Parkinson’s disease (PD) is a neurodegenerative disorder, which is progressive in nature and usually associated with the elderly. It is the second most common age-related neurodegenerative disorder after Alzheimer’s disease (AD). PD occurs when there is a dramatic loss of dopamine (DA) in the striatum, a substructure of the basal ganglia, of the brain due to the degeneration of the nigrostriatal pathway that contains the dopaminergic neurons. Motor symptoms of PD include bradykinesia, muscular rigidity and resting tremors. Non-motor symptoms include speech and sleep problems, hallucinations and depression. Diverse treatment options are available to treat the symptoms of PD, including levodopa (L-Dopa), DA agonists and monoamine oxidase B (MAO-B) inhibitors. The MAOs are flavoproteins that are bound to the outer membrane of the mitochondria and catalyze the oxidative deamination of neurotransmitters such as serotonin (5-HT), noradrenaline (NA) and DA. Two isoforms occur, namely MAO-A and –B, which share a 70% sequence identity. MAO-A catalyzes the oxidation of 5-HT and MAO-B has a substrate specificity towards benzylamine and 2-phenylethylamine. DA, NA, adrenaline and tryptamine are oxidized by both forms. MAO-A plays an important role in depression while MAO-B plays an important role in PD. The two isoforms are not evenly distributed in the brain. Of particular relevance to PD is the observation that, in the basal ganglia, MAO-B is the predominant form and the oxidation of DA in this region is largely due to MAO-B activity. Also, with an increase in age, there is an up to fourfold increase in MAO-B activity in the brain. In the aged parkinsonian brain, MAO-B is therefore a major DA metabolizing enzyme and MAO-B inhibitors have an important role in the therapy of PD. MAO-B inhibitors may potentially reduce the metabolic destruction of DA and thereby provide relief from the symptoms of PD. MAO-B inhibitors may also exert a neuroprotective effect in PD. In the catalytic cycle of MAO-B, one mole each of an aldehyde, hydrogen peroxide and ammonia are formed for each mole of primary amine substrate oxidized. Ferrous iron, which is abundant in the basal ganglia, may react with the hydrogen peroxide to form hydroxyl radicals in the Fenton reaction. The hydroxyl radical damages virtually all types of biomolecules including proteins, DNA, lipids, carbohydrates and amino acids. The aldehyde, in turn, may react with amino groups of proteins, and thus lead to cell injury. Inhibitors of MAO-B may reduce the MAO-catalyzed formation of hydrogen peroxide and aldehydes in the basal ganglia, and thus act as neuroprotective agents. MAO-B inhibitors that are currently being used in the treatment of PD are selegiline and rasagiline. Both are irreversible inhibitors of MAO-B. While irreversible inhibitors of MAO have been used extensively as drugs, irreversible inhibition has a number of disadvantages. These include the loss of selectivity as a result of repeated drug administration and a slow and variable rate of enzyme recovery following termination of drug treatment. The turnover rate for the biosynthesis of MAO-B in the human brain may require as much as 40 days while with reversible inhibition, enzyme activity is recovered when the inhibitor is eliminated from the tissues. For these reasons the discovery of novel MAO-B inhibitors, which interact reversibly with the enzymes are of value in the therapy of PD. The goal of this study was to design novel and reversible inhibitors of MAO-B, which may find application in the therapy of PD. In the current study, caffeine was used as scaffold for the design of new MAO inhibitors. Caffeine is reported to be a weak inhibitor of MAO-B, with an IC50 value of 5084 μM. Substitution at C-8 of the caffeine moiety, however, yields compounds with potent MAO-B inhibitory properties. Of particular importance to this study is a recent report that a series of 8-sulfanylcaffeine analogues acts as selective inhibitors of human MAO-B. Among the compounds examined, 8-[(phenylethyl)sulfanyl]caffeine was found to be a particularly potent MAO-B inhibitor with an IC50 value of 0.223 μM. In an attempt to further enhance the MAO-B inhibition potency of 8-[(phenylethyl)sulfanyl]caffeine, and possibly to discover highly potent MAO-B inhibitors, a series of five 8-[(phenylethyl)sulfanyl]caffeine analogues was synthesized and evaluated as inhibitors of human MAO-A and –B. For the purpose of this study 8- [(phenylethyl)sulfanyl]caffeine homologues containing C-3 alkyl (CF3, CH3 and OCH3) and halogen (Cl and Br) substituents on the phenyl ring were considered. Furthermore, a series of two 8-sulfinylcaffeine analogues and one 8-sulfonylcaffeine were synthesized and their MAO inhibitory potencies were measured. The purpose with these compounds was to compare the MAO inhibitory properties of the 8-sulfinylcaffeine analogues and 8-sulfonylcaffeine with those of the 8-sulfanylcaffeine analogues. This study also investigates the MAO inhibition properties of three selected 8-[(phenylpropyl)sulfanyl]caffeine and two 8-(benzylsulfanyl)caffeine analogues. Chemistry: The target 8-sulfanylcaffeine analogues were synthesized according to the literature procedure. 8-Chlorocaffeine was reacted with an appropriate mercaptan in the presence of NaOH, to yield the target 8-sulfanylcaffeine analogues in yields of 6.4–50.7%. 8-Chlorocaffeine, in turn, was conveniently synthesized in high yield by reacting chlorine with caffeine in chloroform. In certain instances, the mercaptan starting materials were not commercially available and were thus synthesized according to the literature procedure by reacting an appropriate alkylbromide with thiourea. The resulting thiouronium salt was hydrolyzed in the presence of NaOH to yield the target mercaptan. The 8-sulfinylcaffeine analogues and 8- sulfonylcaffeine were synthesized by reacting the 8-sulfanylcaffeines with H2O2 in the presence of glacial acetic acid and acetic anhydride. The structures and the purities of the inhibitors were verified by NMR, MS and HPLC analyses. MAO inhibition studies: The MAO inhibitory properties of the test compounds were examined using the recombinant human enzymes. The mixed MAO-A/B substrate, kynuramine, was employed as substrate for both enzymes and the inhibition potencies were expressed as the IC50 values. The 8-[(phenylethyl)sulfanyl]caffeine analogues were found to be highly potent inhibitors of MAO-B. The IC50 values recorded for these homologues ranged from 0.017–0.125 μM, making them twofold to 13-fold more potent MAO-B inhibitors than the lead compound, 8- [(phenylethyl)sulfanyl]caffeine (IC50 = 0.223 μM). For comparison, the reversible MAO-B selective inhibitor, lazabemide, exhibits an IC50 value of 0.091 μM under the same conditions (unpublished data from our laboratory). Interestingly, both alkyl (CF3, CH3 and OCH3) and halogen (Cl and Br) substitution lead to highly potent MAO-B inhibition. It may therefore be concluded that substitution on C-3 is a general strategy to enhance the MAO-B inhibition potency of 8-[(phenylethyl)sulfanyl]caffeine. The results of the MAO inhibitory studies with the 8- [(phenylpropyl)sulfanyl]caffeine analogues showed that these compounds are also inhibitors of MAO-B with IC50 values of 0.061–0.500 μM. Those homologues substituted with chlorine on the para and meta positions of the phenyl ring were found to be exceptionally potent inhibitors with IC50 values of 0.061 μM and 0.062 μM, respectively. For the series of 8- (benzylsulfanyl)caffeines, meta substitution with chlorine (IC50 = 0.227 μM) and bromine (IC50 = 0.199 μM) was also found to enhance the MAO-B inhibition potency of 8- (benzylsulfanyl)caffeine (IC50 = 1.86 μM). The results document that the 8-sulfinylcaffeines are also inhibitors of MAO-B with IC50 values of 11.8–131 μM. The 8-sulfonylcaffeine was also found to be a MAO-B inhibitor. Compared to the 8-sulfanylcaffeines, these homologues are, however, weaker inhibitors. It may, therefore, be concluded that 8-sulfinylcaffeines and 8-sulfonylcaffeines are comparatively weak MAO-B inhibitors and less suited for the design of high potency MAO-B inhibitors. The results also document that the 8-[(phenylethyl)sulfanyl]caffeines are relatively weak MAO-A inhibitors with IC50 values of 5.66–141 μM, with one homologue exhibiting