Decadas da Asia, que tratam dos mares, que descobriram, armadas, que desbaratarão, exercitos, que vencerão, e das acçoens heroicas, e façanhas bellicas, que obrarão os portuguezes nas conquistas do oriente : escritas por Diogo do Couto, cronista e guarda mor da Torre do Tombo do Estado da India

Diogo do Couto nasceu em Lisboa em 1542 e morreu em Goa em 1616. Historiador e guarda-mor do Tombo de Goa. Continuou por ordem de Filipe II as Décadas de João de Barros, escrevendo da quarta à décima segunda. Segundo Inocêncio, as ‘Décadas’ IV, V, Vl, VII e VIII foram todas reimpressas, saindo juntamente com a IX, ou o seu epilogo, que, pela primeira vez então se estampou com o titulo ‘Decadas da Asia, que tratam dos mares’. A edição de 1736 não contém os cinco livros da ‘Década XII’, apesar de já terem sido publicados naquela época

Regimento que V. A. manda dar à Junta do Comercio Geral para usar daqui em diante delle, na maneira que nelle se declara : para V. A. ver / Martim de Brito Couto o fez

A Junta não durou muito. Foi extinta em 1720.

A metáfora e a intertextualidade: uma realização multicultural na língua portuguesa

Este estudo teve a finalidade de descrever, num corpus literário de iniciação, tanto a metáfora conceptual e suas manifestações lingüísticas quanto à intertextualidade, como caminhos possíveis para um processo de compreensão construtivo e autônomo, em textos de língua portuguesa produzidos em culturas diferentes. Selecionamos, como material de investigação dos aspectos estudados, na literatura brasileira, uma trilogia metaliterária de Lygia Bojunga Nunes, na literatura portuguesa, dois contos de Sophia de Mello Breyner Andresen, e na literatura africana, optamos pela representação moçambicana com uma novela de Mia Couto. As obras das duas primeiras autoras são lidas por jovens entre 14 a 17 anos nos seus países de origem e a obra de Mia Couto está aqui relacionada por ser uma possibilidade e um enriquecimento para o leitor em formação. Trabalhamos com a metáfora inserida nos fundamentos da Semântica cognitiva, porque traz como preceito básico o desvelamento das associações que vão embasar nossos esquemas mentais e cujo conhecimento vai-nos habilitando a uma autonomia para relacionar sentidos e perceber que até a mais obscura emissão vai ganhar ares de previsibilidade por conta das nossas experiências, dos textos que buscamos na memória e do contexto que construímos com os dados lingüísticos que preenchem a moldura de um dado cenário. A metáfora, porém, se mostrou produtiva em nossas análises porque associamos a sua gênese conceptual com a sua função pragmática. É nessa fusão que ela se faz língua, se faz pujante, desviante e revela para o interlocutor as marcas que a remetem para a circularidade original, ou seja, o conceito da qual ela foi gerida. Verificamos, na aplicação da teoria no corpus analisado, que, através dos fundamentos da metáfora conceptual e da intertextualidade, podemos compreender o que é universal e o que é cultural nas nossas expressões literárias e que a fronteira entre essas duas dimensões não fratura o diálogo que se faz urgente e necessário, para a defesa de uma cultura lusófona

Integrated Chest Image Analysis System "BU-MIA"

We introduce "BU-MIA," a Medical Image Analysis system that integrates various advanced chest image analysis methods for detection, estimation, segmentation, and registration. BU-MIA evaluates repeated computed tomography (CT) scans of the same patient to facilitate identification and evaluation of pulmonary nodules for interval growth. It provides a user-friendly graphical user interface with a number of interaction tools for development, evaluation, and validation of chest image analysis methods. The structures that BU-MIA processes include the thorax, lungs, and trachea, pulmonary structures, such as lobes, fissures, nodules, and vessels, and bones, such as sternum, vertebrae, and ribs.

Localization of monoterpenoid indole alkaloid (MIA) biosynthesis by in situ hybridization (ISH)

