Aproximacions sintètiques per a la preparació estereoselectiva de noves quinolil i pirazolilglicines i per a la preparació en fase sòlida de llibreries de benzotiazoles, 1,2,4-triazines i benzimidazoles

El treball experimental que ha permès redactar la present Tesi Doctoral ha estat dividit en dues parts. A la primera part es presenten els resultats referents a la síntesi estereocontrolada de noves heteroarilglicines (quinolil i pirazolilglicines) a partir de cetones acetilèniques, substrats quirals que permeten accedir a l'esquelet de diferents heterocicles (quinolines i pirazoles), la posterior obtenció dels corresponents quinolil i pirazolil--aminoalcohols i les diferents metodologies d'oxidació per tal d'accedir a les corresponents quinolil i priazolilglicines objectiu. A la segona part d'aquesta memòria s'ha estudiat, en dissolució, l'habilitat del grup alquilsulfona com a grup sortint eficaç en reaccions d'ipso-substitució nucleofilica. El desenvolupament d'aquesta reacció ha servit de punt de partida per a la creació de llibreries d'heterocicles amb alta diversitat molecular i potencial interès biològic sobre fase sòlida.

Influencia de la suplementación de antioxidantes y de la administración de enrofloxacina en la calidad y seguridad de la carne de ave

Los fenómenos oxidativos y en particular la oxidación lipídica son uno de los principales responsables de la pérdida de calidad en la carne y en los productos cárnicos. Como consecuencia de estos procesos se generan compuestos que pueden afectar el flavor, color y textura de la carne disminuyendo la aceptabilidad por parte del consumidor y reduciendo su valor nutritivo. Por otro lado, el estrés oxidativo está relacionado con la etiología de diversas enfermedades comunes en nuestra sociedad. Las carnes de pollo y de pavo son particularmente sensibles a los procesos oxidativos debido a su elevada proporción de ácidos grasos poliinsaturados en comparación con otros tipos de carne. La suplementación de antioxidantes en la dieta de determinados animales es una de las estrategias más eficaces para proteger la carne de la oxidación. Otro aspecto que afecta a la calidad y seguridad de la carne es la presencia de residuos en los tejidos animales destinados al consumo humano, una parte de los cuáles puede proceder de la administración de antibióticos. En este trabajo se estudió la eficacia de tres compuestos antioxidantes, alfa-tocoferol, beta-caroteno y licopeno, adicionados en distintas concentraciones y combinaciones a la dieta de pollos y pavos. Para ello se determinó la estabilidad oxidativa de los tejidos musculares de pechuga y muslo mediante el análisis de los valores de TBARS, de las actividades de los enzimas antioxidantes GSHPx, CAT y SOD y desde un punto de vista sensorial. Asimismo, se analizaron las concentraciones de vitamina E presentes en ambos músculos. Por otro lado, se investigó la presencia de residuos del antibiótico enrofloxacina y de su metabolito en los tejidos muscular y hepático de ambas especies después de la administración del fármaco con o sin periodo de retirada. Finalmente, y dada la aparente relación existente entre el metabolismo de determinados antibióticos y los fenómenos oxidativos, se valoró la posible interacción entre el fármaco y la vitamina E suplementada a la dieta. La vitamina E, a dosis de 100 ppm y 200 ppm en pollos y pavos respectivamente, se comportó como un antioxidante eficaz disminuyendo la rancidez de la carne tanto en pechuga como en muslo. La dosis de vitamina E necesaria para conseguir un incremento significativo de la estabilidad oxidativa de la carne varió en función de la especie y de las características bioquímicas del tejido analizado. El beta-caroteno, suplementado en la dieta de pollos y pavos conjuntamente con la vitamina E, no sólo no manifestó propiedades antioxidantes sino que enmascaró la efectividad de la vitamina E. El licopeno, de cuya utilización en nutrición animal no existían estudios publicados anteriormente, no mostró eficacia antioxidante en la carne de pollo a una dosis de 10 ppm. Respecto al análisis de residuos de antibiótico se observó que tras el periodo de retirada del fármaco los niveles residuales de enrofloxacina y su metabolito disminuyeron notablemente. Debe tenerse en cuenta que se apreciaron diferencias en función de la especie y del tejido considerados, estando los residuos en algunos casos por encima de los límites máximos permitidos. Por otro lado, se observó una relación entre la enrofloxacina y la vitamina E suplementada en la dieta que, parecía depender tanto de la dosis de antioxidante como del metabolismo del fármaco. Esta interacción afectó tanto a los niveles de vitamina E como a la presencia de residuos de enrofloxacina en el tejido muscular, resaltando la importancia de no subestimar posibles interacciones entre distintos compuestos presentes en la dieta animal.

