Drained cyclic behaviour of loose Dogs Bay sand

The results of drained cyclic triaxial tests performed on Dogs Bay sand (a carbonate sand) are discussed in this paper. For this sand it has been previously demonstrated that the critical state exists and is unique. The relationship between volumetric strains due to cyclic loading and the critical state of this material under monotonic conditions is explored here. Drained cyclic tests on loose samples have been carried out, applying different amplitudes of cyclic loading for samples that generally have initial states on the wet side of critical. The trends of behaviour are summarised, pointing out the relationship between initial state parameter, amplitude of cyclic loading and final change in the state parameter at equilibrium. Experimental evidence is also given to demonstrate that the sand has a memory of the volumetric strain that has previously occurred when different patterns of cyclic loading are consecutively applied and equilibrium has not been reached

A Study of Archiving Strategies in Multi-Objective PSO for Molecular Docking

Molecular docking is a complex optimization problem aimed at predicting the position of a ligand molecule in the active site of a receptor with the lowest binding energy. This problem can be formulated as a bi-objective optimization problem by minimizing the binding energy and the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands. In this context, the SMPSO multi-objective swarm-intelligence algorithm has shown a remarkable performance. SMPSO is characterized by having an external archive used to store the non-dominated solutions and also as the basis of the leader selection strategy. In this paper, we analyze several SMPSO variants based on different archiving strategies in the scope of a benchmark of molecular docking instances. Our study reveals that the SMPSOhv, which uses an hypervolume contribution based archive, shows the overall best performance.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

qKAT: a high-throughput qPCR method for KIR gene copy number and haplotype determination.

Killer cell immunoglobulin-like receptors (KIRs), expressed on natural killer cells and T cells, have considerable biomedical relevance playing significant roles in immunity, pregnancy and transplantation. The KIR locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes KIRs technically laborious and expensive to type. To aid the investigation of KIRs in human disease we developed a high-throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each KIR locus. We used reference DNA samples to validate the accuracy and a cohort of 1698 individuals to evaluate capability for precise copy number discrimination. The method provides improved information and identifies KIR haplotype alterations that were not previously visible using other approaches.This work was funded by the Medical Research Council (MRC) and the Wellcome Trust with partial funding from the National Institute of Health (NIH) Cambridge Biomedical Research Centre and NIH Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT)

Indicación Farmacéutica para el estreñimiento en pacientes con diabetes e hipertensión arterial.

Introducción: El estreñimiento en pacientes con hipertensión arterial o diabetes es un motivo frecuente de consulta al farmacéutico. La indicación farmacéutica no debe interferir con la medicación habitual de estos pacientes. Objetivos: Formular recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico para el estreñimiento. Material y métodos: Mediante revisión sistemática de Guías de Práctica Clínica sobre abordaje del estreñimiento, se han elaborado recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico. Tras diseñar una estrategia de búsqueda, se seleccionaron las fuentes bibliográficas y se llevó a cabo la recogida de información. La búsqueda bibliográfica se realizó en los siguientes recursos web: Medline, GuíaSalud, National Guideline Clearinghouse, Canadian Medical Association Infobase, Scottish Intercollegiate Guidelines Network, Australia’s Clinical Practice Guidelines Portal, Trip Database y National Health Service Evidence. Como fuentes complementarias, se consultó UpToDate, Base de Datos BOT plus 2.0 y un tratado de Farmacología Humana. Resultados: Las recomendaciones se refieren al manejo del estreñimiento idiopático no complicado en pacientes sin síntomas de alarma e incluyen, como tratamiento de primera línea, el consumo de fibra o de agentes formadores de masa. En pacientes que no toleran los laxantes formadores de masa o responden mal a suplementos de fibra, se recomienda el uso de laxantes osmóticos. Por último, si no hay una respuesta satisfactoria, las ecomendaciones incluyen los laxantes estimulantes. En pacientes hipertensos, debe tenerse en cuenta que el hidróxido de magnesio presenta potenciales interacciones con algunos fármacos antihipertensivos. Conclusión: La indicación farmacéutica incluye, como tratamiento de primera línea, suplementos de fibra o agentes formadores de masa. En quienes no los toleran o no responden satisfactoriamente, pueden recomendarse laxantes osmóticos o estimulantes

Indicación Farmacéutica para el estreñimiento en pacientes con diabetes e hipertensión arterial.

