A prospecção e síntese de novos derivados de 8-hidroxiquinolina está em ascensão devido às suas diversas atividades biológicas. Neste trabalho é relatada a síntese e avaliação da atividade antimicrobiana de novos derivados contendo uma sulfonamida substituída na posição 5 da 8-hidroxiquinolina ou um grupamento aminossubstituído na posição 7 da 5-cloro-8-hidroxiquinolina ou 5-cloro-8-metoxiquinolina. Os derivados 5-sulfonamidas foram preparados por clorossulfonação seguida da reação com a amina apropriada. Os derivados 7-aminossubstituído foram sintetizados através da metilação da hidroxila da posição 8, seguida da reação de cross-coupling catalisada por paládio e desmetilação. A avaliação da atividade antimicrobiana foi realizada através do método de microdiluição em caldo. Dentre os compostos sintetizados, 5a (da série 5-sulfonamidas) foi o mais potente, sendo ativo contra todas as espécies fúngicas testadas, além de apresentar importante atividade contra cepas de Staphylococcus aureus, e baixa toxicidade contra células VERO. Isso sugere que a introdução de um grupamento retirador de elétrons em para no substituinte arila da posição 5 é importante para a atividade antimicrobiana. Ainda, a nanoemulsão preparada contendo 5a manteve a atividade antifúngica da substância contra espécies de Candida spp. A série 7-aminossubstituído também apresentou resultados muito interessantes. Desta série, o composto 5i foi o mais potente. Isso sugere que grupamentos heterocíclicos hidrofílicos na posição 7 podem favorecer a atividade antifúngica. A presença da hidroxila livre na posição 8 parece ser essencial para a atividade antifúngica, pois os derivados protegidos por uma metila foram pouco ativos. Os derivados de 8-hidroxiquinolina 5a e 5i podem ser considerados para estudos posteriores na busca de novos agentes antimicrobianos. / The synthesis and screening of new 8-hydroxyquinoline derivatives is growing, due to their various biological activities. In this work, the synthesis and antimicrobial evaluation of new derivatives containing a substituted 5-sulfonamide in the 8-hydroxyquinoline or a substituted amino group at the 7-position of the 5-chloro-8-hydroxyquinoline or 5-chloro-8-methoxyquinoline is reported. The 5-sulfonamide derivatives were prepared by chlorosulfonation followed by the reaction with the appropriate amine. The 7-amino derivatives were synthesized by methylation of the 8-hydroxyquinoline, followed by palladium-catalyzed cross-coupling reaction and demethylation. The antimicrobial evaluation was tested by the broth microdilution method. Among all the prepared compounds, 5a (from the 5-sulfonamide series) was the most potent, being active against all the fungal species tested, while also showing important activity against Staphylococcus aureus strains, and low toxicity against VERO cells. This suggests that the introduction of an electron-withdrawing group at para-position of the N-aryl substituent is important for the activity. In addition, the prepared 5a nanoemulsion maintained the antifungal activity of the compound against Candida spp. The 7-amino series has also presented interesting results. In this series, 5i was the most potent compound. This suggests that the hydrophilic heterocyclic substituent at the 7-position was favorable to antifungal activity. The presence of the free hydroxyl at the 8-position is important for the antifungal activity, since the methyl-protected derivatives were poorly active. The 8-hydroxyquinoline derivatives 5a and 5i may be considered for further studies in the search for novel antimicrobial agents.

The object of this thesis is the analysis of the external debt of countries which are members of the G-8. The external debt is researched through individual sectors of economy. Also there are described debt instruments and all the factors which can influence the external debt. The last part of this thesis analyses situation and development of individual debt instruments and the impact on total external debt.