Hemispheric asymmetries in recognition memory for negative and neutral words

Federmeier and Benjamin (2005) have suggested that semantic encoding for verbal information in the right hemisphere can be more effective when memory demands are higher. However, other studies (Kanske & Kotz, 2007) also suggest that visual word recognition differ in function of emotional valence. In this context, the present study was designed to evaluate the effects of retention level upon recognition memory processes for negative and neutral words. Sample consisted of 15 right-handed undergraduate portuguese students with normal or corrected to normal vision. Portuguese concrete negative and neutral words were selected in accordance to known linguistic capabilities of the right hemisphere. The participants were submitted to a visual half-field word presentation using a continuous recognition memory paradigm. Eye movements were continuously monitored with a Tobii T60 eye-tracker that showed no significant differences in fixations to negative and neutral words. Reaction times in word recognition suggest an overall advantage of negative words in comparison to the neutral words. Further analysis showed faster responses for negative words than for neutral words when were recognised at longer retention intervals for left-hemisphere encoding. Electrophysiological data through event related potentials revealed larger P2 amplitude over centro-posterior electrode sites for words studied in the left hemifield suggesting a priming effect for right-hemisphere encoding. Overall data suggest different hemispheric memory strategies for the semantic encoding of negative and neutral words.

Synteza analogów nukleozydów i pronukleotydów z zastosowaniem reakcji Huisgena katalizowanej jonami miedzi(I) oraz badania ich aktywności biologicznej

Wydział Chemii: Pracownia Chemii Nukleozydów i Nukleotydów

Por media vida deslumbrados (Dossier: Narradores ecuatorianos de la década de 1950)

En este trabajo se plantea que acaso con mayor intensidad que en Huasipungo (1934) y El Chulla Romero y Flores (1958), es en tres obras poco estudiadas de Jorge Icaza donde puede apreciarse con claridad –tal que deslumbra– su propuesta estética: en la pieza de teatro Flagelo (1936), la novela Media vida deslumbrados (1942) y el cuento «El nuevo San Jorge» (1952). Sin apartarse de la denuncia social, Icaza cierra con Flagelo su propuesta dramática, constituyen una suerte de manifiesto literario, por las repercusiones estéticas que alcanzan a la narrativa del autor. En Media vida deslumbrados se puede apreciar un equilibrio efectivo entre las propuestas del autor y su afán de denuncia social. «El nuevo San Jorge», según el autor de este ensayo, sería la obra que alberga lo más radical, en cuanto propuesta estética, de toda la obra icaciana, destaca los elementos neo-barrocos de la misma, con insistencia en los juegos de máscaras, las intermitencias entre las luces y las sombras, y en el múltiple y a la vez unívoco rostro de quien detenta el poder –algunos de estos elementos comunes a las dos obras comentadas, y a El Chulla Romero y Flores.

Detection of flood extent in urban areas using high resolution TerraSAR-X data

Flooding is a major hazard in both rural and urban areas worldwide, but it is in urban areas that the impacts are most severe. An investigation of the ability of high resolution TerraSAR-X data to detect flooded regions in urban areas is described. An important application for this would be the calibration and validation of the flood extent predicted by an urban flood inundation model. To date, research on such models has been hampered by lack of suitable distributed validation data. The study uses a 3m resolution TerraSAR-X image of a 1-in-150 year flood near Tewkesbury, UK, in 2007, for which contemporaneous aerial photography exists for validation. The DLR SETES SAR simulator was used in conjunction with airborne LiDAR data to estimate regions of the TerraSAR-X image in which water would not be visible due to radar shadow or layover caused by buildings and taller vegetation, and these regions were masked out in the flood detection process. A semi-automatic algorithm for the detection of floodwater was developed, based on a hybrid approach. Flooding in rural areas adjacent to the urban areas was detected using an active contour model (snake) region-growing algorithm seeded using the un-flooded river channel network, which was applied to the TerraSAR-X image fused with the LiDAR DTM to ensure the smooth variation of heights along the reach. A simpler region-growing approach was used in the urban areas, which was initialized using knowledge of the flood waterline in the rural areas. Seed pixels having low backscatter were identified in the urban areas using supervised classification based on training areas for water taken from the rural flood, and non-water taken from the higher urban areas. Seed pixels were required to have heights less than a spatially-varying height threshold determined from nearby rural waterline heights. Seed pixels were clustered into urban flood regions based on their close proximity, rather than requiring that all pixels in the region should have low backscatter. This approach was taken because it appeared that urban water backscatter values were corrupted in some pixels, perhaps due to contributions from side-lobes of strong reflectors nearby. The TerraSAR-X urban flood extent was validated using the flood extent visible in the aerial photos. It turned out that 76% of the urban water pixels visible to TerraSAR-X were correctly detected, with an associated false positive rate of 25%. If all urban water pixels were considered, including those in shadow and layover regions, these figures fell to 58% and 19% respectively. These findings indicate that TerraSAR-X is capable of providing useful data for the calibration and validation of urban flood inundation models.