Introducción: El estreñimiento en pacientes con hipertensión arterial o diabetes es un motivo frecuente de consulta al farmacéutico. La indicación farmacéutica no debe interferir con la medicación habitual de estos pacientes. Objetivos: Formular recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico para el estreñimiento. Material y métodos: Mediante revisión sistemática de Guías de Práctica Clínica sobre abordaje del estreñimiento, se han elaborado recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico. Tras diseñar una estrategia de búsqueda, se seleccionaron las fuentes bibliográficas y se llevó a cabo la recogida de información. La búsqueda bibliográfica se realizó en los siguientes recursos web: Medline, GuíaSalud, National Guideline Clearinghouse, Canadian Medical Association Infobase, Scottish Intercollegiate Guidelines Network, Australia’s Clinical Practice Guidelines Portal, Trip Database y National Health Service Evidence. Como fuentes complementarias, se consultó UpToDate, Base de Datos BOT plus 2.0 y un tratado de Farmacología Humana. Resultados: Las recomendaciones se refieren al manejo del estreñimiento idiopático no complicado en pacientes sin síntomas de alarma e incluyen, como tratamiento de primera línea, el consumo de fibra o de agentes formadores de masa. En pacientes que no toleran los laxantes formadores de masa o responden mal a suplementos de fibra, se recomienda el uso de laxantes osmóticos. Por último, si no hay una respuesta satisfactoria, las ecomendaciones incluyen los laxantes estimulantes. En pacientes hipertensos, debe tenerse en cuenta que el hidróxido de magnesio presenta potenciales interacciones con algunos fármacos antihipertensivos. Conclusión: La indicación farmacéutica incluye, como tratamiento de primera línea, suplementos de fibra o agentes formadores de masa. En quienes no los toleran o no responden satisfactoriamente, pueden recomendarse laxantes osmóticos o estimulantes

Analyzing policymaking for tuberculosis control in Nigeria

Today, tuberculosis (TB) is still one of the major threats to humankind, being the first cause of death by an infectious disease worldwide. TB is a communicable chronic disease that every year affects 10 million people and kills almost 2 million people in the world. The main key factors fueling the disease are the progressive urbanization of the population and poverty-related socioeconomic factors.Moreover, the lack of effective tools for TB diagnosis, prevention, and treatment has decisively contributed to the lack of an effectivemodel to predict TB spread. In Nigeria, the rapid urbanization along with unprecedented population growth is causing TB to be endemic.This paper proposes a mathematical model to evaluate TB burden in Nigeria by using data obtained from the local TB control program in the community. This research aims to point out effective strategies that could be used to effectively reduce TB burden and death due to TB in this country at different levels.The study shows that efforts should be oriented to more active case finding rather than increasing the treatment effectiveness only. It also reveals that the persistence of the disease is related to a large number of latently infected individuals and quantifies the lives that could be saved by increasing the notification rate using active case finding strategy.We conclude that undiagnosis is the bottleneck that needs to be overcome in addition to the incorporation, improvement, and/or strengthening of treatmentmanagement and other essential TB control measures in Nigeria.Peer ReviewedPostprint (published version

Direct visualization of the native structure of viroid RNAs at single-molecule resolution by atomic force microscopy