no inhibition under the experimental conditions. As evident from the selectivity indices (SI values), the 8- [(phenylethyl)sulfanyl]caffeines were all selective inhibitors of the MAO-B isoform. Two compounds exhibited SI values in excess of 1000. Since these compounds are also highly potent MAO-B inhibitors, they represent suitable leads for the design of potent and selective MAO-B inhibitors. The 8-sulfinylcaffeines and 8-sulfonylcaffeine were found to be weak MAO-A inhibitors with IC50 values of 166–250 μM. The SI values demonstrate that these compounds are MAO-B selective inhibitors, although to a lesser degree than the 8- [(phenylethyl)sulfanyl]caffeines. The 8-[(phenylpropyl)sulfanyl]caffeines are also MAO-A inhibitors with IC50 values of 0.708–6.48 μM. It is noteworthy that these homologues are the most potent MAO-A inhibitors among the compounds evaluated in this study. In fact, one of the 8-[(phenylpropyl)sulfanyl]caffeines, 8-{[3-(4-chlorophenyl)propyl]sulfanyl}caffeine (IC50 = 0.708 μM), is the only compound with an IC50 value for the inhibition of MAO-A in the submicromolar range. The 8-[(phenylpropyl)sulfanyl]caffeines display, in general, lower degrees of selectivity for MAO-B than the corresponding 8-[(phenylethyl)sulfanyl]caffeines. Reversibility studies: The reversibility of the interaction of a representative inhibitor, 8-{[2-(3- (trifluoromethyl)phenyl)ethyl]sulfanyl}caffeine, with MAO-B was investigated by evaluating the recovery of the enzymatic activity after dilution of the enzyme-inhibitor complex. For this purpose, MAO-B was preincubated with the test compound at concentrations of 10 × IC50 and 100 × IC50 for 30 min. The reactions were subsequently diluted 100-fold to 0.1 × IC50 and 1 × IC50, respectively. The results show that, after dilution to 0.1 × IC50 and 1 × IC50, the MAO-B catalytic activities are recovered to 35% and 22%, respectively, of the control value. For reversible enzyme inhibition, the enzyme activities are expected to recover to levels of approximately 90% and 50%, respectively, after 100-fold dilution of the preincubations containing inhibitor concentrations of 10 × IC50 and 100 × IC50. After preincubation of MAO-B with the irreversible inhibitor (R)-deprenyl (at 10 × IC50), and dilution of the resulting complex to 0.1 × IC50, MAO-B activity is not recovered (3.0% of control). These data indicate that the test compound does indeed react reversibly with MAO-B but because enzyme activities are not recovered to the expected 90% and 50% respectively, it may suggest that the test compound possess a quasi-reversible or tight-binding component. Hansch-type structure activity relationship studies: A limited Hansch-type QSAR study was performed for the inhibition of MAO by the 8-[(phenylethyl)sulfanyl]caffeines. For this purpose, five parameters were used to describe the physicochemical properties of the C-3 substituents on the phenyl rings of the inhibitors. The Van der Waals volume (Vw) and Taft steric parameter (Es) served as descriptors of the bulkiness of the substituents, while the lipophilicities were described by the Hansch constant (π). The electronic properties were described by the classical Hammett constant (σm) and the Swain-Lupton constant (F). A one-parameter fit with the Taft steric parameter versus the inhibition potency (logIC50) yielded the best correlation with a correlation coefficient (R2) of 0.912 and a statistical F value of 41.27 (Fmax = 35). The positive sign of the Es (+0.47) parameter coefficient indicated that the inhibition potencies of the 8- [(phenylethyl)sulfanyl]caffeines towards MAO-B may be enhanced by substitution with sterically large groups at C-3 of the phenyl rings of the inhibitors. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2013

Parkinson’s disease (PD) is a neurodegenerative disorder, which is progressive in nature and usually associated with the elderly. It is the second most common age-related neurodegenerative disorder after Alzheimer’s disease (AD). PD occurs when there is a dramatic loss of dopamine (DA) in the striatum, a substructure of the basal ganglia, of the brain due to the degeneration of the nigrostriatal pathway that contains the dopaminergic neurons. Motor symptoms of PD include bradykinesia, muscular rigidity and resting tremors. Non-motor symptoms include speech and sleep problems, hallucinations and depression. Diverse treatment options are available to treat the symptoms of PD, including levodopa (L-Dopa), DA agonists and monoamine oxidase B (MAO-B) inhibitors. The MAOs are flavoproteins that are bound to the outer membrane of the mitochondria and catalyze the oxidative deamination of neurotransmitters such as serotonin (5-HT), noradrenaline (NA) and DA. Two isoforms occur, namely MAO-A and –B, which share a 70% sequence identity. MAO-A catalyzes the oxidation of 5-HT and MAO-B has a substrate specificity towards benzylamine and 2-phenylethylamine. DA, NA, adrenaline and tryptamine are oxidized by both forms. MAO-A plays an important role in depression while MAO-B plays an important role in PD. The two isoforms are not evenly distributed in the brain. Of particular relevance to PD is the observation that, in the basal ganglia, MAO-B is the predominant form and the oxidation of DA in this region is largely due to MAO-B activity. Also, with an increase in age, there is an up to fourfold increase in MAO-B activity in the brain. In the aged parkinsonian brain, MAO-B is therefore a major DA metabolizing enzyme and MAO-B inhibitors have an important role in the therapy of PD. MAO-B inhibitors may potentially reduce the metabolic destruction of DA and thereby provide relief from the symptoms of PD. MAO-B inhibitors may also exert a neuroprotective effect in PD. In the catalytic cycle of MAO-B, one mole each of an aldehyde, hydrogen peroxide and ammonia are formed for each mole of primary amine substrate oxidized. Ferrous iron, which is abundant in the basal ganglia, may react with the hydrogen peroxide to form hydroxyl radicals in the Fenton reaction. The hydroxyl radical damages virtually all types of biomolecules including proteins, DNA, lipids, carbohydrates and amino acids. The aldehyde, in turn, may react with amino groups of proteins, and thus lead to cell injury. Inhibitors of MAO-B may reduce the MAO-catalyzed formation of hydrogen peroxide and aldehydes in the basal ganglia, and thus act as neuroprotective agents. MAO-B inhibitors that are currently being used in the treatment of PD are selegiline and rasagiline. Both are irreversible inhibitors of MAO-B. While irreversible inhibitors of MAO have been used extensively as drugs, irreversible inhibition has a number of disadvantages. These include the loss of selectivity as a result of repeated drug administration and a slow and variable rate of enzyme recovery following termination of drug treatment. The turnover rate for the biosynthesis of MAO-B in the human brain may require as much as 40 days while with reversible inhibition, enzyme activity is recovered when the inhibitor is eliminated from the tissues. For these reasons the discovery of novel MAO-B inhibitors, which interact reversibly with the enzymes are of value in the therapy of PD. The goal of this study was to design novel and reversible inhibitors of MAO-B, which may find application in the therapy of PD. In the current study, caffeine was used as scaffold for the design of new MAO inhibitors. Caffeine is reported to be a weak inhibitor of MAO-B, with an IC50 value of 5084 μM. Substitution at C-8 of the caffeine moiety, however, yields compounds with potent MAO-B inhibitory properties. Of particular importance to this study is a recent report that a series of 8-sulfanylcaffeine analogues acts as selective inhibitors of human MAO-B. Among the compounds examined, 8-[(phenylethyl)sulfanyl]caffeine was found to be a particularly potent MAO-B inhibitor with an IC50 value of 0.223 μM. In an attempt to further enhance the MAO-B inhibition potency of 8-[(phenylethyl)sulfanyl]caffeine, and possibly to discover highly potent MAO-B inhibitors, a series of five 8-[(phenylethyl)sulfanyl]caffeine analogues was synthesized and evaluated as inhibitors of human MAO-A and –B. For the purpose of this study 8- [(phenylethyl)sulfanyl]caffeine homologues containing C-3 alkyl (CF3, CH3 and OCH3) and halogen (Cl and Br) substituents on the phenyl ring were considered. Furthermore, a series of two 8-sulfinylcaffeine analogues and one 8-sulfonylcaffeine were synthesized and their MAO inhibitory potencies were measured. The purpose with these compounds was to compare the MAO inhibitory properties of the 8-sulfinylcaffeine analogues and 8-sulfonylcaffeine with those of the 8-sulfanylcaffeine analogues. This study also investigates the MAO inhibition properties of three selected 8-[(phenylpropyl)sulfanyl]caffeine and two 8-(benzylsulfanyl)caffeine analogues. Chemistry: The target 8-sulfanylcaffeine analogues were synthesized according to the literature procedure. 