Síntesi de base sòlida de pèptids biarílics contenint 5-arilhistidines

Els aminoàcids biarílics es troben en una àmplia varietat de pèptids naturals amb important activitat biològica. Concretament, les arilhistidines formen part de les aciculitines, pèptids amb activitat citotòxica i antifúngica, La reacció de Suzuki-Miyaura és el mètode més versàtil per obtenir biarils assimètrics, encara que, fins el moment, no s'havia aplicat per a l'arilació de l'imidazole de la histidina. L'objectiu general d'aquesta tesi fou demostrar que es podia arilar l'imidazole de la histidina en fase sòlida mitjançant una reacció de Suzuki-Miyaura. En primer lloc, es sintetitzaren 4(5)-metil-5(4)-fenilimidazole i 4(5)-metil-5(4)-(2-metoxifenil)imidazole a través de l'acoblament creuat entre un N-benzilbromoimidazole i el corresponent àcid arilborònic. Posteriorment, s'arilaren 5-bromohistidines utilitzant diversos àcids arilborònics mitjançant una reacció de Suzuki-Miyaura assistida per irradiació micrones, tant en dissolució com en fase sòlida. I finalment, mitjançant aquesta metodología, es sintetitzaren pèptids antimicrobians contenint 5-arilhistidines actius contra bacteris gram-negatius responsables d'importants malalties en plantes com el foc bacterià.

Microcalcification evaluation in computer assisted diagnosis for digital mammography

In order to develop applications for z;isual interpretation of medical images, the early detection and evaluation of microcalcifications in digital mammograms is verg important since their presence is often associated with a high incidence of breast cancers. Accurate classification into benign and malignant groups would help improve diagnostic sensitivity as well as reduce the number of unnecessa y biopsies. The challenge here is the selection of the useful features to distinguish benign from malignant micro calcifications. Our purpose in this work is to analyse a microcalcification evaluation method based on a set of shapebased features extracted from the digitised mammography. The segmentation of the microcalcifications is performed using a fixed-tolerance region growing method to extract boundaries of calcifications with manually selected seed pixels. Taking into account that shapes and sizes of clustered microcalcifications have been associated with a high risk of carcinoma based on digerent subjective measures, such as whether or not the calcifications are irregular, linear, vermiform, branched, rounded or ring like, our efforts were addressed to obtain a feature set related to the shape. The identification of the pammeters concerning the malignant character of the microcalcifications was performed on a set of 146 mammograms with their real diagnosis known in advance from biopsies. This allowed identifying the following shape-based parameters as the relevant ones: Number of clusters, Number of holes, Area, Feret elongation, Roughness, and Elongation. Further experiments on a set of 70 new mammogmms showed that the performance of the classification scheme is close to the mean performance of three expert radiologists, which allows to consider the proposed method for assisting the diagnosis and encourages to continue the investigation in the sense of adding new features not only related to the shape