[EN] Viroids are small infectious, non-protein-coding circular RNAs that replicate independently and, in some cases, incite diseases in plants. They are classified into two families: Pospiviroidae, composed of species that have a central conserved region (CCR) and replicate in the cell nucleus, and Avsunviroidae, containing species that lack a CCR and whose multimeric replicative intermediates of either polarity generated in plastids self-cleave through hammerhead ribozymes. The compact, rod-like or branched, secondary structures of viroid RNAs have been predicted by RNA folding algorithms and further examined using different in vitro and in vivo experimental techniques. However, direct data about their native tertiary structure remain scarce. Here we have applied atomic force microscopy (AFM) to image at single-molecule resolution different variant RNAs of three representative viroids: potato spindle tuber viroid (PSTVd, family Pospiviroidae), peach latent mosaic viroid and eggplant latent viroid (PLMVd and ELVd, family Avsunviroidae). Our results provide a direct visualization of their native, three-dimensional conformations at 0 and 4 mM Mg2+ and highlight the role that some elements of tertiary structure play in their stabilization. The AFM images show that addition of 4 mM Mg2+ to the folding buffer results in a size contraction in PSTVd and ELVd, as well as in PLMVd when the kissing-loop interaction that stabilizes its 3D structure is preserved.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) grants BIO2016-79618-R (funded by EU under the FEDER programme) to C.B. and BFU2104-56812-P to R.F., as well as by the Comunidad de Madrid grant S2018/NMT-4349 to L.V. CIBERehd is funded by the Instituto de Salud Carlos III (ISCIII).Moreno, M.; Vázquez, L.; López Carrasco, A.; Martín-Gago, JA.; Flores Pedauye, R.; Briones, C. (2019). Direct visualization of the native structure of viroid RNAs at single-molecule resolution by atomic force microscopy. RNA Biology. 16(3):295-308. https://doi.org/10.1080/15476286.2019.1572436S295308163Diener, T. O. (2003). Discovering viroids — a personal perspective. Nature Reviews Microbiology, 1(1), 75-80. doi:10.1038/nrmicro736Flores, R., Hernández, C., Alba, A. E. M. de, Daròs, J.-A., & Serio, F. D. (2005). Viroids and Viroid-Host Interactions. Annual Review of Phytopathology, 43(1), 117-139. doi:10.1146/annurev.phyto.43.040204.140243Ding, B. (2009). The Biology of Viroid-Host Interactions. Annual Review of Phytopathology, 47(1), 105-131. doi:10.1146/annurev-phyto-080508-081927Zhang, Z., Qi, S., Tang, N., Zhang, X., Chen, S., Zhu, P., … Wu, Q. (2014). Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms. PLoS Pathogens, 10(12), e1004553. doi:10.1371/journal.ppat.1004553Serra, P., Messmer, A., Sanderson, D., James, D., & Flores, R. (2018). Apple hammerhead viroid-like RNA is a bona fide viroid: Autonomous replication and structural features support its inclusion as a new member in the genus Pelamoviroid. Virus Research, 249, 8-15. doi:10.1016/j.virusres.2018.03.001Hadidi, A., Barba, M., Hong, N., & Hallan, V. (2017). Apple Scar Skin Viroid. Viroids and Satellites, 217-228. doi:10.1016/b978-0-12-801498-1.00021-8Flores, R., Minoia, S., Carbonell, A., Gisel, A., Delgado, S., López-Carrasco, A., … Di Serio, F. (2015). Viroids, the simplest RNA replicons: How they manipulate their hosts for being propagated and how their hosts react for containing the infection. Virus Research, 209, 136-145. doi:10.1016/j.virusres.2015.02.027Hammann, C., & Steger, G. (2012). Viroid-specific small RNA in plant disease. RNA Biology, 9(6), 809-819. doi:10.4161/rna.19810Kovalskaya, N., & Hammond, R. W. (2014). Molecular biology of viroid–host interactions and disease control strategies. Plant Science, 228, 48-60. doi:10.1016/j.plantsci.2014.05.006Tsagris, E. M., Martínez de Alba, Á. E., Gozmanova, M., & Kalantidis, K. (2008). Viroids. Cellular Microbiology, 10(11), 2168-2179. doi:10.1111/j.1462-5822.2008.01231.xGrill, L. K., & Semancik, J. S. (1978). RNA sequences complementary to citrus exocortis viroid in nucleic acid preparations from infected Gynura aurantiaca. Proceedings of the National Academy of Sciences, 75(2), 896-900. doi:10.1073/pnas.75.2.896Branch, A. D., Benenfeld, B. J., & Robertson, H. D. (1988). Evidence