8-Chlorocaffeine was reacted with an appropriate mercaptan in the presence of NaOH, to yield the target 8-sulfanylcaffeine analogues in yields of 6.4–50.7%. 8-Chlorocaffeine, in turn, was conveniently synthesized in high yield by reacting chlorine with caffeine in chloroform. In certain instances, the mercaptan starting materials were not commercially available and were thus synthesized according to the literature procedure by reacting an appropriate alkylbromide with thiourea. The resulting thiouronium salt was hydrolyzed in the presence of NaOH to yield the target mercaptan. The 8-sulfinylcaffeine analogues and 8- sulfonylcaffeine were synthesized by reacting the 8-sulfanylcaffeines with H2O2 in the presence of glacial acetic acid and acetic anhydride. The structures and the purities of the inhibitors were verified by NMR, MS and HPLC analyses. MAO inhibition studies: The MAO inhibitory properties of the test compounds were examined using the recombinant human enzymes. The mixed MAO-A/B substrate, kynuramine, was employed as substrate for both enzymes and the inhibition potencies were expressed as the IC50 values. The 8-[(phenylethyl)sulfanyl]caffeine analogues were found to be highly potent inhibitors of MAO-B. The IC50 values recorded for these homologues ranged from 0.017–0.125 μM, making them twofold to 13-fold more potent MAO-B inhibitors than the lead compound, 8- [(phenylethyl)sulfanyl]caffeine (IC50 = 0.223 μM). For comparison, the reversible MAO-B selective inhibitor, lazabemide, exhibits an IC50 value of 0.091 μM under the same conditions (unpublished data from our laboratory). Interestingly, both alkyl (CF3, CH3 and OCH3) and halogen (Cl and Br) substitution lead to highly potent MAO-B inhibition. It may therefore be concluded that substitution on C-3 is a general strategy to enhance the MAO-B inhibition potency of 8-[(phenylethyl)sulfanyl]caffeine. The results of the MAO inhibitory studies with the 8- [(phenylpropyl)sulfanyl]caffeine analogues showed that these compounds are also inhibitors of MAO-B with IC50 values of 0.061–0.500 μM. Those homologues substituted with chlorine on the para and meta positions of the phenyl ring were found to be exceptionally potent inhibitors with IC50 values of 0.061 μM and 0.062 μM, respectively. For the series of 8- (benzylsulfanyl)caffeines, meta substitution with chlorine (IC50 = 0.227 μM) and bromine (IC50 = 0.199 μM) was also found to enhance the MAO-B inhibition potency of 8- (benzylsulfanyl)caffeine (IC50 = 1.86 μM). The results document that the 8-sulfinylcaffeines are also inhibitors of MAO-B with IC50 values of 11.8–131 μM. The 8-sulfonylcaffeine was also found to be a MAO-B inhibitor. Compared to the 8-sulfanylcaffeines, these homologues are, however, weaker inhibitors. It may, therefore, be concluded that 8-sulfinylcaffeines and 8-sulfonylcaffeines are comparatively weak MAO-B inhibitors and less suited for the design of high potency MAO-B inhibitors. The results also document that the 8-[(phenylethyl)sulfanyl]caffeines are relatively weak MAO-A inhibitors with IC50 values of 5.66–141 μM, with one homologue exhibiting no inhibition under the experimental conditions. As evident from the selectivity indices (SI values), the 8- [(phenylethyl)sulfanyl]caffeines were all selective inhibitors of the MAO-B isoform. Two compounds exhibited SI values in excess of 1000. Since these compounds are also highly potent MAO-B inhibitors, they represent suitable leads for the design of potent and selective MAO-B inhibitors. The 8-sulfinylcaffeines and 8-sulfonylcaffeine were found to be weak MAO-A inhibitors with IC50 values of 166–250 μM. The SI values demonstrate that these compounds are MAO-B selective inhibitors, although to a lesser degree than the 8- [(phenylethyl)sulfanyl]caffeines. The 8-[(phenylpropyl)sulfanyl]caffeines are also MAO-A inhibitors with IC50 values of 0.708–6.48 μM. It is noteworthy that these homologues are the most potent MAO-A inhibitors among the compounds evaluated in this study. In fact, one of the 8-[(phenylpropyl)sulfanyl]caffeines, 8-{[3-(4-chlorophenyl)propyl]sulfanyl}caffeine (IC50 = 0.708 μM), is the only compound with an IC50 value for the inhibition of MAO-A in the submicromolar range. The 8-[(phenylpropyl)sulfanyl]caffeines display, in general, lower degrees of selectivity for MAO-B than the corresponding 8-[(phenylethyl)sulfanyl]caffeines. Reversibility studies: The reversibility of the interaction of a representative inhibitor, 8-{[2-(3- (trifluoromethyl)phenyl)ethyl]sulfanyl}caffeine, with MAO-B was investigated by evaluating the recovery of the enzymatic activity after dilution of the enzyme-inhibitor complex. For this purpose, MAO-B was preincubated with the test compound at concentrations of 10 × IC50 and 100 × IC50 for 30 min. The reactions were subsequently diluted 100-fold to 0.1 × IC50 and 1 × IC50, respectively. The results show that, after dilution to 0.1 × IC50 and 1 × IC50, the MAO-B catalytic activities are recovered to 35% and 22%, respectively, of the control value. For reversible enzyme inhibition, the enzyme activities are expected to recover to levels of approximately 90% and 50%, respectively, after 100-fold dilution of the preincubations containing inhibitor concentrations of 10 × IC50 and 100 × IC50. After preincubation of MAO-B with the irreversible inhibitor (R)-deprenyl (at 10 × IC50), and dilution of the resulting complex to 0.1 × IC50, MAO-B activity is not recovered (3.0% of control). These data indicate that the test compound does indeed react reversibly with MAO-B but because enzyme activities are not recovered to the expected 90% and 50% respectively, it may suggest that the test compound possess a quasi-reversible or tight-binding component. Hansch-type structure activity relationship studies: A limited Hansch-type QSAR study was performed for the inhibition of MAO by the 8-[(phenylethyl)sulfanyl]caffeines. For this purpose, five parameters were used to describe the physicochemical properties of the C-3 substituents on the phenyl rings of the inhibitors. The Van der Waals volume (Vw) and Taft steric parameter (Es) served as descriptors of the bulkiness of the substituents, while the lipophilicities were described by the Hansch constant (π). The electronic properties were described by the classical Hammett constant (σm) and the Swain-Lupton constant (F). A one-parameter fit with the Taft steric parameter versus the inhibition potency (logIC50) yielded the best correlation with a correlation coefficient (R2) of 0.912 and a statistical F value of 41.27 (Fmax = 35). The positive sign of the Es (+0.47) parameter coefficient indicated that the inhibition potencies of the 8- [(phenylethyl)sulfanyl]caffeines towards MAO-B may be enhanced by substitution with sterically large groups at C-3 of the phenyl rings of the inhibitors. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2013

