Aportación al modelado del motor trifásico de inducción con consideración de la saturación y el efecto de doble jaula

El gran atractivo del modelo estándar del motor de inducción en ejes dq con parámetros constantes reside en su relativa simplicidad, por lo que generalmente se toma como base para la predicción de su conducta dinámica. No obstante, durante transitorios exigentes y en determinadas condiciones de operación, este modelo se revela claramente inadecuado para representar el comportamiento de la máquina.Para paliar este hecho, numerosos esfuerzos se han efectuado para incluir en el modelo del motor efectos tales como el de ranura profunda o la saturación magnética, así como otros fenómenos de segundo orden. No obstante, el enorme incremento en complejidad experimetado por el modelo desincentiva su utilización.En la presente tesis se explora la bondad de determinados modelos simplificados con inclusión del efecto de ranura profunda y la saturación magnética del flujo principal, evaluando bajo qué condiciones su utilización ofrece garantías.Concretamente, se muestra la necesidad del empleo de modelos con inclusión del efecto de ranura profunda para la determinación del tiempo de operación estable del motor trifásico de inducción ante huecos de tensión, evidenciando cómo aun los modelos de orden reducido, mas de doble jaula, predicen resultados acordes con los datos de catálogo suministrados por el fabricante, cometido en el que falla el modelo estándar de jaula sencilla.En lo tocante al modelado de la saturación magnética, se justifica la divergencia en los resultados obtenidos a partir de los modelos con y sin intersaturación cuando estos son formulados en función de determinados conjuntos de variables de estado, a partir de la evaluación de los pesos relativos de los distintos términos que marcan la diferencia entre ambos tipos de modelos, contribuyendo así a clarificar un punto que ha sido objeto de controversia en la literatura especializada. Se efectúa, así mismo, un estudio detallado sobre las implicaciones del uso de parámetros y magnitudes referidos en los modelos con y sin intersaturación, evaluando para qué conjuntos de variables de estado su utilización resulta ventajosa.En suma, queda puesto de manifiesto que haciendo uso de determinados recursos simplificativos, es posible modelar con garantías efectos que en muchas ocasiones son obviados en los modelos para evitar la excesiva complejidad que su inclusión aporta, pero que en aplicaciones concretas resultan esenciales para representar adecuadamente el comportamiento real del motor

La consolidación de la comunidad iberoamericana de Educación Matemática a través de un repositorio digital de documentos

Funes es un repositorio digital de documentos en Educación Matemática que proporciona un espacio virtual en el que profesores, innovadores e investigadores de esta disciplina pueden compartir su producción escrita. El propósito de Funes es contribuir a la consolidación de la comunidad iberoamericana de Educación Matemática. En este documento describimos la taxonomía de términos clave con la que se clasifican los documentos que se incluyen en el repositorio, presentamos sus principales funcionalidades y mostramos sus inicios y evolución en el segundo semestre de 2010

Publicación y búsqueda de investigaciones en educación matemática: el aporte de funes como repositorio digital de documentos

Funes es un repositorio digital de documentos en Educación Matemática que pro-porciona un espacio virtual en el que profesores, innovadores e investigadores de esta disciplina pueden compartir su producción escrita. El propósito de Funes es contribuir a la consolidación de la comunidad iberoamericana de Educación Ma-temática. En este documento presentamos sus principales funcionalidades y mos-tramos sus inicios y evolución durante su primer año de funcionamiento en la red

Is salinity the main ecologic factor that shapes the distribution of two endemic Mediterranean plant species of the genus Gypsophila?