for a single rolling circle in the replication of potato spindle tuber viroid. Proceedings of the National Academy of Sciences, 85(23), 9128-9132. doi:10.1073/pnas.85.23.9128Branch, A. D., & Robertson, H. D. (1984). A Replication Cycle for Viroids and Other Small Infectious RNA’s. Science, 223(4635), 450-455. doi:10.1126/science.6197756Daros, J. A., Marcos, J. F., Hernandez, C., & Flores, R. (1994). Replication of avocado sunblotch viroid: evidence for a symmetric pathway with two rolling circles and hammerhead ribozyme processing. Proceedings of the National Academy of Sciences, 91(26), 12813-12817. doi:10.1073/pnas.91.26.12813Feldstein, P. A., Hu, Y., & Owens, R. A. (1998). Precisely full length, circularizable, complementary RNA: An infectious form of potato spindle tuber viroid. Proceedings of the National Academy of Sciences, 95(11), 6560-6565. doi:10.1073/pnas.95.11.6560Daros, J.-A., & Flores, R. (2004). Arabidopsis thaliana has the enzymatic machinery for replicating representative viroid species of the family Pospiviroidae. Proceedings of the National Academy of Sciences, 101(17), 6792-6797. doi:10.1073/pnas.0401090101Flores, R., Gago-Zachert, S., Serra, P., Sanjuán, R., & Elena, S. F. (2014). Viroids: Survivors from the RNA World? Annual Review of Microbiology, 68(1), 395-414. doi:10.1146/annurev-micro-091313-103416Diener, T. O. (1989). Circular RNAs: relics of precellular evolution? Proceedings of the National Academy of Sciences, 86(23), 9370-9374. doi:10.1073/pnas.86.23.9370Ruiz-Mirazo, K., Briones, C., & de la Escosura, A. (2013). Prebiotic Systems Chemistry: New Perspectives for the Origins of Life. Chemical Reviews, 114(1), 285-366. doi:10.1021/cr2004844Flores, R., Serra, P., Minoia, S., Di Serio, F., & Navarro, B. (2012). Viroids: From Genotype to Phenotype Just Relying on RNA Sequence and Structural Motifs. Frontiers in Microbiology, 3. doi:10.3389/fmicb.2012.00217Steger, G., & Perreault, J.-P. (2016). Structure and Associated Biological Functions of Viroids. Advances in Virus Research, 141-172. doi:10.1016/bs.aivir.2015.11.002Diener, T. O. (1972). Potato spindle tuber viroid. Virology, 50(2), 606-609. doi:10.1016/0042-6822(72)90412-6Gross, H. J., Domdey, H., Lossow, C., Jank, P., Raba, M., Alberty, H., & Sänger, H. L. (1978). Nucleotide sequence and secondary structure of potato spindle tuber viroid. Nature, 273(5659), 203-208. doi:10.1038/273203a0Gast, F.-U., Kempe, D., Spieker, R. L., & Sänger, H. L. (1996). Secondary Structure Probing of Potato Spindle Tuber Viroid (PSTVd) and Sequence Comparison with Other Small Pathogenic RNA Replicons Provides Evidence for Central Non-canonical Base-pairs, Large A-rich Loops, and a Terminal Branch. Journal of Molecular Biology, 262(5), 652-670. doi:10.1006/jmbi.1996.0543Giguère, T., Raj Adkar-Purushothama, C., & Perreault, J.-P. (2014). Comprehensive Secondary Structure Elucidation of Four Genera of the Family Pospiviroidae. PLoS ONE, 9(6), e98655. doi:10.1371/journal.pone.0098655López-Carrasco, A., & Flores, R. (2016). Dissecting the secondary structure of the circular RNA of a nuclear viroid in vivo: A «naked» rod-like conformation similar but not identical to that observed in vitro. RNA Biology, 14(8), 1046-1054. doi:10.1080/15476286.2016.1223005Wang, Y., Zirbel, C. L., Leontis, N. B., & Ding, B. (2018). RNA 3-dimensional structural motifs as a critical constraint of viroid RNA evolution. PLOS Pathogens, 14(2), e1006801. doi:10.1371/journal.ppat.1006801Zhong, X., Leontis, N., Qian, S., Itaya, A., Qi, Y., Boris-Lawrie, K., & Ding, B. (2006). Tertiary Structural and Functional Analyses of a Viroid RNA Motif by Isostericity Matrix and Mutagenesis Reveal Its Essential Role in Replication. Journal of Virology, 80(17), 8566-8581. doi:10.1128/jvi.00837-06Zhong, X., Tao, X., Stombaugh, J., Leontis, N., & Ding, B. (2007). Tertiary structure and function of an RNA motif required for plant vascular entry to initiate systemic trafficking. The EMBO Journal, 26(16), 3836-3846. doi:10.1038/sj.emboj.7601812Zhong, X., Archual, A. J., Amin, A. A., & Ding, B. (2008). A Genomic Map of Viroid RNA Motifs Critical for Replication and Systemic Trafficking. The Plant Cell, 20(1), 