La literatura de la migración latinoamericana no ha despertado interés académico en el hispanismo europeo hasta hace bien poco. Este estudio se interesa precisamente por esta cuestión desde una perspectiva de género –en el sentido anglosajón de gender–. Éste se entiende como actitud performativa que crea normas y modelos pero también seres a-normativos y cuerpos inclasificables por lo que se estudiarán las políticas de representación de estos cuerpos y subjetividades migrantes. Tres obras de ficción de finales del siglo XX y principios del siglo XXI serán analizadas: El camino a Ítaca (1994), del escritor uruguayo-europeo Carlos Liscano; Árbol de luna (2000), del venezolano madrileño Juan Carlos Méndez Guédez y The Brief Wondrous Life of Oscar Wao (2008), del dominicano expatriado Junot Díaz. A partir de este corpus de textos de autores masculinos, estudiaré la manera en que el registro de la subjetividad en materia de género viene a combinarse con otros “datos identitarios” como las diferencias de clase, raza, etnia y la pertenencia nacional. Además, se intentará analizar el proceso de re-subjetivación individual y colectiva que el discurso literario marca a partir de un protocolo de representación en el que la dimensión sexual y de género resultan ser definitorias. La cuestión del género se plantea pues en términos de posibilidades estéticas discursivas en el marco de recorridos migratorios literarios variados. Tras un capítulo de índole epistemológica, sitúo las tres novelas analizadas en el panorama de las manifestaciones discursivas de las oleadas migratorias latinoamericanas en relación con los debates que surgieron acerca de la literatura migrante en las áreas francófonas, anglosajonas e hispánicas. En este ámbito, se destacarán algunas de las numerosas cuestiones que suscita la definición de la literatura de la migración latinoamericana intentándose circunscribir este campo de estudio. Dedicados al análisis textual como tal, los capítulos siguientes se centrarán en primer lugar en la novela Árbol de luna de Juan Carlos Méndez Guédez, a partir de la polisemia del concepto de tópico de género (como género literario y gender) y de etos discursivo. En segundo lugar, abordaré la novela The Brief Wondrous Life of Oscar Wao del escritor Junot Díaz a través de un estudio de la “corpo-grafía”, es decir el análisis de la escritura y representación de esos cuerpos no reconocidos situados en enunciados culturales diferentes. Me interesaré especialmente en la estrategia de enderezamiento del narrador que, por medio de su relato y estilo discursivo, impone su propia encarnación normativa de la masculinidad de la diáspora dominicano-americana. Finalmente, en el marco del estudio de la novela El camino a Ítaca de Carlos Liscano, exploraré cómo el concepto de “heterotopía” propuesto por M. Foucault permite entender la migración del personaje principal de la obra, Vladimir, en paralelo con la reformulación de su masculinidad. Asimismo, se examinará el estilo y los géneros literarios manejados por este narrador para dar cuenta de su viaje distópico. / Cette étude s’intéresse à la question de la littérature de la migration latino-américaine – une thématique qui n’a éveillé un intérêt que très récemment dans l’hispanisme européen – à partir d’une perspective de genre. Étant donné que le déplacement géographique impose un questionnement des normes culturelles, spécialement celles relatives au genre, on étudie ici les politiques de représentation de ces corps et de ces subjectivités migrantes dans trois œuvres de fiction de la fin du vingtième et du début du vingt et unième siècle à savoir El camino a Ítaca (1994), de l’auteur uruguayen-européen Carlos Liscano; Árbol de luna (2000), du vénésuelo-madrilène Juan Carlos Méndez Guédez, et The Brief Wondrous Life of Oscar Wao (2008), du dominicain-américain Junot Díaz. A partir de ce corpus de textes d’auteurs masculins, on étudie la manière dont le registre de la subjectivité en matière de genre vient se combiner avec d’autres « données identitaires » comme les différences de classe, de race, d’ethnie et d’appartenance nationale. Il s’agit également d’analyser le processus de re-subjectivation individuelle et collective que le discours littéraire vient marquer d’un protocole de représentation où la dimension sexuelle s’avère définitoire. La question du genre est donc abordée en termes de possibilités esthétiques discursives et se comprend dans le cadre de parcours migratoires fictionnels très différents. Après un chapitre de nature épistémologique, les romans sont situés dans le panorama des manifestations discursives des vagues migratoires latino-américaines en lien avec les débats qui ont surgi à propos de la littérature migrante dans le domaine francophone, anglo-saxon et finalement hispanique. Dans ce cadre, on souligne certaines des nombreuses questions que suscite la définition de la littérature de la migration latino-américaine tout en tentant de circonscrire ce champ d’étude. Les chapitres suivants, dédiés à l’analyse textuelle en tant que telle, se centrent, dans un premier temps, sur le roman Árbol de luna de J. C. Méndez Guédez à partir de la notion d’éthos discursif et de la polysémie du concept de topique – dans le cadre des genres littéraires et du genre social. Dans un second temps, l’analyse se focalise sur The Brief Wondrous Life of Oscar Wao de Junot Díaz à travers l’étude de la « corpo-graphie », c'est-à-dire de l’écriture et de la représentation des corps non-reconnus situés entre deux normes culturelles. L’analyse porte spécialement sur la stratégie de « rectification » du narrateur qui, au moyen de divers procédés discursifs, impose son propre modèle normatif de masculinité de la diaspora dominicaine-américaine. Finalement, dans le cadre de l’étude du roman El camino a Ítaca de Carlos Liscano, il s’agit d’explorer comment le concept d’hétérotopie proposé par M. Foucault permet de comprendre la migration du personnage principal de l’œuvre, Vladimir, en parallèle avec la reformulation de sa masculinité. De plus, il s’agit d’examiner le style et les genres littéraires convoqués par ce narrateur pour rendre compte de son voyage distopique. / Latin American migration literature is only recently a subject of study in European academies; the present thesis addresses this by dealing with the subject from a gender perspective. The gender question, understood as a performative attitude which creates norms and models but also a-normative beings and uncategorisable bodies, is at the centre of this work which, more specifically, brings into focus the politics of representation of those bodies and migrant subjectivities. Three works of narrative fiction from the end of the twentieth century and beginning of the twenty-first are here analyzed: El camino a Ítaca (1994), by Uruguayan-European author Carlos Liscano; Árbol de Luna (2000), by Venezuelan and now Madrid adoptive Juan Carlos Méndez Guédez; and The Brief Wondrous Life of Oscar Wao (2008), by Domincan-American writer J. Díaz. Basing myself on that body of novels by male writers, I examine the way the subjectivity of gender-oriented register is combined with other “identity data” as class, race, ethnic differences and nationality. Moreover, this study focuses on the individual and collective re-subjectification process that the literary discourse transcribes through representation conventions in which the sexual and gender dimension is determining. The gender question is, therefore, discussed in terms of discursive aesthetic possibilities and is analysed in the particular cases of various literary migratory itineraries. Following an explanation of this study’s epistemology, the place of the three novels within the context of discursive manifestations of contemporary Latin American migration is discussed in relation to debates over migrant literature that have arisen in the French-speaking, English-speaking and Spanish-speaking areas. As part of that endeavour, I highlight some of the many questions that Latin American migration literature raises in attempting to delimit that corpus of study. Next there follows a literary analysis which focuses firstly on the novel Árbol de luna by J. C. Méndez Guédez through a new understanding of the notion of “discursive ethos” and considering “stereotype” in its polysemic capacity – as it may be used in both gender and literary genre. Secondly, I focus on “corpo-grafía”, i. e. an analysis of the writing process and representation of an unrecognized body situated in different cultural conceptions as it appears in Junot Díaz’s novel The Brief Wondrous Life of Oscar Wao. What is especially emphasized is the narrator’s “straightening strategy” which imposes the latter’s personal normative embodiment of the Dominican-American Diaspora masculinity by way of its narrative and unique discursive style. Finally, I explore the way in which the concept of “heterotopy” proposed by M. Foucault facilitates one’s approach to Vladimir, the protagonist of C. Liscano’s El camino a Ítaca. The style and literary genres employed to inform the reader about that dystopian travel are also addressed.