The final publication is available at Springer via http://dx.doi.org/10.1007/s11104-014-2218-2Aims Responses to salt stress of two Gypsophila species that share territory, but with different ecological optima and distribution ranges, were analysed. G. struthium is a regionally dominant Iberian endemic gypsophyte, whereas G. tomentosa is a narrow endemic reported as halophyte. Theworking hypothesis is that salt tolerance shapes the presence of these species in their specific habitats. Methods Taking a multidisciplinary approach, we assessed the soil characteristics and vegetation structure at the sampling site, seed germination and seedling development, growth and flowering, synthesis of proline and cation accumulation under artificial conditions of increasing salt stress and effect of PEG on germination and seedling development. Results Soil salinity was low at the all sampling points where the two species grow, but moisture was higher in the area of G. tomentosa. Differences were found in the species salt and drought tolerance. The different parameters tested did not show a clear pattern indicating the main role of salt tolerance in plant distribution. Conclusions G. tomentosa cannot be considered a true halophyte as previously reported because it is unable to complete its life cycle under salinity. The presence of G. tomentosa in habitats bordering salt marshes is a strategy to avoid plant competition and extreme water stressSoriano, P.; Moruno Manchón, JF.; Boscaiu Neagu, MT.; Vicente Meana, Ó.; Hurtado, A.; Llinares Palacios, JV.; Estrelles, E. (2014). Is salinity the main ecologic factor that shapes the distribution of two endemic Mediterranean plant species of the genus Gypsophila?. Plant and Soil. 384(1-2):363-379. doi:10.1007/s11104-014-2218-2S3633793841-2Alonso MA (1996) Flora y vegetación del Valle de Villena (Alicante). Instituto de Cultura Juan Gil-Albert, AlicanteAlvarado JJ, Ruiz JM, López-Cantarero I, Molero J, Romero L (2000) Nitrogen metabolism in five plant species characteristic of gypsiferous soils. Plant Physiol 156:612–616Ashraf M, Foolad MR (2007) Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot 59:206–216Ashraf MY (2009) Salt tolerance mechanisms in some halophytes from Saudi Arabia and Egypt. Res J Agric Biol Sci 5:191–206Bates LS, Waldren RP, Tear LD (1973) Rapid determination of free proline for water-stress studies. Plant Soil 39:205–207Ben-Gal A, Neori-Borochov H, Yermiyahu U, Shani U (2009) Is osmotic potential a more appropriate property than electrical conductivity for evaluating whole plant response to salinity? Environ Exp Bot 65:232–237Biondi E (2011) Phytosociology today: Methodological and conceptual evolution. Plant Biosyst 145:19–29Boscaiu M, Bautista I, Lidón A, Llinares J, Lull C, Donat P, Mayoral O, Vicente O (2013a) Environmental-dependent proline accumulation in plants living on gypsum soils. Acta Physiol Plant 35:2193–2204Boscaiu M, Llul C, Llinares J, Vicente O, Boira H (2013b) Proline as a biochemical marker in relation to the ecology of two halophytic Juncus species. J Plant Ecol 6:177–186Bradford KJ (1990) A water relations analysis of seed germination rates. Plant Physiol 94:840–849Breckle SW (1999) Halophytic and gypsophytic vegetation of the Ebro-Basin at Los Monegros. In: Melic A, Blasco-Zumeta J (eds) Manifiesto científico por Los Monegros, vol 24, Bol. SEA., pp 101–104Brenchley JL, Probert RJ (1998) Seed germination responses to some environmental factors in the sea grass Zoostera capricorni from eastern Australia. Aquat Bot 62:177–188Cañadas EM, Ballesteros M, Valle F, Lorite J (2013) Does gypsum influence seed germination? Turk J Bot 38:141–147Chen Z, Cuin TA, Zhou M et al (2007) Compatible solute accumulation and stress-mitigating effects in barley genotypes contrasting in their salt tolerance. J Exp Bot 58:4245–4255Chutipaijit S, Cha-Um S, Sompornailin K (2009) Differential accumulation of proline and flavonoids in Indica rice varieties against salinity. Pak J Bot 41:2497–2506Cushman JC (2001) Osmoregulation in plants: