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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Homology modeling and structural analysis of the antipsychotic drugs receptorome

López Muñoz, Laura 22 June 2010 (has links)
Classically it was assumed that the compounds with therapeutic effect exert their action interacting with a single receptor. Nowadays it is widely recognized that the pharmacological effect of most drugs is more complex and involves a set of receptors, some associated to their positive effects and some others to the side effects and toxicity. Antipsychotic drugs are an example of effective compounds characterized by a complex pharmacological profile binding to several receptors (mainly G protein-coupled-receptors, GPCR). In this work we will present a detailed study of known antipsychotic drugs and the receptors potentially involved in their binding profile, in order to understand the molecular mechanisms of the antipsychotic pharmacologic effects.The study started with obtaining homology models for all the receptors putatively involved in the antipsychotic drugs receptorome, suitable for building consistent drug-receptor complexes. These complexes were structurally analyzed and compared using multivariate statistical methods, which in turn allowed the identification of the relationship between the pharmacological properties of the antipsychotic drugs and the structural differences in the receptor targets. The results can be exploited for the design of safer and more effective antipsychotic drugs with an optimum binding profile. / Tradicionalmente se asumía que los fármacos terapéuticamente efectivos actuaban interaccionando con un único receptor. Actualmente está ampliamente reconocido que el efecto farmacológico de la mayoría de los fármacos es más complejo y abarca a un conjunto de receptores, algunos asociados a los efectos terapéuticos y otros a los secundarios y toxicidad. Los fármacos antipsicóticos son un ejemplo de compuestos eficaces que se caracterizan por unirse a varios receptores simultáneamente (principalmente a receptores unidos a proteína G, GPCR). El trabajo de la presente tesis se ha centrado en el estudio de los mecanismos moleculares que determinan el perfil de afinidad de unión por múltiples receptores de los fármacos antipsicóticos.En primer lugar se construyeron modelos de homología para todos los receptores potencialmente implicados en la actividad farmacológica de dichos fármacos, usando una metodología adecuada para construir complejos fármaco-receptor consistentes. La estructura de estos complejos fue analizada y se llevó a cabo una comparación mediante métodos estadísticos multivariantes, que permitió la identificación de asociaciones entre la actividad farmacológica de los fármacos antipsicóticos y diferencias estructurales de los receptores diana. Los resultados obtenidos tienen interés para ser explotados en el diseño de fármacos antipsicóticos con un perfil farmacológico óptimo, más seguros y eficaces.
52

The Taiwanese Communist Party and the Comintern (1928-1931)

白安娜, ANNA BELOGUROVA Unknown Date (has links)
as English abstract / Oppressed by the severe surveillance of the Japanese police in Taiwan, short-lived Taiwanese Communist Party (TCP) (1928-1931) marked a significant step in the Taiwan’s anti-Japanese movement and social thought. The TCP was the first political organization in Taiwan to put forward the slogan of Taiwan’s independence. Following the Comintern’s activation in the East in 1920s, the first contacts between the Taiwan’s leftists and the Comintern representatives took place in early 1920s. Starting from 1927, the Comintern pursued the policy of activation of the communist movement in the colonies and establishment of communist parties in these countries. Established on the Comintern directive in Shanghai with the help of the Chinese Communist Party (CCP) and being subordinated to the Japanese Communist Party (JCP), the TCP was developing quite independently under the leadership of Xie Xuehong and in the close alliance with the Taiwan Cultural Association and the Taiwan Peasants Union, until the end of 1930 when the TCP established a contact with the Far Eastern Bureau (FEB) of the Comintern through the TCP Shanghai representative, Weng Zesheng, who served as liaison with the Comintern. As the result, the Comintern activated its work toward Taiwan, started dispatching emissaries to Taiwan who in the framework of the Comintern’s rhetoric of that time promoted the Party’s reform to eliminate the “opportunistic errors”. The activation of the Party’s work followed, the Union for Reorganization was established. The Comintern did not have chance to adjust the activity of the reformed TCP as within few months after the beginning of actual interaction between the Comintern and the TCP, the TCP was destroyed by arrests. The thesis is devoted to the Comintern’s role in the TCP’s establishment, development, reform, establishment of the Union for Reorganization, the Party’s activation and destruction. The research is based on the TCP files deposited in the former archive of the Comintern. The documents include the correspondence of the representative of the TCP, Weng Zesheng, with the Comintern FEB. The correspondence between Weng Zesheng and the FEB sheds light on the inner-party processes in the TCP, clarifies the essence of the inner-party struggle and reform, and explores the role of personal relations in the inner-party struggle which resulted in the UFR establishment without direct involvement of the Comintern. The available now text of the consultations of Weng Zesheng with the CCP representative Qu Qiubai makes it possible to clarify the CCP’s involvement in the TCP’s development and reform and to conclude as to whose directive it was to commence the struggle against Xie Xuehong. The TCP’s history was short but very intensive. Abandoned by its superior, the JCP, and not having relations with the international communist leadership, the TCP suffered lack of the financial and ideological support, and was left for the mercy of unpredictable fate of the exhausting inner factional struggle, still was able to survive under the “white terror” until the Party’s reorganization in 1931. According to the research results, the TCP inner-party struggles during 1928-1931 were in fact the result of resistance to emigrant party groupings who were attempting to take control over the TCP’s Taiwan based Party organization. Neither the JCP and the CCP, nor the Comintern had a real opportunity to influence the activities of the Taiwan-based communists. Taiwan’s communists overseas used the Comintern’s rhetoric and their contacts with the Comintern and the CCP to promote their agenda in the inner-party struggle. The implementation of the plans of Weng Zesheng and the opponents of Xie Xuehong in Taiwan on the Party’s reform and activation led to the Party’s destruction by the Japanese administration.

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