Esta investigación tiene como propuesta analizar las obras dramáticas La casa de Bernarda Alba, de Federico García Lorca (1898–1936) y Dorotéia, del brasileño Nelson Rodrigues (1912-1980), desde el marco de la literatura comparada. Se ha buscado elucidar no tanto los elementos visibles y explícitos que pueden aproximan ambos textos, sino desentrañar más el aspecto simbólico, implícito y mítico que conllevan en su interior. Como uno de los objetivos de este trabajo es hacer un análisis mitopoético, el primer capítulo inicia con algunas reflexiones sobre el concepto de mito. En la búsqueda por crear un campo de diálogo entre los relatos míticos con el corpus literario matriz de esta investigación, la segunda parte de este capítulo está dedicada a las imágenes bajo el enfoque de la psicología arquetípica, de donde se ha extraído el concepto de lo “imaginal” que apunta el modus operandi de este ensayo. Como el tipo de análisis propuesto se inserta en el ámbito mitopoético, el segundo capítulo aproxima los dos textos modernos a los relatos mítico de Psique y Perséfone. Estos dos personajes femeninos bajan al reino del inframundo, donde logran un crecimiento interior, lo que se asemeja a los procesos psíquicos vividos por los personajes principales de las obras que elegimos para esta investigación. Este capítulo, también aborda el género dramático y el teatro de Nelson Rodrigues y García Lorca, autores de las obras que consagramos para este ensayo. El tercer capítulo desarrolla un ejercicio de comparación entre Dorotéia y La casa de Bernarda Alba: primero, se aborda lo femenino y la familia como temas arquetípicos; luego, el hogar, la religión y la sexualidad como temas circundantes; y, finalmente, se aproximan las historias de Dorotéia y Psique y de La casa de Bernarda Alba y Perséfone. El último capítulo se compone de dos apartados: uno trata de los sentimientos inferiores y otro de las imágenes “almadas” de las obras –medios utilizados para acceder a la realidad psíquica de los personajes. Debido a la importancia dada a la imagen en este trabajo, hemos seleccionado unas fotografías de montajes de Dorotéia y La casa de Bernarda Alba, relacionándolas con las cuestiones que hemos tratado en los dos últimos capítulos de esta tesis, imágenes que se reproducen en el anexo de esta tesis. / The intention of this research is to analyse the dramatic texts La casa de Bernarda Alba by Federico García Lorca (1898-1936) and Dorotéia by the Brazilian Nelson Rodrigues (1912-1980) from the comparative literature framework. It has been seek not just to clarify the visible and explicit element that approximate both texts but to develop the symbolic, implicit and mythic aspect the carry within. As the aim of this work is to do a mythopoetic analysis, the first chapter starts with some reflections about the concept of myth. With the intention of creating a dialogue field between the mythic tales and the literary corpus matrix of this investigation, the second part of this chapter is dedicated to the images under the focus of the arquetipic psychology, from where it was extracted the concept of ¨imaginal¨ which points to the modus operandi of this essay. As the type of analysis suggested is inserted in the mythopoetic area, the second chapter approximates the two modern texts to the mythic tales of Psyque and Persephone. Both feminine characters go down into the underworld kingdom, where they achieve an inner growth, similar to the psyquic process experienced by the main characters of the two dramas chosen in this investigation. This chapter, approaches the dramatic genre and the dramatic works of Nelson Rodrigues and García Lorca, authors of the two dramas studied in this thesis. The third chapter develops a comparison exercise between Dorotéia and La casa de Bernarda Alba: firstly the concept of feminine and family are studied as arquetipic issues; secondly the home, religion and sexuality are studied as surrounding issues; and finally, there is an approximation of the stories of Dorotéia and Psyque and La casa de Bernarda Alba and Persephone. The last chapter is composed by two sections: one talks about the feelings of inferiority and the other about the ¨souled¨ images –means used to access the psyquic reality of the characters. According to the importance give to the images in this work, there have been selected some fotographs from the plays on stage of Dorotéia and La casa de Bernarda Alba, related to the issues treated in the last two chapters of the thesis, the mentioned images are attached to the end of this work.

Bacterial isolates from animals, foods and clinical samples with resistances to one or more antibiotics are being found frequently each year. Selective pressure exerted by antibiotic growth promoters in food animals has been considered a main cause for the development of antibiotic resistance and antibiotic use has been strongly criticized as a serious public health threat. The gastrointestinal tract of animals not only serves as a reservoir of zoonotic agents but also as a spot for exchange of genetic information between pathogenic and commensal bacteria. Humans get infections from resistant bacteria either through the food chain, contaminated water or by direct contact with animals. In this situation much of the concern has been directed against the use of antibiotic growth promoters in animals. The removal of synthetic antibiotics from animal diets created other problems such as a decline in animal welfare and an increase in the use of therapeutic antibiotics. So there is a need for new alternatives to antimicrobial drugs to overcome resistance development and related problems. Plants and plant-derived compounds have long been considered to posess antimicrobial activity since they were frequently used in ancient medicine as natural remedies to treat human infections. Identifying new sources of natural antimicrobials and inhibitors of resistance development will yield novel therapeutic drugs and extend the useful life of existing antibiotics. In the present work, individual and combined effects of five essential oils (eugenol, thymol, carvacrol, cinnamaldehyde, allyl isothiocyanate (AIT)) and a formaldehyde-based feed additive, Termin 8, with antibiotics against 4 antibiotic resistant bacteria with known determinants for resistance were tested using broth microdilution and the checker board assay. The bacteria showed considerable susceptibility towards these antimicrobials and a significant reduction in the minimum inhibitory concentrations (MICs) of antibiotics was noted when paired combinations of antibiotic and antimicrobial were used. The synergistic interaction was further confirmed by the extent of decrease in logarithmic count or viable population (Log DP). Although most of the combinations were synergistic by fractional inhibitory concentration (FIC) values, fewer combinations showed synergistic interaction when Log DP was considered. Gram-positive bacteria were more sensitive to the antimicrobials than Gram-negative bacteria. In combination studies, carvacrol was more effective and showed synergistic interaction with at least three antibiotics. When used alone, AIT was more effective and the concentration needed to exhibit antimicrobial action was much lower when compared to other compounds. An in vitro study was conducted to assess the antibacterial effects of Termin 8 and thymol in chicken caecal digesta and poultry feed samples by using a thin agar layer (TAL) method. Concentrations greater than the MIC of both the compounds was required to exert antimicrobial activity in the feed and digesta samples. The natural antimicrobials and Termin 8 had significant inhibitory effects on the drug resistant bacteria and synergistically enhanced the efficacy of antibiotics when used in combination. Further studies are needed to test their effectiveness in animal models.