According to the UNAIDS global report 2013, an estimated 6.1 million people are living with human immunodeficiency virus (HIV) in South Africa. The incidence of Kaposi sarcoma (KS) has increased dramatically since the Acquired Immunodeficiency Syndrome (AIDS) epidemic. Of the estimated 66 200 cases of KS worldwide, 58 800 are thought to have occurred in SSA (Parkin 2002). However, there remains a paucity of published data about KS from South Africa. This retrospective study was conducted to describe the epidemiology of KS at Chris Hani Baragwanath Academic Hospital (CHBAH) and to determine possible links among the CD4 counts, intensity and distribution of human herpes virus 8 latency- associated nuclear antigen 1 (HHV8 LNA-1) immunohistochemical staining and the stage of KS. Nine hundred and thirty eight histopathology reports of KS diagnosed in 901 patients at CHBAH between 2005 and 2009 were reviewed and demographic data (age, gender, topographic site, CD4 count, HIV status, KS stage, HHV8 LNA-1 staining, concomitant pathology) were recorded. The H&E stained sections and HHV8 LNA-1 immunostains of a cohort of 127 cases were subsequently reviewed and categorised with regard to intensity and distribution of staining. The male:female ratio was 1,2:1. The mean age was 36,8 years (standard deviation {SD} 10,2 years) and the median CD4 count 127,5 cells/mm3 (quartile range {QR} 184,5 cells/mm3). Lower limb skin biopsies accounted for 49,6% of cases. Concomitant pathology was seen in 4,6% of cases. Infections and inflammatory dermatoses were the most frequently diagnosed concomitant pathology in cutaneous biopsies. Paediatric, visceral and endemic KS accounted for only limited proportions of cases (1,44% of patients; 1,4% and 1,3% respectively). There was a significant difference in the distribution of HHV8 LNA-1 staining in patch versus nodular KS (p = 0,011). The CD4 counts were not predictive of KS Page | v stage (p = 0,701) or the intensity (p = 0,877) and distribution (p = 0,846) of HHV8 LNA-1 immunohistochemical staining. This study highlights the epidemiology of KS and the variability in HHV8 LNA-1 immunohistochemical staining across CD4 counts and stages of KS.

No description available.

Tese de mestrado integrado. Engenharia Civil (Especialização em Estruturas). Faculdade de Engenharia. Universidade do Porto. 2010

A presente dissertação pretende inventariar, sistematizar e estudar o conjunto de adornos metálicos alti-mediévicos conhecidos no território português. A nossa atenção incidiu sobre os elementos metálicos relacionados com o vestuário e o adorno do corpo, cronologicamente balizados entre os séculos V e VIII da nossa Era. Apesar de uma parte significativa dos materiais já se encontrar publicada, em estudos dispersos, faltava um inventário sistemático e uma visão de conjunto. A maior parte dos referidos materiais encontra-se depositada em Museus ou noutras instituições públicas, procedendo fundamentalmente de necrópoles de inumação, mas também, em alguns casos, de povoados ou villasreocupadas. Muitos referem-se a achados isolados ou absolutamente descontextualizados. Através do inventário/catálogo realizado, onde se incluíram todas as ocorrências de que temos conhecimento, pretendemos proporcionar uma sistematização de tipologias, cronologias e características produtivas. Ao longo da Dissertação procuramos analisar a evolução de elementos de adorno, a sua variabilidade, a relação com práticas de vestuário e de inumação, não esquecendo o seu enquadramento nos acontecimentos políticos, sociais e religiosos da sua época.