implications for agriculture. Am Zool 41:758–769Debussche M, Thompson JD (2003) Habitat differentiation between two closely related Mediterranean plant species, the endemic Cyclamen balearicum and the widespread C. repandum. Acta Oecol 24:35–45Eskandari H, Kazemi K (2011) Germination and seedling properties of different wheat cultivars under salinity conditions. Not Sci Biol 3:130–134FAO (2006) Guidelines for soil descriptions, 5th edn. Food and Agricultural Organization of United Nation, RomeFerrandis P, Herranz JM, Copete MA (2005) Caracterización florística y edáfica de las estepas yesosas de Castilla-La Mancha. Invest Agrar Sist Recur For 14:195–216Flowers TJ, Hall JL (1978) Salt tolerance in Suaeda maritima (L.) Dum. The effect of sodium chloride on growth and soluble enzymes in a comparative study with Pisum sativum L. J Exp Bot 23:310–321Flowers TJ, Colmer TD (2008) Salinity tolerance in halophytes. New Phytol 179:945–963Flowers TJ, Hajibagheri MA, Clipson NJW (1986) Halophytes. Q Rev Biol 61:313–335García-Fuentes A, Salazar C, Torres JA, Cano E, Valle F (2001) Review of communities of Lygeum spartum L. in the south-eastern Iberian Peninsula (western Mediterranean). J Arid Environ 48:323–339Géhu JM (2006) Dictionnaire de Sociologie et Synécologie Végétales. J. Cramer, Berlin-Stuttgart, p 899Géhu JM (2011) On the opportunity to celebrate the centenary of modern phytosociology in 2010. Plant Biosyst 145(suppl):4–8Ghassemi F, Jakeman AJ, Nix HA (1995) Salinisation of land and water resources: human causes, extent, management and case studies. Canberra, Australia. CAB International, The Australian National University, WallingfordGrigore MN, Boscaiu M, Vicente O (2011) Assessment of the relevance of osmolyte biosynthesis for salt tolerance of halophytes under natural conditions. Eur J Plant Sci Biotech 5:12–19Grigore MN, Villanueva M, Boscaiu M, Vicente O (2012a) Do halophytes really require salts for their growth and development? An experimental approach mitigation of salt stress-induced inhibition of Plantago crassifolia reproductive development by supplemental calcium or magnesium. Not Sci Biol 4:23–29Grigore MN, Boscaiu M, Llinares J, Vicente O (2012b) Mitigation of salt stressed-induced Inhibition of Plantago crassifolia reproductive development by supplemental calcium or magnesium. Not Bot Horti Agrobo 40:58–66Hare PD, Cress WA (1997) Metabolic implications of stress-induced proline accumulation in plants. Plant Growth Regul 21:79–102Ishikawa SI, Kachi N (2000) Differential salt tolerance of two Artemisia species growing in contrasting coastal habitats. Ecol Res 15:241–247Kebreab E, Murdoch AJ (1999) Modelling the effects of water stress and temperature on germination rate of Orobanche aegyptiaca seeds. J Exp Bot 50:655–664Khan MA (2002) Halophyte seed germination: Success and Pitfalls. In: Hegazi AM, El-Shaer HM, El-Demerdashe S et al (eds) International symposium on optimum resource utilization in salt affected ecosystems in arid and semi arid regions. Desert Research Centre, Cairo, pp 346–358Khan MA, Gul B, Weber DJ (2000) Germination responses of Salicornia rubra to temperature and salinity. J Arid Environ 45:207–214Khan A, Rayner GD (2003) Robustness to non-normality of common tests for the many-sample location problem. J Appl Math Decis Sci 7:187–206Lidón A, Boscaiu M, Collado F, Vicente O (2009) Soil requirements of three salt tolerant, endemic species from south-east Spain. Not Bot Horti Agrobo 37:64–70López González G (1990) Gypsohila L. In: Castroviejo S, Laínz M, López G et al (eds) Flora Ibérica 2. Real Jardín Botánico, Madrid, pp 408–415Lutts S, Kinet JM, Bouharmont J (1996) Effects of salt stress on growth, mineral nutrition and proline accumulation in relation to osmotic adjustment in rice (Oryza sativa L.) cultivars differing in salinity resistance. Plant Growth Regul 19:207–218Madidi S, Baroudi B, Ameur FB (2004) Effects of salinity on germination and early growth of barley (Hordeum vulgare L.) cultivars. Int J Agric Biol 6:767–770Marchal FM, Lendínez