El Regiment dels prínceps, de Gil de Roma, no ha estat mai gaire estudiat. Nosaltres afrontem l’edició textual de la traducció catalana del Regiment dels prínceps, del segle XIV, de notable tradició i que gaudí de gran difusió en el nostre entorn. Sobre el traductor del text al català, Arnau Estanyol, creiem que aquesta vegada en clarificarem l’adscripció, tant en el temps com en l’espai, sense deixar-lo en la mera referència al manuscrit de l’Escorial. Estanyol fou un religiós carmelità amb una bona formació, que passà el temps entre l’Estudi Generals de Girona i el de Lleida. Un home que a més tingué la cultura suficient per abordar un text difícil i aclarir algunes qüestions de vocabulari difícil a l’època en la seva famosa Explanació d’alguns vocables obscurs. Sobre els manuscrits, tres han arribat a l’actualitat, hem fet una bona descripció i un treball profund de filiació i datació, quedant clara la importància del text. El text ha estat editat seguint tots el criteris moderns d’edició, puntuació i ortografia, tot respectant les característiques d’un text de la seva època i seguint les normes de Els Nostres Clàssic i de l’IEC. El Regiment dels prínceps va ser escrit amb la intenció d’educar el fill de Felip III, dit l’Ardit, Felip, futur rei de França, dit el Bell, per d’ensenyar els principis elementals de l’època: la monàstica, l’economia i la política. Gil de Roma s’acosta a coses que sorprenen, fent discursos sobre el caràcter del príncep aprofundint en la psicologia humana. El Regiment aborda un tema fonamental, que és el poder del rei, per a Gil de Roma no està deslligat de la seva essència divina. Quin és el poder per sobre del poder? El rei, el Papa? Gil de Roma no enfronta aquests dos poders; tots els poders es reconeixen en un sol agent, que és Déu; una idea que, com sabem, també va prendre Francesc Eiximenis. Gil de Roma té una dimensió humana que no és fàcil de trobar en el món medieval, i tampoc en ell mateix, que en altres obres no és gens compassiu ni caritatiu envers el sexe contrari. No el podríem catalogar de «feminista», ni de bon tros –sap molt bé quin és el paper de cadascú en la seva societat–, però si que té una perspectiva diferent quant a l’educació dels qui són a prop del príncep. De vegades l’autor ens aproxima a les teories sofistes, que tan ressò tenen en la psicologia del caràcter actual. Parla d’Al-Farabi, i ens preguntem si l’erudit no devia conèixer més que no pensem aquesta filosofia, la psicologia del caràcter. Què fascinà Jaume d’Urgell i altres prínceps del seu temps per què aquesta obra tingués tanta difusió? Probablement el títol mateix –un regiment de prínceps devia captivar tota la noblesa de l’època. / The Regiment of Princes, Giles of Rome has never been much studied. We are facing the Catalan edition of the textual translation of the Regiment of Princes, from the fourteenth century; this text has a remarkable tradition and was an important dissemination in our environment About the translator of the text in Catalan, Arnau Estanyol, we think that now we can clarify his born place and when he was born. Estanyol was a Carmelite nuns with a good academic training, he spend his time between “l’Estudi General” (university) from Girona and from Lleida. This man who had enough culture for deal with any difficult text and he could clarify some questions of difficult vocabulary in his famous “Explanació d’alguns vocables obscurs”. Nowadays it has arrived three manuscripts to us, we have had a good description and an affiliation and datation very deep work, it been made clear the importance of text. This text has been edited followed all the edition moderns criterias and it follows the rules of “Els Nostres Clàssics” and the IEC. The Regiment of Princes was writing with the intended to educate the Philip III of France’s son, Philip of Bell, and for to teach the time elementals principles: the monastic, the economic and the politic. Giles of Rome approaches to surprising things, he made speeches about the price character and to the human psychology. The Regiment tackles a fundamental subject: the king power. For Giles of Rome it isn’t exempt from the divine essence. Which is the power over the power? The king? The Poppe? Giles of Rome doesn’t bring face to face this two powers; all the powers are recognising in one only agent which is God; one idea, how we know, it took Francesc Eiximenis. Giles of Rome has an human dimension it isn’t easy to find in the medieval world, nor in itself, because in another works isn’t nothing merciful and charitable with the opposite sex. It can’t be catalogued as “feminist” -he knows very well which the each one role in the society is-, but it’s true that he have a different perspective respect to the people close to the price. Sometimes the author approaches us to the Sufism theory, that it has so much echo in the nowadays character psychology. It talk about Al-Farabi, and we wonder if the erudite mustn’t to know to much we know about this philosophy: the character psychology. What fascinate to Jaume d’Urgell and other contemporary princes so that this work had so many diffusion? Probably the title itself - a regiment of princes would captivate all the time nobility.