Depuis les années 2000, le développement de la spectroscopie Raman à exaltation de pointe (TERS) a permis l’accès de manière extrêmement localisée aux propriétés structurales et moléculaires à la surface de la matière et à des analyses physico-chimiques combinées. La technologie TERS associe les techniques de microscopie à sonde locale - ici le microscope à force atomique (AFM) - avec le champ proche optique. Elle bénéficie en particulier de la génération, à la surface métaux nobles, de plasmons de surface à l’origine d’exaltation d’ondes électromagnétiques pouvant être confinées dans un volume sub-longueur d'onde à l'extrémité des sondes AFM-TERS. Aujourd'hui le principal verrou technologique en TERS est la conception des sondes AFM en termes de reproductibilité à échelle nanométrique, et de fabrication en série. Ce travail de thèse effectué dans le cadre d’une thèse CIFRE (HORIBA Scientific) a eu pour but de concevoir un nouveau type de sonde AFM-TERS répondant aux exigences de performances et de fabrication actuelles. Pour atteindre cet objectif, une étude de simulation numérique a conduit à proposer une nanostructuration métallique de l’extrémité d’un levier AFM, afin de conduire à une exaltation électromagnétique optimisée. Un procédé de nano- et micro-fabrication a été développé au sein de la plateforme de micro et nano-fabrication de l'IEMN, combinant lithographie électronique et optique, évaporation métallique et gravure sur wafers silicium. Il permet la réalisation en série de sondes AFM dont chaque extrémité est composée d'une nano-antenne métallique de taille sub-longueur d'onde, composée d'un nanodisque supportant un nanocône. La méthode de fabrication proposée permet un contrôle des réponses plasmoniques en termes d’amplification du champ et d’accordabilité de la résonance, qui sont la clé des performances en spectroscopie Raman à exaltation de pointe. Une étude sur l’évaporation inclinée lors du procédé de nano-fabrication développé par lithographie électronique a également été réalisé dans le but de contrôler la forme des nanoparticules – de forme conique à cylindrique avec des parois poreuses -- isolées ou en réseaux denses. Les simulations numériques suggèrent que de tels objets peuvent être des candidats potentiels pour le TERS ou le SERS (spectroscopie Raman à exaltation de surface). / Since the start of the 2000s the evolution of tip-enhanced Raman spectroscopy (TERS) has enabled the simultaneous measurement of localized structural, molecular, and physicochemical properties. TERS technology combines scanning probe microscopy -- atomic force microscopy (AFM) -- with near field optical microscopy. The combined technique is referred to as AFM-TERS. The technique harnesses and exploits the generation of surface plasmons on metal surfaces. These plasmons lead to the generation of confined electromagnetic waves in a sub-wavelength volume at the very tip of the AFM-TERS probe. The main technological challenge today is the design and optimization of an AFM-TERS probe having nanometer-sized dimensions -- and the controlled, reproducible batch fabrication of such structures. The objective of the work presented in this PhD thesis was to design, fabricate, and characterize a new type of AFM probe capable of bettering the current state-of-the-art performances. The PhD was carried out in collaboration with HORIBA and funded partly by a French ‘CIFRE’ grant. In order to meet these objects, comprehensive numerical modelling led to the design of an optimized metal nanostructuring having maximum electromagnetic exaltation -- placed at the extremity of a silicon-based AFM cantilever. A new combined micro and nano fabrication process was developed to achieve this -- to be performed using the existing equipment found in the IEMN cleanroom. The process encompasses techniques such as masking using electron beam (ebeam) lithography and UV photolithography, thermal evaporation of metals and ‘lift-off’ techniques, and highly-controlled dry etching of small silicon mesas structures and deep etching for MEMS cantilever releasing. The process enables the batch-fabrication manufacture of AFM-TERS probes containing matter on the millimeter scale (the silicon probe support), the micrometer scale (the silicon cantilever), and the nanometer scale (the combined metallic disk and cone having sub-wavelength dimensions). This method allows nanostructuring on the optical/plasmonic behavior of TERS probes, the key factor which will lead to higher performance in TERS. Finally, a further study concerning the inclined evaporation of metallic nanostructures via an ebeam-derived lithographic shadow mask was performed in order to control the size and shape of the nanostructuring. The study proved this approach to be feasible. Furthermore, numerical modelling of such structures suggests that they are potential original candidates for both TERS and SERS (surface-enhanced Raman spectroscopy).

Prior research suggests that the use of accounting information differs substantially by investor class. My analysis extends this line of research to the area of SEC Form 8-K filings. Prior research also provides mixed evidence on the informativeness of these filings. I hypothesize that the method of the disclosure is an important factor in evaluating 8-K usefulness to varying types of investors. Specifically, the timing, venue, and packaging of these accounting disclosures affect their use by investors. Regulation Fair Disclosure (2000) considers both press releases and 8-K filings as broad-based disclosures that do not favor any investor class. I, however, identify five unique informational settings in which 8-K filings occur. The five settings are: a concurrent 8-K event and filing (with or without a press release), a filing which precedes the press release, a press release that precedes the filing, an 8-K event that precedes a filing and/or press release, and the 8-K event alone. I examine the similarities and differences in trading by small and large investors across these settings. The identification of these empirical regularities with respect to disclosure form should be particularly useful to policy makers seeking to implement level playing field objectives with respect to public disclosures. My findings show that the relative trading activity to 8-K filings is different by the type of disclosure. Differential trading activity was found to be more pronounced in disclosure settings that contained a public announcement. In addition, the type of Form 8-K disclosure also had an effect on the differential trading activity. Form 8-K filings of acquisition or disposition of assets were associated with the most pronounced responses. My findings show the differential trading activity to these filings differs from other accounting events such as earnings announcements and annual report filings.