Spatial and temporal scale issues in determining biomass burning regimes in Bolivia and Peru

ATSR-2 active fire data from 1996 to 2000, TRMM VIRS fire counts from 1998 to 2000 and burn scars derived from SPOT VEGETATION ( the Global Burnt Area 2000 product) were mapped for Peru and Bolivia to analyse the spatial distribution of burning and its intra- and inter-annual variability. The fire season in the region mainly occurs between May and October; though some variation was found between the six broad habitat types analysed: desert, grassland, savanna, dry forest, moist forest and yungas (the forested valleys on the eastern slope of the Andes). Increased levels of burning were generally recorded in ATSR-2 and TRMM VIRS fire data in response to the 1997/1998 El Nino, but in some areas the El Nino effect was masked by the more marked influences of socio-economic change on land use and land cover. There were differences between the three global datasets: ATSR-2 under-recorded fires in ecosystems with low net primary productivities. This was because fires are set during the day in this region and, when fuel loads are low, burn out before the ATSR-2 overpass in the region which is between 02.45 h and 03.30 h. TRMM VIRS was able to detect these fires because its overpasses cover the entire diurnal range on a monthly basis. The GBA2000 product has significant errors of commission (particularly areas of shadow in the well-dissected eastern Andes) and omission (in the agricultural zone around Santa Cruz, Bolivia and in north-west Peru). Particular attention was paid to biomass burning in high-altitude grasslands, where fire is an important pastoral management technique. Fires and burn scars from Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper (ETM) data for a range of years between 1987 and 2000 were mapped for areas around Parque Nacional Rio Abiseo (Peru) and Parque Nacional Carrasco (Bolivia). Burn scars mapped in the grasslands of these two areas indicate far more burning had taken place than either the fires or the burn scars derived from global datasets. Mean scar sizes are smaller and have a smaller range in size between years the in the study area in Peru (6.6-7.1 ha) than Bolivia (16.9-162.5 ha). Trends in biomass burning in the two highland areas can be explained in terms of the changing socio-economic environments and impacts of conservation. The mismatch between the spatial scale of biomass burning in the high-altitude grasslands and the sensors used to derive global fire products means that an entire component of the fire regime in the region studied is omitted, despite its importance in the farming systems on the Andes.

The influence of affective statements on performance on implicit and explicit memory tasks

Consumers are often exposed to brand names presented concurrently with information such as brand claims and warnings, prior to making product choices. As implicit memory has been implicated in the consumer choice process, two experiments were conducted to assess the influence of additional information, namely simple positive and negative statements, on implicit and explicit memory tasks. In Experiment 1, the mere presence of additional statements at study significantly reduced performance on a two-alternatives forced recognition task. However, the same manipulation had no effect on implicit preference judgement task performance. The valence of the accompanying information had no effect on either task. In Experiment 2, using modified implicit and explicit choice tasks, performance on the former was unaffected by statement valence, whereas the latter task was. Hence, positive priming was obtained for brand names previously shown with negative information. The results of the experiments are discussed in relation to both implicit memory and consumer choice.