ML, Salazar C, Torres JA (2008) Aportaciones al conocimiento de la vegetación gispsícola en el occidente de la provincia de Granada (sur de España). Lazaroa 29:95–100Médail F, Verlaque R (1997) Ecological characteristics and rarity of endemic plants from southern France and Corsica: implications for biodiversity conservation. Biol Conserv 80:269–281Meyer SE (1986) The ecology of gypsophile endemism in the Eastern Mojave desert. Ecology 67:1303–1313Moruno F, Soriano P, Oscar V, Boscaiu M, Estrelles E (2011) Opportunistic germination behaviour of Gypsophila (Caryophyllaceae) in two priority habitats from semi-arid Mediterranean steppes. Not Bot Horti Agrobo 9:18–23Mota JF, Sánchez Gómez P, Merlo Calvente ME, Catalán Rodríguez P, Laguna Lumbreras E, de la Cruz RM, Navarro Reyes FB, Marchal Gallardo F, Bartolomé Esteban C, Martínez Labarga JM, Sainz Ollero H, Valle Tendero F, Serra Laliga L, Martínez Hernández F, Garrido Becerra JA, Pérez García FJ (2009) Aproximación a la checklist de los gipsófitos ibéricos. An Biol 31:71–80Mota JF, Sola AJ, Jiménez-Sánchez ML, Pérez-García F, Merlo ME (2004) Gypsicolous flora, conservation and restoration of quarries in the southeast of the Iberian Peninsula. Biodivers Conserv 13:1797–1808Munns R (2002) Comparative physiology of salt and water stress. Plant Cell Environ 25:239–250Palacio S, Escudero A, Montserrat-Martí G, Maestro M, Milla R, Albert M (2007) Plants living on gypsum: beyond the specialist model. Ann Bot 99:333–343Peinado M, Martínez-Parras JM (1982) Sobre la posición fitosociológica de Gypsophila tomentosa L. Lazaroa 4:129–140Pueyo Y, Alados CL, Maestro M, Komac B (2007) Gypsophile vegetation patterns under a range of soil properties induced by topographical position. Plant Ecol 189:301–311Rasband WS (1997–2012) ImageJ. U S National Institutes of Health. http://rsb.info.nih.gov/ij/ , Bethesda, MarylandRivas-Martínez S (2005) Notions on dynamic-catenal phytosociology as a basis of landscape science. Plant Biosyst 139:135–144Rivas-Martínez S, Rivas-Saenz S (1996–2009) Worldwide bioclimatic classification system, Phytosociological Research Center, Spain. http://www.globalbioclimatics.org . Accessed 1 July 2013Rivas-Martínez S, Fernández-González F, Loidi J, Lousã M, Penas A (2001) Syntaxonomical checklist of vascular plant communities of Spain and Portugal to association level. Itinera Geobot 14:5–341Salmerón-Sánchez E, Martínez-Nieto MI, Martínez-Hernández F, Garrido-Becerra JA, Mendoza-Fernández AJ, Gil de Carrasco C, Ramos-Miras JJ, Lozano R, Merlo ME, Mota JF (2014) Ecology, genetic diversity and phylogeography of the Iberian endemic plant Jurinea pinnata (Lag.) DC. (Compositae) on two special edaphic substrates: dolomite and gypsum. Plant Soil 374:233–250Saradhi P, Alia P, Arora S, Prasad KV (1995) Proline accumulates in plants exposed to UV radiation and protects them against UV induced peroxidation. Biochem Biophys Res Commun 209:1–5Sekmen AH, Turkan I, Tanyolac ZO, Ozfidan C, Dinc A (2012) Different antioxidant defense responses to salt stress during germination and vegetative stages of endemic halophyte Gypsophila oblanceolata Bark. Environ Exp Bot 77:63–76Tipirdamaz R, Gagneul D, Duhaze C, Ainouche A, Monnier C, Ozkum D, Larher F (2006) Clustering of halophytes from an inland salt marsh in Turkey according to their ability to accumulate sodium and nitrogenous osmolytes. Environ Exp Bot 57:139–153Ungar IA (1996) Effect of salinity on seed germination, growth, and ion accumulation of Atriplex patula (Chenopodiaceae). Am J Bot 83:604–607USDA-ARS (2008) Research databases. Bibliography on salt tolerance. George E. Brown, Jr. Salinity Lab. US Dep. Agric., Agric. Res. Serv. Riverside, CA. http://www.ars.usda.gov/Services/docs.htm?docid=8908USSL Staff (1954) Diagnosis and improvement of saline and alkali soils. US Department of Agriculture Handbook no. 60, 160 ppVicente O, Boscaiu M, Naranjo M, Estrelles E, Bellés JM, Soriano P (2004) Responses to salt stress in the halophyte Plantago crassifolia (Plantaginaceae). J Arid Environ 58:463–48