Type IV secretion systems have been identified in several human pathogens including Bordetella pertussis, Helicobacter pylori, and Legionella pneumophila. These systems are responsible for the translocation of virulence proteins and/or DNA, thereby playing an important role in the pathogenesis of infection and plasticity of genomes. Burkholderia cenocepacia is an important opportunistic human pathogen, particularly in persons with cystic fibrosis (CF). Respiratory tract infection by B. cenocepacia in CF patients is often associated with a decline in respiratory function, and can result in acute systemic infection. Burkholderia cenocepacia strain K56-2 is part of the epidemic and clinically problematic ET12 lineage. Two type IV secretion systems have been identified in this strain; one system is plasmid encoded (designated the Ptw type IV secretion system) whereas the other is chromosomally encoded (designated the VirB/D type IV secretion system) and shows homology to the Agrobacterium tumefaciens VirB/D4 type IV secretion system. It was determined that the plasmid encoded Ptw system is a chimeric type IV secretion system composed of VirB/D4-like elements and F-specific subunits. More recently, it was found that this system translocates a protein effector (PtwE1) that is cytotoxic to plant cells. It was also determined that the positively charged C-terminal region of PtwE1 is important for translocation via the Ptw type IV secretion system. Strains of the epidemic B. cenocepacia PHDC lineage contain only a chromosomal VirB/D4-like type IV secretion system (designated BcVirB/D); and a putative effector protein associated with this system has been identified that has C-terminal transport signal and sequences different from the effectors of the Ptw type IV secretion system. It has also been shown that a competing plasmid substrate and a plasmid fertility inhibition factor act to render B. cenocepacia of the PHDC lineage incapable of expressing a plant phenotype. Thus, three type IV secretion systems have been identified in epidemic B. cenocepacia lineages. From two of these, an effector has been identified that has cytotoxic effects on eukaryotic cells, and at least one of these type IV secretion systems is able to translocate DNA substrates.