Monoterpenoid indole alkaloids (MIA) are among the largest and most complex group of nitrogen containing secondary metabolites that are characteristic of the Apocynaceae plant family including the most notable Catharanthus roseus. These compounds have demonstrated activity as successful drugs for treating various cancers, neurological disorders and cardiovascular conditions. Due to the low yields of these compounds and high pharmacological value, their biosynthesis is a major topic of study. Previous work highlighting the leaf epidermis and leaf surface as a highly active area in MIA biosynthesis and MIA accumulation has made the epidermis a major focus of this thesis. This thesis provides an in-depth analysis of the valuable technique of RNA in situ hybridization (ISH) and demonstrates the application of the technique to analyze the location of the biosynthetic steps involved in the production of MIAs. The work presented in this thesis demonstrates that most of the MIAs of Eurasian Vinca minor, African Tabernaemontana e/egans and five Amsonia species, including North American Amsonia hubrichitii and Mediterranean A. orienta/is, accumulate in leaf wax exudates, while the rest of the leaf is almost devoid of alkaloids. Biochemical studies on Vinca minor displayed high tryptophan decarboxylase (TOe) enzyme activity and protein expression in the leaf epidermis compared to whole leaves. ISH studies aimed at localizing TOe and strictosidine synthase suggest the upper and lower epidermis of V. minor and T. e/egans as probable significant production sites for MIAs that will accumulate on the leaf surface, however the results don't eliminate the possibility of the involvement of other cell types. The monoterpenoid precursor to all MIAs, secologanin, is produced through the MEP pathway occurring in two cell types, the IPAP cells (Gl0H) and epidermal cells (LAMT and SLS). The work presented in this thesis, localizes a novel enzymatic step, UDPG-7-deoxyloganetic acid glucosyltransferase (UGT8) to the IPAP cells of Catharanthus longifolius. These results enable the suggestion that all steps from Gl0H up to and including UGT8 occur in the IPAP cells of the leaf, making the IPAP cells the main site for the majority of secologanin biosynthesis. It also makes the IPAP cells a likely cell type to begin searching for the gene of the uncharacterized steps between Gl0H and UGT8. It also narrows the compound to be transported from the IPAP cells to either 7-deoxyloganic acid or loganic acid, which aids in the identification of the transportation mechanism.

Functional Characterization of Monoterpenoid Indole Alkaloid (MIA) Biosynthetic Genes in Catharanthus roseus

The monoterpenoid indole alkaloids (MIAs) of Madagascar periwinkle (Catharanthus roseus) are known to be among the most important source of natural drugs used in various cancer chemotherapies. MIAs are derived by combining the iridoid secologanin with tryptamine to form the central precursor strictosidine that is then converted to most known MIAs, such as catharanthine and vindoline that dimerize to form anticancer vinblastine and vincristine. While their assembly is still poorly understood, the complex multistep pathways involved occur in several specialized cell types within leaves that are regulated by developmental and environmental cues. The organization of MIA pathways is also coupled to secretory mechanisms that allow the accumulation of catharanthine in the waxy leaf surface, separated from vindoline found within leaf cells. While the spatial separation of catharanthine and vindoline provides an explanation for the low levels of dimeric MIAs found in the plants, the secretion of catharanthine to the leaf surface is shown to be part of plant defense mechanisms against fungal infection and insect herbivores. The transcriptomic databases of Catharanthus roseus and various MIA producing plants are facilitating bioinformatic approaches to identify novel MIA biosynthetic genes. Virus-induced gene silencing (VIGS) is being used to screen these candidate genes for their involvement in iridoid biosynthesis pathway, especially in the identification of 7-deoxyloganic acid 7-hydroxylase (CrDL7H) shown by the accumulation of its substrate, 7-deoxyloganic acid and decreased level of secologanin along with catharanthine and vindoline. VIGS can also confirm the biochemical function of genes being identified, such as in the glucosylation of 7-deoxyloganetic acid by CrUGT8 shown by decreased level of secologanin and MIAs within silenced plants. Silencing of other iridoid biosynthetic genes, loganic acid O-methyltransferase (LAMT) and secologanin synthase (SLS) also confirm the metabolic route for iridoid biosynthesis in planta through 7-deoxyloganic acid, loganic acid, and loganin intermediates. This route is validated by high substrate specificity of CrUGT8 for 7-deoxyloganetic acid and CrDL7H for 7-deoxyloganic acid. Further localization studies of CrUGT8 and CrDL7H also show that these genes are preferentially expressed within Catharanthus leaves rather than in epidermal cells where the last two steps of secologanin biosynthesis occur.

Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)

The various steps of monoterpene indole alkaloid (MIA) biosynthesis are known to occur in specialized cell types and subcellular compartments. Numerous MIAs display powerful biological activities that have led to their use as pharmaceutical treatments for cancer, hypertension and malaria. Many of these compounds accumulate on the leaf surface of medicinally important Apocynaceae plants, which led to the recent discovery and characterization of an ABC transporter (CrTPT2) that was shown to mobilize catharanthine from its site of biosynthesis in epidermal cells to the leaf surface of Catharanthus roseus. Bioinformatic analysis of transcriptomes from several geographically distant MIA-producing species led to the identification of proteins with high amino acid sequence identity to CrTPT2. Molecular cloning of a similar transporter (VmTPT2) from Vinca minor was carried out and expressed in a yeast heterologous system for transport experiments and functional characterization. In planta studies involved transcript expression analysis of the early MIA biosynthetic gene VmTDC and putative transporter VmTPT2, and alkaloid profile analyses. RT-qPCR results showed that VmTPT2 expression increased 15-fold between the first two leaf pairs, and high levels were maintained across older leaves. The alkaloid accumulation profile on leaf surfaces matched that of VmTPT2 expression, especially for the MIAs vincadifformine and vincamine. Gene expression and alkaloid profile analyses suggest that the functional protein may act as a similar transporter to CrTPT2. However, although VmTPT2 had 88.4% identity at the amino acid level to CrTPT2, it displayed an altered expression pattern in planta across developing leaves, and functional characterization using a previously developed yeast heterologous system was unsuccessful due to difficulties with reproducibility of transport assays.