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Estudio farmacológico de nuevos anticolinesterásicos híbridos tacrina-huperzina A potencialmente útiles para el tratamiento de la enfermedad de Alzheimer

La enfermedad de Alzheimer (AD) es uno de los trastornos neurodegenerativos más importantes que afectan a las personas de edad avanzada, y tan sólo los fármacos anticolinesterásicos han probado tener cierta utilidad en la terapéutica de esta enfermedad. En el presente trabajo de tesis doctoral se han evaluado diversas características farmacológicas de dos nuevos anticolinesterásicos híbridos tacrina-huperzina A, (±)-huprina Y (huprina Y) y (±)-huprina Z (huprina Z). Mediante el método de Ellman se determinó la inhibición de los enzimas acetilcolinesterasa (AChE) bovina y humana y butirilcolinesterasa (BChE) humana. Ambas huprinas resultaron más activas que la tacrina y la huperzina A como inhibidores de la AChE bovina y humana, el mecanismo de inhibición fue de tipo mixto. Además, en los experimentos de reversibilidad de la actividad sobre la AChE bovina, la huprina Y mostró inhibir la enzima con carácter tight-binding. Por otro lado, tanto la huprina Y como la huprina Z actuaron de forma más potente sobre la AChE que sobre la BChE, y de forma más selectiva sobre la AChE humana que sobre la AChE bovina. En los estudios ex vivo realizados en ratón, ambos compuestos mostraron una clara actividad inhibitoria sobre la AChE cerebral, 20 min post-inyección, siendo la huprina Y más potente que la huprina Z [DI50 = 1.09 (0.39-2.98) vs 5.77 (3.29-10.30) mmol/kg]. El tiempo de semivida biológica del efecto fue igual a 1 hora en ambos casos. Se inyectó una única dosis de 10 mmol/kg de diferentes anticolinesterásicos a otro grupo de ratones y se comprobó que la inhibición de la enzima era muy inferior a la mostrada a la misma dosis por las huprinas. Otro aspecto interesante fue observar que las máximas dosis utilizadas de los compuestos (30 mmol/kg huprina Y y 40 mmol/kg huprina Z) sólo producían un ligero aumento de salivación y un leve temblor, mientras que a dosis inferiores de tacrina y huperzina A los efectos indeseables eran muy superiores, llegando en algunos casos a producirse la muerte del animal. A las DI50 calculadas, las huprinas inhibieron la ChE periférica (plasma) con una potencia muy inferior a la mostrada para la AChE central. Por último, se estudió el efecto de estos anticolinesterásicos sobre los receptores muscarínicos. En primer lugar se determinó el desplazamiento de [3H]-pirenzepina y [3H]-QNB, éste último junto a pirenzepina 10 mM, en membranas de hipocampo de rata. Mediante análisis de regresión no lineal se mostró que ambas huprinas tenían una alta afinidad por los receptores muscarínicos M1 (Ki = 2.55 ± 0.89.10-7 huprina Y; 3.89 ± 0.28.10-7 huprina Z), y que esta afinidad era significativamente superior a la que mostraban por los receptores M2 (Ki = 6.91 ± 1.39.10-6 huprina Y; >10-5 huprina Z). A continuación se realizaron estudios de producción de fosfatos de [3H]-inositol inducida por las huprinas con el objeto de discernir si estos compuestos actúan como agonistas o como antagonistas muscarínicos. El carbacol, reconocido agonista muscarínico, mostró una CE50 igual a 8.40 ± 0.42 .10-5 M (efecto revertido en casi su totalidad por los antagonistas atropina y pirenzepina), mientras que el valor para la huprina Y fue de 4.72 ± 1.40 .10-4M y para la huprina Z de 3.80 ± 0.20 .10-4 M. Los aumentos en la producción de fosfatos de [3H]-inositol inducidos por las huprinas fueron revertidos en un 50% por los antagonistas muscarínicos, mientras que el antagonista de los adrenoceptores a1 prazosina revirtió un 30% el efecto, lo cual demuestra que estos fármacos son agonistas muscarínicos M1, pero que además existen otros mecanismos implicados. En resumen, los resultados expuestos en esta tesis doctoral prueban que tanto la huprina Y como la huprina Z son dos potentes anticolinesterásicos, que actúan a nivel del SNC y que presentan un potencial interés para el tratamiento de la EA.Alzheimer disease (AD) is an important neurodegenerative disorder which affects to elderly people and only acetylcholinesterase inhibitors have shown some efficacy in its treatment. This work evaluates some pharmacological characteristics of two new tacrine-huperzine A hybrids, (±)-huprine Y (huprine Y) and (±)-huprine Z (huprine Z). Bovine and human acetylcholinesterase (AChE) and human butyrylcholinesterase (BChE) inhibition were assayed by Ellman's method. The two huprines were more active than both tacrine and huperzine A as inhibitors of both human and bovine AChE, and they acted as mixed-type AChE inhibitors. Moreover, huprine Y exhibited a tight-binding character seen in the experiments of reversibility of bovine AChE inhibitory activity. In addition, both compounds were more active toward AChE than toward BChE. Also, the selectivity for the human AChE was greater than for the bovine enzyme. In ex vivo studies performed in mice, both drugs showed a clear inhibitory activity of brain AChE, 20 min after i.p. injection, huprine Y being more potent than huprine Z [ID50 = 1.09 (0.39-2.98) vs 5.77 (3.29-10.30) mmol/kg]. The time-course study of the inhibitory effect displayed a t1/2 of 1 hour for the two compounds. A single dose (10 mmol/kg) of different anticholinesterasic drugs was administered to another group of mice and in all cases the effect was lower than the effect displayed by huprines at the same dose. Another interesting point was that the huprines at doses as high as 30 and 40 mmol/kg, respectively, only showed slight increases of salivation and some tremors, while tacrine and huperzine A produced higher undesirable effects, and even the death of some animals. The previous ID50 calculated for the huprines were administered to some mice and the inhibitory activity was determined using plasma. Both drugs inhibited the peripheral enzyme with a lower potency than the central ChE. Lastly, the effect on muscarinic receptors was studied. Displacements of [3H]-pirenzepine and [3H]-QNB, this one in presence of pirenzepine 10 mM were performed in membranes of rat hippocampus. Non-linear regression analysis of the curves showed that both drugs had a higher affinity for the M1 receptor (Ki = 2.55 ± 0.89.10-7 huprine Y; 3.89 ± 0.28.10-7 huprine Z) than for the M2 receptor (Ki = 6.91 ± 1.39.10-6 huprine Y; >10-5 huprine Z). Studies of the huprines production of [3H]-inositol phosphates were done in order to know wheter these drugs act as agonist or antagonist of M1 receptors. Carbachol, a well-known muscarinic agonist, showed a EC50 of 8.40 ± 0.42 .10-5 M (effect reverted in almost 100% by muscarinic antagonist atropine and pirenzepine), while EC50 were 4.72 ± 1.40 .10-4M and 3.80 ± 0.20 .10-4 M for the huprine Y and the huprine Z, respectively. The increases of inositol phosphates production induced by the drugs were antagonized in a 50% in both cases by the muscarinic antagonist. On the other hand, prazosine, an a1-adrenoceptor antagonist, reverted 30% of the effect, which proves that huprines are muscarinic M1 agonists, but there are other mechanisms involved in the production of inositol phosphates. In summary, these results show that huprine Y and huprine Z are two potent anticholinesterasic drugs, which act at CNS and which are of potential interest in the treatment of the AD