La tesi és una monografia sobre Ramon Xuriguera i Parramona (Menàrguens, 1901 - Bergerac, 1966), un autor poc conegut i, segurament, infravalorat de la nostra història cultural. L'estudi es divideix en nou capítols que avancen cronològicament. El primer s'ocupa del punt de partida de Xuriguera en el món de la literatura i del periodisme. El segon indaga en els anys de formació a la ciutat de Lleida i es comenta, de manera preferent, el paper fonamental que va tenir en l'intent d'articular unes propostes culturals modernes des de la revista Lleida. El tercer té com eix les tasques desenvolupades a París i l'anàlisi del seu primer llibre, Els exiliats acusen. El quart descriu la tornada de Xuriguera a les Terres de Ponent amb l'encàrrec de dirigir el diari republicà i d'esquerres La Jornada. El cinquè se centra en l'exercici de l'activitat cultural i política a Barcelona: articles per a periòdics i revistes com La Publicitat, Mirador, La Humanitat, La Rambla i L'Horitzó; novel·les i reculls que s'emmarquen dins el corrent de la narrativa psicològica, Volves grises, Desordre i Espills dormits; assaigs de tema polític i literari, Casanovas i L'aportació de l'occident català a l'obra de la Renaixença; i traduccions, Els infants terribles, de Jean Cocteau i Masako, de Kikou Iamata. El sisè examina l'activitat que desenvolupa al llarg de la guerra civil al servei de Catalunya i de la República alhora que redacta articles per a diverses revistes i dóna a conèixer els assaigs La repressió contra els obrers a Catalunya i Goya, pintor del poble, i la novel·la Destins. El setè gira al voltant de l'estada de Xuriguera a les viles occitanes de Mouleydier i Bergerac, un període en què, tot i dedicar-se al periodisme (en publicacions de l'exili català de França i d'Amèrica), a la creació literària (amb les novel·les Els Astruc i Tres nits i els assaigs Novel·les i novel·listes catalans i L'escola de pintura catalana, que han romàs inèdits) i a la traducció (Madame Bovary, de Gustave Flaubert), col·labora amb Joan Casanovas per impulsar el moviment polític conegut com a Unió i amb Josep Queralt per tal de fer renéixer les Edicions Proa a Perpinyà. El vuitè se circumscriu als anys en què, des de París, es converteix en un dels més ferms activistes en defensa de la cultura catalana (les emissions radiofòniques "París, fogar de cultura catalana"; els Jocs Florals del Centenari; el Patronat de Cultura Catalana Popular; i la creació de la delegació francesa d'Òmnium Cultural), malgrat no deixar de banda el periodisme, l'assaig i la traducció (les versions de Jean-Paul Sartre i de Simone de Beauvoir representen la incorporació d'aquests dos autors a les lletres catalanes). El novè i darrer passa revista a la repercussió que va causar en el món català la mort de Xuriguera. L'estudi es completa amb una sèrie d'annexos que tenen la finalitat d'acabar de perfilar la imatge que, sobre la figura de Xuriguera, s'ha anat proporcionant al llarg del discurs: inclouen una relació de l'obra literària, tant la publicada com la inèdita; una selecció dels articles periodístics; l'edició de les novel·les Els Astruc i Tres nits; una extensa mostra de l'epistolari; i una tria dels comentaris crítics apareguts a la premsa coetània sobre la seva producció. / The thesis is a monograph about Ramon Xuriguera i Parramona (Menàrguens, 1901- Bergerac, 1966), an author who is little known and probably little appreciated in our cultural history. The research is divided into nine chapters which, advance in chronological order. The first one is concerned with Xuriguera's firsts steps in the world of literature and journalism. The second one investigates his years of education in the city of Lleida and his fundamental role in some modern cultural proposals from the magazine called Lleida. The third one enquires into his works in Paris and analyses his first book, Els exiliats acusen. The fourth one describes his coming back to the west with the assignment of editing the left-wing republican newspaper La Jornada. The fifth one pays attention to his cultural and political activities in Barcelona: articles for newspapers and magazines such as La Publicitat, Mirador, La Humanitat, and L'Horitzó; works and writings which are in the psychological narrative, Volves grises, Desordre and Espills dormits; political and literary essays, Casanovas i L'aportació de l'occident català a l'obra de la Renaixença, and translations, Els infants terribles, by Jean Cocteau i Masako, by Kikou Iamata. The sixth one inspects his activities in the Spanish Civil War at the service of Catalonia and the Republic as well as his articles for several magazines and essays like La repressió contra els obrers a Catalunya and Goya pintor del poble and the novel Destins. The seventh one talks about Xuriguera's stay in Mouleydier and Bergerac, villages of Provence, a period in which even he devoted himself to journalism (publishing from the Catalan exile in France and America), literary creation (with the novels Els Astruc and Tres nits and the essays Novel·les i novel·listes catalans and L'escola de pintura catalana, which are still unpublished), and to translation (Madame Bovary, by Gustave Flaubert), collaborates with Joan Casanovas to promote the political movement known as "Unió" and with Josep Queralt in order to make "Edicions Proa" reappear in Perpinyà. The eight one centres on the years when, from Paris, he becomes one of the firmest activists defending Catalan culture (the broadcasts "Paris, fogar de la cultura Catalana"; the "Jocs Florals del Centenari"; the "Patronat de Cultura Catalana Popular"; and the creation of the French office of "Omnium Cultural"); however, he never leaves journalism, essay and translation (the translations of Jean-Paul Sartre and Simone Beauvoir represent the incorporation of these two authors to the Catalan arts). The ninth and last one enquires into the repercussions that Xuriguera's death caused in the Catalan world.The investigation is completed with a series of annexes which have the purpose of completing the picture of Xuriguera's personality. They include a list of works, published as well as unpublished; a selection of newspaper articles; the edition of the novels Els Astruc and Tres nits, an extensive sample of his collection of letters; and a selection of the critical commentaries which were published in the contemporary press about his works.