southampton (2016)Bleedorn, T.G., Johnstone. B.: Steerable steel wheel systems and wheel noise suppression. In: Conference Rec IAS 12th Annual Meeting, Los Angeles, California (1977)Koch, J.R., Vincent, N., Chollet, H., Chiello, O.: Curve squeal of urban rolling stock—part 2: parametric study on a 1/4 scale test rig. J. Sound Vib. 293(3), 701–709 (2006)Logston, C.F., Itami, G.S.: Locomotive friction-creep studies. ASME J. Eng. Ind. 102(3), 275–281 (1980)Ertz, M.: Creep force laws for wheel/rail contact with temperature-dependent coefficient of friction. In: 8th Mini Conference on Vehicle System Dynamics, Identification and Anomalies, Budapest (2002)Lang, W., Roth, R.: Optimale Kraftschlussausnutzung bei Hochleistungs-Schienenfahrzeugen. Eisenbahntechnische Rundsch. 42, 61–66 (1993)Polach, O.: Creep forces in simulations of traction vehicles running on adhesion limit. Wear 258(7), 992–1000 (2005)Zhang, W., Chen, J., Wu, X., Jin, X.: Wheel/rail adhesion and analysis by using full scale roller rig. Wear 253(1), 82–88 (2002)Harrison, H., McCanney, T., Cotter, J.: Recent developments in coefficient of friction measurements at the rail/wheel interface. Wear 253(1), 114–123 (2002)Gallardo-Hernandez, E.A., Lewis, R.: Twin disc assessment of wheel/rail adhesion. Wear 265(9), 1309–1316 (2008)Fletcher, D.I., Lewis, S.: Creep curve measurement to support wear and adhesion modelling, using a continuously variable creep twin disc machine. Wear 298–299, 57–65 (2013)Fletcher, D.I.: A new two-dimensional model of rolling–sliding contact creep curves for a range of lubrication types. Proc. Inst. Mech. Eng. Part J: J. Eng. Tribol. 227(6), 529–537 (2013)Matsumoto, A., Sato, Y., Ono, H., Wang, Y., Yamamoto, M., Tanimoto, M., Oka, Y.: Creep force characteristics between rail and wheel on scaled model. Wear 253(1), 199–203 (2002)Janssens, M.H.A., van Vliet, W.J., Kooijman, P.P., De Beer, F.G.: Curve squeal of railbound vehicles (part 3): measurement method and results. In: Proceedings of Internoise, vol. 3, pp. 1568–1571, Nice, France (2000)Monk-Steel, A.D., Thompson, D.J., De Beer, F.G., Janssens, M.H.A.: An investigation into the influence of longitudinal creepage on railway squeal noise due to lateral creepage. J. Sound Vib. 293(3), 766–776 (2006)Liu, X., Meehan, P.A.: Investigation of the effect of lateral adhesion and rolling speed on wheel squeal noise. Proc. Inst. Mech. Eng. Part F: J. Rail Rapid Transit 227(5), 469–480 (2013)Liu, X., Meehan, P.A.: Investigation of the effect of relative humidity on lateral force in rolling contact and curve squeal. Wear 310(1), 12–19 (2014)Liu, X., Meehan, P.A.: Investigation of squeal noise under positive friction characteristics condition provided by friction modifiers. J. Sound Vib. 371, 393–405 (2016)Jie, E., Kim, J.Y., Hwang, D.H., Lee, J.H., Kim, K.J., Kim, J.C.: An experimental study of squeal noise characteristics for railways using a scale model test rig. In: J. Pombo (ed.) Proceedings of the Third International Conference on Railway Technology: Research, Development and Maintenance, Cagliari, Sardinia, Italy (2016)Eadie, D.T., Santoro, M., Kalousek, J.: Railway noise and the effect of top of rail liquid friction modifiers: changes in sound and vibration spectral distributions in curves. Wear 258(7), 1148–1155 (2005)Bullen, R., Jiang, J.: Algorithms for detection of rail wheel squeal. In: 20th International Congress on Acoustics 2010, ICA 2010—Incorporating Proceedings of the 2010 Annual Conference of the Australian Acoustical Society. pp. 2212–2216 (2010)Stefanelli, R., Dual, J., Cataldi-Spinola, E.: Acoustic modelling of railway wheels and acoustic measurements to determine involved eigenmodes in the curve squealing phenomenon. Veh. Syst. Dyn. 44(sup1), 286–295 (2006)Vincent, N., Koch, J.R., Chollet, H., Guerder, J.Y.: Curve squeal of urban rolling stock—part 1: state of the art and field measurements. J. Sound Vib. 293(3), 691–700 (2006)Anderson, D., Wheatley, N.: Mitigation of wheel squeal and flanging noise on the Australian network. In: Schulte-Werning, B., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 99, pp. 399–405. Springer, Heidelberg (2008)Curley, D., Anderson, D.C., Jiang, J., Hanson, D.: Field trials of gauge face lubrication and top-of-rail friction modification for curve noise mitigation. In: Nielsen, J.C.O., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 126, pp. 449–456. Springer, Heidelberg (2015)Jiang, J., Hanson, D., Dowdell, B.: Wheel squeal—insights from wayside condition monitoring measurements and field trials. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 41–53. Springer, Heidelberg (2018)Jiang, J., Dwight, R., Anderson, D.: Field verification of curving noise mechanisms. In: Maeda, T., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 118, pp. 349–356. Springer, Heidelberg (2012)Jiang, J., Anderson, D.C., Dwight, R.: The mechanisms of curve squeal. In: Nielsen, J.C.O., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 126, pp. 587–594. Springer, Heidelberg (2015)Fourie, D.J., Gräbe, P.J., Heyns, P.S., Fröhling, R.D.: Experimental characterisation of railway wheel squeal occurring in large-radius curves. Proc. Inst. Mech. Eng. Part F: J. Rail Rapid Transit 230(6), 1561–1574 (2016)Corradi, R., Crosio, P., Manzoni, S., Squicciarini, G.: Experimental investigation on squeal noise in tramway sharp curves. In: Proceedings of the 8th International Conference on Structural Dynamics, EURODYN 2011, Leuven (2011)Merideno, I., Nieto, J., Gil-Negrete, N., Landaberea, A., Iartza, J.: Constrained layer damper modelling and performance evaluation for eliminating squeal noise in trams. Shock and Vibration (2014)Nelson J.T.: Wheel/rail noise control manual, TCRP Report 23 (1997)Krüger, F.: Schall- und Erschütterungsschutz im Schienenverkehr. Expert Verlag, Renningen (2001)Elbers, F., Verheijen, E.: Railway noise technical measures catalogue, UIC report UIC003-01-04fe (2013)Oertli, J.: Combatting curve squeal, phase II, final report, UIC (2005)Eadie, D.T., Santoro, M., Powell, W.: Local control of noise and vibration with KELTRACK™ friction modifier and protector® trackside application: an integrated solution. J. Sound Vib. 267(3), 761–772 (2003)Eadie, D.T., Santoro, M.: Top-of-rail friction control for curve noise mitigation and corrugation rate reduction. J. Sound Vib. 293(3), 747–757 (2006)Suda, Y., Iwasa, T., Komine, H., Tomeoka, M., Nakazawa, H., Matsumoto, K., Nakai, T., Tanimoto, M., Kishimoto, Y.: Development of onboard friction control. Wear 258(7), 1109–1114 (2005)Bühler, S., Thallemer, B.: How to avoid squeal noise on railways: state of the art and practical experience. In: Schulte-Werning, B., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 99, pp. 406–411. Springer, Heidelberg (2008)Jones, C.J.C., Thompson, D.J.: Rolling noise generated by railway wheels with visco-elastic layers. J. Sound Vib. 231(3), 779–790 (2000)Wetta, P., Demilly, F.: Reduction of wheel squeal noise generated on curves or during braking. In 11th International of Wheelset Congress, Paris (1995)Brunel, J.F., Dufrénoy, P., Demilly, F.: Modelling of squeal noise attenuation of ring damped wheels. Appl. Acoust. 65(5), 457–471 (2004)Marjani, S.R., Younesian, D.: Suppression of train wheel squeal noise by shunted piezoelectric elements. Int. J. Struct. Stab. Dyn. (2016)Heckl, M.A., Huang, X.Y.: Curve squeal of train wheels, part 3: active control. J. Sound Vib. 229(3), 709–735 (2000)Thompson, D.J., Jones, C.J.C., Waters, T.P., Farrington, D.: A tuned damping device for reducing noise from railway track. Appl. Acoust. 68(1), 43–57 (2007)Jiang, J., Ying, I., Hanson, D., Anderson, D.C.: An investigation of the influence of track dynamics on curve noise. In: Nielsen, J.C.O., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 126, pp. 441–448. Springer, Heidelberg (2015)Toward, M., Squicciarini, G., Thompson, D.J.: Reducing freight wagon noise at source. Int. Railway J. March, 47–49 (2015)Illingworth, R., Pollard, M.G.: The use of steering axle suspensions to reduce wheel and rail wear in curves. Proc. Inst. Mech. Eng. 196(1), 379–385 (1982)Garcia, J.F., Olaizola, X., Martin, L.M., Gimenez, J.G.: Theoretical comparison between different configurations of radial and conventional bogies. Veh. Syst. Dyn. 33(4), 233–259 (2000)Bruni, S., Goodall, R., Mei, T.X., Tsunashima, H.: Control and monitoring for railway vehicle dynamics. Veh. Syst. Dyn. 45(7–8), 743–779 (2007)Hiensch, M., Larsson, P.O., Nilsson, O., Levy, D., Kapoor, A., Franklin, F., Nielsen, J., Ringsberg, J., Josefson, L.: Two-material rail development: field test results regarding rolling contact fatigue and squeal noise behaviour. Wear 258(7), 964–972 (2005)Kopp, E.: Fünf Jahre Erfahrungen mit asymmetrisch geschliffenen Schienenprofilen. Eisenbahn Techn. Rundsch. 40, 665 (1991