Esta tesis doctoral explora la recepción de los personajes audiodescritos por parte de usuarios ciegos o con baja visión (CocBV). Para ello, parte de un cuerpo teórico en dos bloques, uno sobre memoria humana y otro sobre recepción de personajes de ficción, que sustentan una investigación empírica en forma de estudio de recepción. El bloque sobre memoria humana se ocupa de analizar los procesos que tienen lugar en la mente del receptor para comprender los productos fílmicos. Los esquemas mentales, estructuras de conocimiento del mundo que adquirimos a lo largo de nuestra experiencia vital, nos permiten interpretar la información que recibimos a través de la pantalla y crear un modelo mental de la situación expuesta en un proceso conjunto entre la memoria a largo plazo y la memoria de trabajo. Ahora bien, esta última tiene capacidades limitadas, lo cual podría tener ciertas implicaciones para la audiodescripción (AD). Investigaciones de los ámbitos de la percepción, la memoria, los medios de comunicación y la educación parecen indicar que la información visual o combinaciones entre visual y acústica se recuerdan mejor que la que se transmite solo en formato acústico. Además, la información verbal que se incluye en la AD se presenta fragmentada en aquellas partes de la película donde no hay sonidos relevantes. Ambas cosas podrían sugerir que los receptores CocBV han de realizar un esfuerzo cognitivo mayor para comprender una película que los espectadores videntes, quienes reciben la información a través de dos canales (visual y acústico) y tienen acceso a la narrativa fílmica de forma continua e inmediata. Con todo, se suele considerar que las personas CocBV tienen mejor memoria para materiales verbales recibidos a través del canal acústico que los videntes y esto, quizá, podría compensar ese mayor esfuerzo cognitivo. Sin embargo, los estudios realizados en el campo de la psicología cognitiva que han evaluado esta hipótesis no son concluyentes. Esta tesis se propone analizar las implicaciones de estas ideas en el caso concreto de la recepción de los personajes audiodescritos. Para estudiar la recepción de los personajes de ficción nos basamos en la narratología cognitiva, que explora los procesos que tienen lugar en la mente del receptor de narrativas. Puesto que no existe ninguna teoría que describa la recepción de los personajes audiodescritos, partimos de la de Schneider (2001) para personajes literarios y la aplicamos a la AD. De acuerdo con el autor, puesto que los personajes son elementos clave de la narrativa, los lectores crean representaciones mentales de ellos al construir los modelos de la situación ficticia y, según nuestra hipótesis, este argumento sería válido también para los receptores de productos cinematográficos y, por extensión, para los destinatarios de productos audiodescritos. Dicho proceso de (re)construcción de los personajes es dinámico y se lleva a cabo gracias a la memoria. Sin embargo, puesto que la memoria de trabajo es limitada, las representaciones mentales de los personajes son inevitablemente incompletas. A partir de este repaso teórico, la presente tesis doctoral analiza empíricamente cómo las limitaciones de la memoria afectan a la recepción de los personajes mediante un estudio de recepción realizado con cuarenta y cuatro personas CocBV. En concreto, estudiamos cómo la cantidad de la información que se incluye en la AD y su segmentación afectan al recuerdo de los receptores. Los resultados de nuestras pruebas indican que las descripciones con pocos detalles y las AD que se presentan segmentadas favorecen el recuerdo de los usuarios. / This doctoral dissertation explores the reception of audio described characters by blind and visually impaired (BVI) audiences. It departs from a theoretical framework combining insights from human memory and character reception, which leads to an empirical research in the form of a reception study. The theoretical framework investigating human memory analyzes the mental processes that spectators undertake in order to comprehend movies. Mental schemata, structures that contain the knowledge of the world acquired throughout life, allow them to interpret the information that they receive through the screen. Concurrently, they enhance the creation of a mental model of the fictional situation in a joint process involving long term memory and working memory. However, the latter is capacity-limited, which could have some implications for audio description (AD). Research within the fields of Perception, Memory, Media and Education Studies seem to suggest that visual information or combinations of visual and auditory information tend to be recalled more effectively than auditory information alone. Furthermore, the verbal information contained in the AD is usually fragmented and delivered in those parts of the film in which no relevant sound or dialogue are heard. These could indicate that BVI users might need more cognitive effort to comprehend audio described movies than sighted viewers, who receive the information through two channels (visual and auditory), and who access the filmic narrative in a continuous and immediate manner. On the other hand, the BVI are believed to have a better memory for verbal materials presented auditorily and this could, perhaps, neutralize that extra effort. However, research exploring this hypothesis in the field of Cognitive Psychology has proven inconclusive. It is the aim of this thesis to analyze the implications of the aforementioned ideas in the specific case of the reception of audio described characters. In order to study the reception of fiction characters, the focus will be placed on Cognitive Narratology, a discipline aimed at exploring the mental processes that take place in the mind of the narrative recipients. Since those processes have not been described for BVI audiences, Schneider’s reception theory of literary characters will first be explored and will then be applied to AD. According to the author, characters are key figures within narratives and, as such, readers create mental representations of them in their attempt to mentally represent the fictional situation. It is our belief that this argument could generalize to film characters and, by extension, also to characters in audio described films. The process of (re)creating characters is dynamic and it is performed by our memory. Nevertheless, due to working memory capacity limitations, the mental representations of characters are inevitably incomplete. This theoretical review leads to an empirical analysis of how memory limitations affect the reception of audio described film characters. Specifically, a reception study was carried out with forty-four BVI participants to explore how the amount of information included in the AD and its segmentation affected users’ recall. The results obtained showed that limiting the information in the descriptions and dividing it into short units delivered at different stages of the AD favored users’ memory.

la presente tesis pretende estudiar el concepto de la virtualidad, sus poéticas, su estética, su estilo y sus modalidades. En una sociedad en que predominan los ideales de inmersión, presencia e interactividad, la virtualidad se convierte en un «estilo posmoderno intermediático» donde la noción de lo virtual es un elemento temático integrado en una estética cuya principal articulación es la oposición de lo virtual a lo real. Los procesos de virtualización que se operan en nuestras vidas cotidianas apoyados por el avance de la tecnología digital traducen no sólo una bifurcación de lo real en un conjunto de «posibles», sino también la «creación» o «actualización» de un real nuevo, autónomo, capaz de producir «simulacros» y «espectros» de lo real. Como herramienta que revoluciona las estrategias de creación artística y modifica nuestra manera de simbolizar y aprehender lo real, la virtualidad «amplía» el campo de acción de la ficción en un momento en que se acentúa la tendencia a la sofisticación de los productos de la imaginación. La emergencia de una literatura y de un cine que han hecho de lo virtual el modo idóneo para generar lo ficticio, lo plural, lo posible y lo híbrido se manifiesta cada vez más en la capacidad que ofrece el texto literario y la imagen cinematográfica de transportar al lector y al espectador a un territorio virtual, accesible, manejable, inmersivo e interactivo, a un mundo posible situado entre lo utópico y lo distópico, lo verdadero y lo falso, lo real y lo ilusorio, en fin, a una «realidad virtual». / The present thesis aims to study the concept of virtuality, its poetics, aesthetics, style and its modes. In a society where the ideals of immersion, presence and interactivity predominate, virtuality has become a «cross-media postmodern style» where the notion of the virtual is a thematic element integrated in aesthetics whose primary articulation is the opposition from the virtual to the real. The processes of virtualization taking place in our everyday lives supported by the advance of digital technology not only translate a bifurcation of reality into a set of «possible» but also the «creation» or «update» of a new real, autonomous, capable of producing «simulacra» and «specters» of the real. As a tool which revolutionizes the strategies of artistic creation and changes our way of symbolizing and apprehending the real, virtuality broadens the scope of action of the fiction in a moment when the trend is emphasized to the sophistication of the products of the imagination. The emergence of a literature and a cinema, which have made the virtual an ideal mode to generate the fictitious, the plural, the possible and the hybrid, is manifested increasingly in the capacity offered by the literary text and the cinematographic image to transport the reader and the viewer in a virtual, accessible, manageable, immersive and interactive territory, in a possible world situated between the utopian and the dystopian, the true and the false, the real and the illusory, finally, in a «virtual reality».