Near Infrared Spectroscopy : A useful technique for inline monitoring of the enzyme catalyzed biosynthesis of third-generation biodiesel from waste cooking oil

Acord transformatiu CRUE-CSICNear Infrared (NIR) spectroscopy was used for inline monitoring the enzymatic production of third-generation biodiesel from waste cooking oil (WCO) -with fatty acid profile similar to olive oil- under the principles of Continued Process Verification (CPV) and Process Analytical Technology (PAT). For this purpose, covalently immobilized mature Rhizopus oryzae lipase (rROL) was used to transesterify WCO with methanol and ethanol, firstly in 10 mL vials under orbital stirring and then it was successfully scaled up to a mechanically stirred 50 mL laboratory reactor specially designed for use of a NIR probe. Biocatalyst half-life and productivity after ten reaction cycles with methanol and ethanol were assessed. Slightly higher operational stability with methanol (337.5 h, 54 batches) vs with ethanol (146.7 h, 44 batches) was observed, but decreased productivity as a result of the increased reaction times used with the former (219 vs 327 µmol min). The NIR spectroscopy results were highly correlated with those of gas chromatography (GC) used as reference. Thus, the root mean-square standard error of prediction (RMSEP) was 2.0% for methanol and 2.1% for ethanol. Therefore, NIR spectroscopy, which allows data acquisition in real time, is suitable for inline monitoring of enzymatic production of biodiesel