Obras del doctor d. José Bernardo Couto

UANL

Breu informe sobre les propostes genu??nes de l'Acad??mia Valenciana de la Llengua. 'Breve informe sobre las propuestas genuinas de la Acad??mia Valenciana de la Llengua'

Los autores comentan la situaci??n de conflicto ling????stico de secesi??n del valenciano y el catal??n despu??s de la creaci??n de la Acad??mia Valenciana de la Llengua.

L???educaci?? sentimental d???una joventut perduda : fragments de vida boh??mia del Par??s finisecular i la Gran Guerra

Resumen basado en el de la publicaci??n

0 retrato e a moldura : memória e oralidade em cada homem é uma raça

En este trabajo se ha realizado un análisis de cuatro cuentos de Mia Couto (2005) pertenecientes al libro Cada homem é uma raça: O embondeiro que sonhava pássaros ; A princesa russa ; O pescador cego y A lenda da noiva e do forasteiro . El estudio, bajo la perspectiva de memoria y oralidad, mantiene en foco la observación sobre la transformación de los componentes de la realidad sociocultural e histórica de Mozambique en elementos de ficción literaria. Ese recorrido esclarece, en parte, la unidad orgánica que constituye la obra y que gira en torno de los elementos de la tradición, la memoria y la oralidad. Este punto es un importante marcador de diferencias, pues las sociedades escritas han dado menos importancia a lo que es transmitido oralmente, dejando lo que es tradición en un segundo plano. Se trata de una comprensión que acabó por provocar la distorsión del pensamiento sobre lo que es tradición oral, algo que no se resume a leyendas, cuentos de hadas, folclores y danzas. De esta manera ha de considerarse a la memoria inscripta en cada símbolo como algo que justifica al ser y que lo identifica como individuo poseedor de una historia colectiva

Inovação do método MIA-QSAR: aplicação para doenças tropicais negligenciadas

Multivariate image analysis applied to the quantitative structure-activity relationships (MIA-QSAR) is a 2D QSAR technique that has been presenting promising outcomes for the development of new drug candidates, due to its simplicity, rapidity and low cost. In this way, the present study aims at introducing, consolidating and improving the new dimensions named aug-MIA-QSAR and aug-MIA-QSARcolor, as well as applying them to the study of neglected diseases, in order to obtain new drug targets using chemico-biological interpretation of the MIA molecular descriptors. Four compound data sets with experimental bioactivities against Chagas disease, malaria, dengue and schistosomiasis were evaluated using three approaches: MIA-QSARt, aug-MIA-QSAR and aug-MIA-QSARcolor. In general, representations of atoms as spheres with different colors and sizes proportional to the corresponding van der Waals radii (aug-MIA approaches) improved the predictive ability and interpretability in all data sets. The use of colors proportional to the Pauling´s electronegativity showed that MIA descriptors are capable of identifying periodic properties relevant for the studied activity. Finally, solid colors instead of spotlighted atoms allowed a correct identification of atoms by means of pixel values in the studies for malaria, dengue and schistosomiasis, which were, subsequently, useful for the chemical interpretation related to the bioactivity. It can be inferred that semicarbazones and thiosemicarbazones derivative with a tri-substituted ring in R1 group and a trifluoro methyl group in the R 3 position instead of a chlorine antitripanossoma resulted in higher activity. The antimalarial activity of quinolon-4(1H)imines can be improved if: 1) R1 and R2 are electron donor groups, 2) R3 has long aminoalkyl chains, and 3) R4 possesses substituents with big atomic volume. In the study for dengue, it was found that tetrapeptides with unbranched small size amino acids in the A1 and A4 positions can increase the substrate affinity (Km) to the NS3 protein, and when in A1 and A2 positions, the substrate cleavage rate (kcat). On the other hand, acidic amino acids in the A2 and A4 positions were found to be related with low substrate affinity to the NS3 protein and when present in A1, with low substrate cleavage rate. Finally, the presence of metoxy substituents in R1 (or R2) and R5 in the neolignan backbone can favor their antischistosomal activity.