Esta tesis examina la representación de China que ofrecen la prensa y la narrativa española en el siglo XIX. El periodo del que se ocupa comprende entre los años 30 del siglo XIX hasta alrededor de 1900, teniendo en cuenta el relevo del japonismo por la chinoiserie. La tesis tiene como fuentes primarias textos españoles derivados de tres ámbitos. En primer lugar, la prensa ilustrada, que se considera el campo más fecundo de la reproducción de estereotipos del extranjero y más sensible a las tendencias artísticas; en segundo lugar, los principales libros de viaje a China escritos por diplomáticos españoles y, por último, las obras de ficción sobre China o sobre los chinos, tanto los publicados en la prensa como los publicados en volúmenes. La tesis plantea un paradigma analítico basándose en tres corrientes teóricas posmodernas: la representación, la imagología y el estereotipo, acudiendo a teóricos como S. Hall, D. H. Pageaux y R. Amossy. En el planteamiento, estas tres ramas disciplinarias confluyen en un enfoque poscolonial, atendiendo a las críticas y metodologías de E. W. Said y H. Bhabha. En cuanto a la percepción de la otredad desde un punto de vista historiográfico, se recurre a la historia del conocimiento sobre China desde España, a fin de determinar de antemano una imagen preconcebida de aquel país oriental en España hasta entrado el siglo XIX. Asimismo, se presenta una historia cultural en la que se dará cuenta de los acontecimientos relevantes que condicionan el siglo XIX entre China y Europa, sobre todo, entre China y España. El análisis de corpus se perfila en tres capítulos entre los que se distribuyen los materiales de los tres tipos de fuentes. En primer lugar, se examina la representación textual del país oriental en todo género de escritos, complementada por numerosos grabados dentro del periodo comprendido entre los años 30 hasta el fin de siglo y publicados en cuatro revistas: el Semanario Pintoresco Español (1836-1857), El Museo Universal (1857-1869), El Mundo Pintoresco (1858-1860) y La Ilustración Española y Americana (1869-1900 [1921]). A continuación, se ofrece un análisis de escritos de varios diplomáticos en China. Estos viajeros que cuentan su experiencia como testimonios directos y que representan China o proyectan una imagen literaria de aquel país oriental son Adolfo Mentaberry, Eduardo Toda, Enrique Gaspar y Luis Valera. Junto a ellos, se deben mencionar Sinibaldo de Mas, Pedro de Prat y Fernando de Antón del Olmet, los cuales publican sus escritos en la prensa. Finalmente, se abordan varias narraciones inspiradas en la China del siglo XIX, creadas por escritores españoles que no cuentan con una experiencia propia de viajar a China pero que conocen el país a través de testimonios indirectos, como la lectura. Estas obras pertenecen a los autores Enrique Bendito, Emilia Pardo Bazán, Magdalena de Santiago-Fuentes y Julián Bastinos. Finalizados los análisis, se propone una interpretación del funcionamiento interactivo de los conceptos representación, estereotipos, imagen e imaginario colectivo. Con tal propuesta teórica, se logra definir una evolución de los modos de representación y de las imágenes de China durante el siglo XIX. La tesis pretende contribuir al estudio de la representación de la otredad y la imagología, así como al estudio historiográfico de la interculturalidad entre Occidente y Oriente, especialmente, entre España y China. Además, con un espíritu de rescate, devuelve textos inéditos o faltos de un estudio sistemático a la crítica de hoy. Asimismo, tiene como finalidad última la de ofrecer claves para la comprensión mutua de ambas culturas, ya que analiza unos productos históricos y culturales que se vinculan estrechamente con algunas opiniones de consenso social todavía vigentes en España sobre China. / This thesis examines the representation of China offered by the Spanish press and literary narrations in the 19th century. It deals with the period included between the 1830s and 1900 when Japonism replaced Chinoiserie as the main oriental influence. The thesis has as its primary sources Spanish texts in three areas. First, the illustrated press, which is considered the most prolific and capable of reproducing stereotypes of the foreign countries, and also the most sensitive to the artistic trends; second, the main travel writings about China by Spanish diplomats; and finally, works of fiction about China or the Chinese, either published in the press or in volumes. The thesis presents an analytical paradigm based on three postmodern theoretical terms: representation, image and stereotype, as studied by theoreticians like S. Hall, D. H. Pageaux, R. Amossy. These three disciplinary branches converge in this thesis in a postcolonial approach, based on the reviews and methodologies of E. W. Said and H. Bhabha. Regarding the perception of otherness from a historiographical point of view, this thesis explains the history of knowledge about China from Spain in order to predetermine a preconceived image of that oriental country in Spain until the 19th century. Moreover, a cultural history will be presented based on the main events highlighting the China-Spain relationship of the nineteenth century. The analysis of the corpus is divided into three chapters including the materials of the three types of sources. First, the representation of China is examined in all kinds of written texts, complemented by numerous engravings within the period from the 30s to the end of the century in four journals, which are: Semanario Pintoresco Español (1836-1857), El Museo Universal (1857-1869), El Mundo Pintoresco (1858-1860) and La Ilustración Española y Americana (1869-1900 [1921]). Then, an analysis of texts written by several diplomats in China is offered. These travelers, who either tell their Chinese experience as a direct testimony and represent China, or project a literary image of that oriental country, are: Adolfo Mentaberry, Eduardo Toda, Enrique Gaspar y Luis Valera. With them, we should mention Sinibaldo de Mas, Pedro de Prat and Fernando de Antón del Olmet, who published their writings in the press. Finally, several narratives inspired by nineteenth-century China are discussed. They are created by Spanish writers who do not have their own experience of travelling to China but who know the country through indirect testimonies, like reading. These works belong to the authors: Enrique Bendito, Emilia Pardo Bazán, Magdalena de Santiago-Fuentes and Julián Bastinos. After completion of the analysis, an interpretation of the interactive functioning of the following concepts is proposed: representation, stereotypes, image and collective imagination. With this theoretical proposal, it is possible to define an evolution of the ways of representation and the images of China during the 19th century. The thesis aims to contribute to the study of the representation of otherness and imagology, besides the historiographical study of multiculturalism between the West and the East, especially between Spain and China. Furthermore, for the sake of bringing to light certain works, it recovers unpublished texts or texts missing a systematic study. It also has the ultimate aim to offer keys to the understanding of both cultures discussed, since it analyzes some historical and cultural products that are closely related to some widely held opinions about China still existing in Spain.

This paper is the result of the research done for the study of Josep Pla’s Viatge a l’Amèrica del Sud (1957), from the volume En Mar (OC 18) 1971, made up from his collaborations for the magazine Destino. In this book, the author presents, with the structure of a diary, the experiences of the trip he made for the magazine between December 1957 and March 1958, and which were published as "Cartas" and articles in the section "Calendario sin fechas”" between January and July 1958. This study has its origins in the interest to show some of the literary projects resulting from the trips Pla made between 1956 and 1960 for the magazine Destino, projects which were already introduced in L’aventura breu i meravellosa com un foc d’encenalls (Josep Pla’s collaborations for Destino, 1956-1960), in 2008, a piece of work for the Master in Catalan Studies: language and Literature and its applications, written by Rosa M. Perez Buendia, the author of this thesis. An important part of the investigation focuses on the analysis of the material for the press which Pla chose, organized, revised and rewrote to develop a story based on a real journey. In the first place, we present the articles published in Destino: an analysis according to the contents and the literary vision of these writings. Also, by comparing them with the original manuscripts, we take into consideration the role of the correctors in the final product. Next, there is an approach to how the book was actually made, referring to the texts Pla had already published and those which had been created for the occasion. As for the texts from Destino, we study which of them the author chose and the order in which they appear in the diary, because, unlike the reports, they followed the route of the voyage made in 1958. We also examine the way they were presented in the book: either reworded or as a report. Regarding the newly created material, we suggest the existence of a travel journal. Finally, through the original manuscripts, we have collected data on the role of editors in the final product. Last but not least, there is the literary study of the book Viatge a l’Amèrica del Sud (1957) which focuses on the newly created diary, taking also into consideration part of what has been analyzed with respect to the texts from Destino and its shaping into a diary. In this paper, apart from the actual study of a book based on Pla’s collaborations for Destino, we raise several questions about the relationship between the writer and the press, specifically the magazine Destino: the conditions under he worked, how he worked and what the relationship with the owner of the magazine, Josep Verges, was like. We also mention other aspects, such as the projects during this period, especially those which refer to the publisher Selecta and the relationship with the publisher Joseph M. Cruzet. We also take into account the political context, both at the time of the trip and at the time when the book was published, in 1971.