    Clinical and electrophysiological features of SCN8A variants causing episodic or chronic ataxia

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    BACKGROUND: Variants in SCN8A are associated with a spectrum of epilepsies and neurodevelopmental disorders. Ataxia as a predominant symptom of SCN8A variation has not been well studied. We set out to investigate disease mechanisms and genotype-phenotype correlations of SCN8A-related ataxia. METHODS: We collected genetic and electro-clinical data of ten individuals from nine unrelated families carrying novel SCN8A variants associated with chronic progressive or episodic ataxia. Electrophysiological characterizations of these variants were performed in ND7/23 cells and cultured neurons. FINDINGS: Variants associated with chronic progressive ataxia either decreased Na + current densities and shifted activation curves towards more depolarized potentials (p.Asn995Asp, p.Lys1498Glu and p.Trp1266Cys) or resulted in a premature stop codon (p.Trp937Ter). Three variants (p.Arg847Gln and biallelic p.Arg191Trp/p.Asp1525Tyr) were associated with episodic ataxia causing loss-of-function by decreasing Na + current densities or a hyperpolarizing shift of the inactivation curve. Two additional episodic ataxia-associated variants caused mixed gain- and loss-of function effects in ND7/23 cells and were further examined in primary murine hippocampal neuronal cultures. Neuronal firing in excitatory neurons was increased by p.Arg1629His, but decreased by p.Glu1201Lys. Neuronal firing in inhibitory neurons was decreased for both variants. No functional effect was observed for p.Arg1913Trp. In four individuals, treatment with sodium channel blockers exacerbated symptoms. INTERPRETATION: We identified episodic or chronic ataxia as predominant phenotypes caused by variants in SCN8A. Genotype-phenotype correlations revealed a more pronounced loss-of-function effect for variants causing chronic ataxia. Sodium channel blockers should be avoided under these conditions. FUNDING: BMBF, DFG, the Italian Ministry of Health, University of Tuebingen

    Deep sequencing reveals the complex and coordinated transcriptional regulation of genes related to grain quality in rice cultivars

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    <p>Abstract</p> <p>Background</p> <p>Milling yield and eating quality are two important grain quality traits in rice. To identify the genes involved in these two traits, we performed a deep transcriptional analysis of developing seeds using both massively parallel signature sequencing (MPSS) and sequencing-by-synthesis (SBS). Five MPSS and five SBS libraries were constructed from 6-day-old developing seeds of Cypress (high milling yield), LaGrue (low milling yield), Ilpumbyeo (high eating quality), YR15965 (low eating quality), and Nipponbare (control).</p> <p>Results</p> <p>The transcriptomes revealed by MPSS and SBS had a high correlation co-efficient (0.81 to 0.90), and about 70% of the transcripts were commonly identified in both types of the libraries. SBS, however, identified 30% more transcripts than MPSS. Among the highly expressed genes in Cypress and Ilpumbyeo, over 100 conserved <it>cis </it>regulatory elements were identified. Numerous specifically expressed transcription factor (TF) genes were identified in Cypress (282), LaGrue (312), Ilpumbyeo (363), YR15965 (260), and Nipponbare (357). Many key grain quality-related genes (i.e., genes involved in starch metabolism, aspartate amino acid metabolism, storage and allergenic protein synthesis, and seed maturation) that were expressed at high levels underwent alternative splicing and produced antisense transcripts either in Cypress or Ilpumbyeo. Further, a time course RT-PCR analysis confirmed a higher expression level of genes involved in starch metabolism such as those encoding ADP glucose pyrophosphorylase (AGPase) and granule bound starch synthase I (GBSS I) in Cypress than that in LaGrue during early seed development.</p> <p>Conclusion</p> <p>This study represents the most comprehensive analysis of the developing seed transcriptome of rice available to date. Using two high throughput sequencing methods, we identified many differentially expressed genes that may affect milling yield or eating quality in rice. Many of the identified genes are involved in the biosynthesis of starch, aspartate family amino acids, and storage proteins. Some of the differentially expressed genes could be useful for the development of molecular markers if they are located in a known QTL region for milling yield or eating quality in the rice genome. Therefore, our comprehensive and deep survey of the developing seed transcriptome in five rice cultivars has provided a rich genomic resource for further elucidating the molecular basis of grain quality in rice.</p

    Between Jacob’s Death and Moses’ Birth: The Intertextual Relationship between Genesis 50:15 – Exodus 1:14 and Jubilees 46:1-16

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    Jacques van Ruiten, “Between Jacob’s Death and Moses’ Birth: The Intertextual Relationship between Genesis 50:15–Exodus 1:14 and Jubilees 46:1–16,” in Flores Florentino: Dead Sea Scrolls and Other Early Jewish Studies in Honour of Florentino García Martínez (ed. Anthony Hilhorst, Émile Puech, and Eibert Tigchelaar; Supplements to the Journal for the Study of Judaism 122; Leiden and Boston: Brill, 2007), 467-489
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