Transfer effects in implicit memory and consumer choice

Two experiments investigated transfer effects in implicit memory and consumer choice, using a preference judgement task. Experiment 1 examined whether it is possible to obtain priming for unfamiliar food labels. Additionally, it investigated whether the experience of seeing a brand name with a particular product type would benefit subsequent processing of the brand name when linked with a different product type. Experiment 2 examined whether changes in modality between study and test would affect priming for unfamiliar brand names. Both questions are theoretically important, as well as pertaining to practical concerns in the consumer choice literature. Experiment 1 demonstrated significant priming for unfamiliar food labels, and established that priming was unaffected by changing the product type with which the brand name was associated. In Experiment 2, priming on both auditory and visual versions of the preference judgement task was reduced by changes in modality. The results and implications are discussed in relation to consumer choice and current theories of implicit memory.

Self-activation and out-group contrast

It has been suggested that higher in-group identifiers primed with an out-group stereotype show contrastive behavioral responses because they activate the in-group, social-self. However, priming the personal-self can lead to contrastive judgments. We investigated whether personal self-activation was also evident for higher identifiers primed with an out-group. An experiment demonstrated that higher identifiers primed with an out-group showed faster responses to self-words than higher identifiers primed with the in-group. This findings suggest that the personal-self is also activated for higher identifiers primed with an out-group, and this self-activation may underlie their contrastive responding.

Post-abscission, pre-dispersal seeds of Digitalis purpurea remain in a developmental state that is not terminated by desiccation ex planta

Seed quality may be compromised if seeds are harvested before natural dispersal (shedding). It has been shown previously that slow or delayed drying can increase potential quality compared with immediate rapid drying. This study set out to investigate whether or not there is a critical moisture content, below which drying terminates maturation events for seeds harvested after mass maturity but before dispersal. Seeds of foxglove (Digitalis purpurea) in the post-abscission pre-dispersal phase were held at between 15 and 95 % RH for 4 or 8 d, with or without re-hydration to 95 % RH for a further 4 d, before drying to equilibrium at 15 % RH. In addition, dry seeds were primed for 48 h at -1 MPa. Subsequent seed longevity was assessed at 60 % RH and 45 degrees C. Rate of germination and longevity were improved by holding seeds at a wide range of humidities after harvest. Longevity was further improved by re-hydration at 95 % RH. Priming improved the longevity of the seeds dried immediately after harvest, but not of those first held at 95 % RH for 8 d prior to drying. Maturation continued ex planta in these post-abscission, pre-dispersal seeds of D. purpurea dried at 15-80 % RH at a rate correlated positively with RH (cf. ageing of mature seeds). Subsequent re-hydration at 95 % RH enabled a further improvement in quality. Priming seeds initially stored air-dry for 3 months also allowed maturation events to resume. However, once individual seeds within the population had reached maximum longevity, priming had a negative impact on their subsequent survival.

Intergenerational effects of birth weight on glucose tolerance and reproductive performance

Women who were themselves small-for-gestational age (SGA) are at a greater risk of adulthood diseases such as non-insulin-dependent diabetes mellitus (NIDDM), and twice at risk of having an SGA baby themselves. The aim of this study was to examine the intergenerational pig. Low (L) and normal (N) birth weight female piglets were followed throughout their first pregnancy (generation 1 (0)). After they had given birth, the growth and development of the lightest (I) and heaviest (n) female piglet from each litter were monitored until approximately 5 months of age (generation 2 (G2)). A glucose tolerance test (GTT) was conducted on G1 pig at similar to 6 months of age and again during late pregnancy; a GTT was also conducted on G2 pigs at similar to 4 months of age. G1 L offspring exhibited impaired glucose metabolism in later life compared to their G1 N sibling but in the next generation a similar scenario was only observed between I and n offspring born to G1 L mothers. Despite G1 L mothers showing greater glucose intolerance in late pregnancy and a decreased litter size, average piglet birth weight was reduced and there was also a large variation in litter weight; this suggests that they were, to some extent, prioritising their nutrient intake towards themselves rather than promoting their reproductive performance. There were numerous relationships between body shape at birth and glucose curve characteristics in later life, which can, to some extent, be used to predict neonatal outcome. In conclusion, intergenerational effects are partly seen in the pig. It is likely that some of the intergenerational influences may be masked due to the pig being a litter-bearing species.

