25 research outputs found

    A structural annotation resource for the selection of putative target proteins in the malaria parasite

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    <p>Abstract</p> <p>Background</p> <p>Protein structure plays a pivotal role in elucidating mechanisms of parasite functioning and drug resistance. Moreover, protein structure aids the determination of protein function, which can together with the structure be used to identify novel drug targets in the parasite. However, various structural features in <it>Plasmodium falciparum </it>proteins complicate the experimental determination of protein structures. Limited similarity to proteins in the Protein Data Bank and the shortage of solved protein structures in the malaria parasite necessitate genome-scale structural annotation of <it>P. falciparum </it>proteins. Additionally, the annotation of a range of structural features facilitates the identification of suitable targets for experimental and computational studies.</p> <p>Methods</p> <p>An integrated structural annotation system was developed and applied to <it>P. falciparum</it>, <it>Plasmodium vivax </it>and <it>Plasmodium yoelii</it>. The annotation included searches for sequence similarity, patterns and domains in addition to the following predictions: secondary structure, transmembrane helices, protein disorder, low complexity, coiled-coils and small molecule interactions. Subsequently, candidate proteins for further structural studies were identified based on the annotated structural features.</p> <p>Results</p> <p>The annotation results are accessible through a web interface, enabling users to select groups of proteins which fulfil multiple criteria pertaining to structural and functional features <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Analysis of features in the <it>P. falciparum </it>proteome showed that protein-interacting proteins contained a higher percentage of predicted disordered residues than non-interacting proteins. Proteins interacting with 10 or more proteins have a disordered content concentrated in the range of 60–100%, while the disorder distribution for proteins having only one interacting partner, was more evenly spread.</p> <p>Conclusion</p> <p>A series of <it>P. falciparum </it>protein targets for experimental structure determination, comparative modelling and <it>in silico </it>docking studies were putatively identified. The system is available for public use, where researchers may identify proteins by querying with multiple physico-chemical, sequence similarity and interaction features.</p

    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. 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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. 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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. 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    Role of ADAM and ADAMTS metalloproteinases in airway diseases

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    Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase and disintegrin domains endowing them with features of both proteinases and adhesion molecules. Proteinases of the ADAM family are associated to various physiological and pathological processes and display a wide spectrum of biological effects encompassing cell fusion, cell adhesion, "shedding process", cleavage of various substrates from the extracellular matrix, growth factors or cytokines... This review will focus on the putative roles of ADAM/ADAMTS proteinases in airway diseases such as asthma and COPD

    Condrodisplasia punctata rizomélica: relato de caso e breve revisão da literatura Rhizomelic chondrodysplasia punctata: a case report and brief literature review

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    Apresentamos um caso de uma lactente de dois meses de idade acometida pela forma recessiva da condrodisplasia punctata, doença caracterizada, radiologicamente, por acentuado encurtamento proximal e distúrbio de ossificação (epífises puntiformes) dos membros. São enfatizados os achados clínico-radiológicos, bem como seus principais diagnósticos diferenciais, baseados em dados de breve revisão da literatura.<br>The authors present a case of a 2-month-old infant affected by the recessive form of chondrodysplasia punctata, a rare condition radiologically characterized by severe proximal shortening and anomalous ossification (epiphyseal stippling) of the limbs. Clinical and radiological findings as well as main differential diagnoses are emphasized on the basis of data originating from a brief literature review

    Is microclimate-driven turnover of dung beetle assemblage structure in regenerating coastal vegetation a precursor to re-establishment of a forest fauna?

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    We questioned the capability of post-mining rehabilitation and successional changes in coastal vegetation to achieve restoration of dune forest, dung beetle assemblages in the Maputaland Centre of Endemism, South Africa. A repeat 2010 study of structural turnover between dung beetle assemblages across a 33 year successional sere of rehabilitating vegetation and old-growth forest (>73 years) produced comparable results to an earlier study across the 23 year chronosequence of 2000. Despite overlap, three structural patterns along the 33 year chronosequence were associated with specific stages of vegetation succession and their characteristic microclimates as in 2000. Although species biased to unshaded habitat dominated the earliest succession, there was rapid re-establishment of dominance by shade-associated forest species. In concert with progression from unshaded, post-mining vegetation to strongly shaded, early successional, Acacia shrub-woodland, there was an initial increase in similarity of the dung beetle fauna (species-poor, low abundance) to that in strongly-shaded forest (also species-poor, low abundance). However, in concert with decreasing shade cover in late successional woodland, the dung beetle fauna became species-rich with high abundance so that the early successional trajectory of increasing similarity to forest fauna either levelled off to a plateau (species in 2000; abundance in 2010) or declined (species in 2010, abundance in 2000). It remains to be seen if gaps forming in the oldest Acacia woodland permit forest tree saplings of the exposed understorey to recreate a forest canopy that would be tracked by dung beetles to re-establish a typically species-poor, deep shade, forest assemblage with low abundance.The study was funded through grants to RJvA from Richards Bay Minerals, the Department of Trade and Industry (THRIP), and the National Research Foundation (NRF).http://www.springerlink.com/content/100177/hb2013ab201
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