35-47. doi:10.1105/tpc.107.056606Hernandez, C., & Flores, R. (1992). Plus and minus RNAs of peach latent mosaic viroid self-cleave in vitro via hammerhead structures. Proceedings of the National Academy of Sciences, 89(9), 3711-3715. doi:10.1073/pnas.89.9.3711Fadda, Z., Daròs, J. A., Fagoaga, C., Flores, R., & Duran-Vila, N. (2003). Eggplant Latent Viroid , the Candidate Type Species for a New Genus within the Family Avsunviroidae (Hammerhead Viroids). Journal of Virology, 77(11), 6528-6532. doi:10.1128/jvi.77.11.6528-6532.2003Navarro, B., & Flores, R. (1997). Chrysanthemum chlorotic mottle viroid: Unusual structural properties of a subgroup of self-cleaving viroids with hammerhead ribozymes. Proceedings of the National Academy of Sciences, 94(21), 11262-11267. doi:10.1073/pnas.94.21.11262Bussière, F., Ouellet, J., Côté, F., Lévesque, D., & Perreault, J. P. (2000). Mapping in Solution Shows the Peach Latent Mosaic Viroid To Possess a New Pseudoknot in a Complex, Branched Secondary Structure. Journal of Virology, 74(6), 2647-2654. doi:10.1128/jvi.74.6.2647-2654.2000GAGO, S. (2005). A kissing-loop interaction in a hammerhead viroid RNA critical for its in vitro folding and in vivo viability. RNA, 11(7), 1073-1083. doi:10.1261/rna.2230605Dube, A., Baumstark, T., Bisaillon, M., & Perreault, J.-P. (2010). The RNA strands of the plus and minus polarities of peach latent mosaic viroid fold into different structures. RNA, 16(3), 463-473. doi:10.1261/rna.1826710Sogo, J. M., Koller, T., & Diener, T. O. (1973). Potato spindle tuber viroid. Virology, 55(1), 70-80. doi:10.1016/s0042-6822(73)81009-8Goodman, T. C., Nagel, L., Rappold, W., Klotz, G., & Riesner, D. (1984). Viroid replication: equilibrium association constant and comparative activity measurements for the viroid-polymerase interaction. Nucleic Acids Research, 12(15), 6231-6246. doi:10.1093/nar/12.15.6231Sanger, H. L., Klotz, G., Riesner, D., Gross, H. J., & Kleinschmidt, A. K. (1976). Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proceedings of the National Academy of Sciences, 73(11), 3852-3856. doi:10.1073/pnas.73.11.3852McClements, W. L., & Kaesberg, P. (1977). Size and secondary structure of potato spindle tuber viroid. Virology, 76(2), 477-484. doi:10.1016/0042-6822(77)90230-6Bustamante, C., & Keller, D. (1995). Scanning Force Microscopy in Biology. Physics Today, 48(12), 32-38. doi:10.1063/1.881478Hansma, H. G., Kasuya, K., & Oroudjev, E. (2004). Atomic force microscopy imaging and pulling of nucleic acids. Current Opinion in Structural Biology, 14(3), 380-385. doi:10.1016/j.sbi.2004.05.005Kuznetsov, Y. G., Daijogo, S., Zhou, J., Semler, B. L., & McPherson, A. (2005). Atomic Force Microscopy Analysis of Icosahedral Virus RNA. Journal of Molecular Biology, 347(1), 41-52. doi:10.1016/j.jmb.2005.01.006Alvarez, D. E., Lodeiro, M. F., Ludueña, S. J., Pietrasanta, L. I., & Gamarnik, A. V. (2005). Long-Range RNA-RNA Interactions Circularize the Dengue Virus Genome. Journal of Virology, 79(11), 6631-6643. doi:10.1128/jvi.79.11.6631-6643.200

Proteomics, a systems biology based approach to investigations of Jatropha curcas seeds

Poster presentation from IUFRO Tree Biotechnology Conference 2011: From Genomes to Integration and Delivery Arraial dAjuda, Bahia, Brazil. 26 June - 2 July 2011(VLID)90651

Implied volatility of basket options at extreme strikes

In the paper, we characterize the asymptotic behavior of the implied volatility of a basket call option at large and small strikes in a variety of settings with increasing generality. First, we obtain an asymptotic formula with an error bound for the left wing of the implied volatility, under the assumption that the dynamics of asset prices are described by the multidimensional Black-Scholes model. Next, we find the leading term of asymptotics of the implied volatility in the case where the asset prices follow the multidimensional Black-Scholes model with time change by an independent increasing stochastic process. Finally, we deal with a general situation in which the dependence between the assets is described by a given copula function. In this setting, we obtain a model-free tail-wing formula that links the implied volatility to a special characteristic of the copula called the weak lower tail dependence function