Caf1A usher possesses a Caf1 subunit-like domain that is crucial for Caf1 fibre secretion

The chaperone/usher pathway controls assembly of fibres of adhesive organelles of Gram-negative bacteria. The final steps of fibre assembly and fibre translocation to the cell surface are co-ordinated by the outer membrane proteins, ushers. Ushers consist of several soluble periplasmic domains and a single transmembrane beta-barrel. Here we report isolation and structural/functional characterization of a novel middle domain of the Caf1A usher from Yersinia pestis. The isolated UMD (usher middle domain) is a highly soluble monomeric protein capable of autonomous folding. A 2.8 angstrom (1 angstrom = 0.1 nm) resolution crystal structure of UMD revealed that this domain has an immunoglobulin-like fold similar to that of donor-strand-complemented Caf1 fibre subunit. Moreover, these proteins displayed significant structural similarity. Although UMD is in the middle of the predicted amphipathic beta-barrel of Caf1A, the usher still assembled in the membrane in the absence of this domain. UMD did not bind Caf1M-Caf1 complexes, but its presence was shown to be essential for Caf1 fibre secretion. The study suggests that UMD may play the role of a subunit-substituting protein (dummy subunit), plugging or priming secretion through the channel in the Caf1A usher. Comparison of isolated UMD with the recent strcture of the corresponding domain of PapC usher revealed high similarity of the core structures, suggesting a universal structural adaptation of FGL (F(1)G(1) long) and FGS (F(1)G(1) short) chaperone/usher pathways for the secretion of different types of fibres. The functional role of two topologically different states of this plug domain suggested by structural and biochemical results is discussed.

Contribution of redox status to hepatitis C virus E2 envelope protein function and antigenicity

Disulfide bonding contributes to the function and antigenicity of many viral envelope glycoproteins. We assessed here its significance for the hepatitis C virus E2 envelope protein and a counterpart deleted for hypervariable region-1 (HVR1). All 18 cysteine residues of the antigens were involved in disulfides. Chemical reduction of up to half of these disulfides was compatible with anti-E2 monoclonal antibody reaction, CD81 receptor binding, and viral entry, whereas complete reduction abrogated these properties. The addition of 5,5'-dithiobis-2-nitrobenzoic acid had no effect on viral entry. Thus, E2 function is only weakly dependent on its redox status, and cell entry does not require redox catalysts, in contrast to a number of enveloped viruses. Because E2 is a major neutralizing antibody target, we examined the effect of disulfide bonding on E2 antigenicity. We show that reduction of three disulfides, as well as deletion of HVR1, improved antibody binding for half of the patient sera tested, whereas it had no effect on the remainder. Small scale immunization of mice with reduced E2 antigens greatly improved serum reactivity with reduced forms of E2 when compared with immunization using native E2, whereas deletion of HVR1 only marginally affected the ability of the serum to bind the redox intermediates. Immunization with reduced E2 also showed an improved neutralizing antibody response, suggesting that potential epitopes are masked on the disulfide-bonded antigen and that mild reduction may increase the breadth of the antibody response. Although E2 function is surprisingly independent of its redox status, its disulfide bonds mask antigenic domains. E2 redox manipulation may contribute to improved vaccine design.

Effect of hyaluronidase on ocular motility and eyelid function in sub-Tenon's anaesthesia: randomised controlled trial

Purpose: To assess the effect of hyaluronidase on eye and eyelid movements when used as an adjunct in sub-Tenon's anaesthesia. Methods: A total of 60 patients who had sub-Tenon's anaesthesia prior to phacoemulsification surgery were divided into two equal groups in a double-masked randomised controlled fashion. Of these, Group A had 4 ml lignocaine 2%, while Group B had 4ml lignocaine 2% with the addition of sodium hyaluronidase 75 IU/ml. Ocular motility, levator, and orbicularis oculi function were measured in all patients at 5 and 8 min. Levator function was scored from 0 (no function) to 3 (complete function) while orbicularis function was scored from 0 to 2. The score for ocular motility was the sum in four positions of gaze, each position scoring from 0 to 2. Results were compared using a nonparametric test. Results Group B achieved significantly better ocular and lid akinesia than Group A both at 5 and 8 min with P < 0.01. The median scores for levator function at 5 and 8 min were 2 for Group A and 0 for Group B. For orbicularis function, the median scores at both time intervals were 2 for Group A and 1 for Group B. For ocular motility, the median score for Group A at 5 min was 3 and at 8 min was 2.5; for Group B at 5 min was 0.5 and at 8 min was 0. Conclusions: The addition of hyaluronidase in sub-Tenon's anaesthesia has a significant effect in improving ocular and lid (levator and orbicularis) akinesia.