Os microrganismos podem apresentar-se tanto em forma de vida livre como aderidos a uma superfície ou interface ar-líquido, formando comunidades complexas e dinâmicas conhecidas como biofilmes. Nos últimos anos, com o avanço das pesquisas em nível molecular, foi identificado que a maioria das bactérias utilizam guanosina monofosfato (3´-5´)-cíclica dimérica (c-di-GMP) como um segundo mensageiro. De forma geral, essa molécula controla a sinalização celular, virulência, comunicação entre células e a expressão de proteínas relacionadas com o fenótipo de biofilmes, em resposta à sua concentração intracelular. Sua síntese e degradação são controladas respectivamente por diguanilto ciclases (DGCs) contendo domínio GGDEF e fosfodiesterases (PDEs) que possuem os domínios EAL ou HD-GYP. Em Pseudomonas aeruginosa (PA14) foi identificada uma nova classe de receptor específico para c-di-GMP, a proteína transmembranar PelD, cuja porção citoplasmática contém os domínios GAF e GGDEF degenerado. Sua modulação através desse dinucleotídeo controla a produção de exopolissacarídeos pelos componentes do conservado operon pel e influencia diretamente na capacidade de formação de biofilmes. Devido à escassez de dados a respeito dos eventos moleculares do mecanismo de sinalização mediado por c-di-GMP, este trabalho teve como objetivo principal a caracterização biofísica/estrutural da proteína PelD, bem como o reconhecimento de interação entre este ligante e a porção citoplasmática da proteína. Diversas construções solúveis de PelD foram clonadas e expressas, sendo que a construção compreendendo os resíduos 176-455 (PelD176-455) foi cristalizada com sucesso e teve sua estrutura determinada por iodo-SAD. O modelo final apresentou os dois domínios com enovelamentos característicos das famílias GAF e GGDEF, sendo a interface inter-domínios composta majoritariamente por resíduos hidrofóbicos. Visando uma compreensão das bases moleculares de reconhecimento e ativação de PelD por c-di-GMP, uma estrutura em complexo com o ligante foi resolvida. Como esperado, o dinucleotídeo foi encontrado no sítio inibitório do domínio GGDEF, onde o motivo R367xxD370 e o resíduo R402 são responsáveis pela maior parte das interações com c-di-GMP. No entanto, nenhuma grande mudança estrutural foi observada entre as formas apo e holo de PelD, ao contrário de outros sistemas efetores tal como LapD e domínios PilZ. Curiosamente, apenas uma molécula de c-di-GMP foi encontrada no sítio, contrastando com a forma dimérica intercalada normalmente ligada aos sítios inibitórios de domínios GGDEF, tais como em PleD e WspR. Estudos de ITC confirmaram a estequiometria 1:1 em solução. Isso mostra a versatilidade dos diversos receptores já identificados até o momento, frente à ligação desse dinucleotídeo. Estudos de bioinformática identificaram uma potencial região de coiled-coil na hélice juxtamembrana de PelD, resíduos 115-160, provavelmente responsável pela homodimerização. Visando uma comprovação experimental dessa hipótese, uma construção contendo toda a porção citoplasmática, PelD111-455, foi expressa e purificada. Estudos comparativos de dicroísmo circular e ultracentrifugação analítica entre as construções PelD176-455 e PelD111-455 realmente demonstraram que os resíduos extras presentes em PelD111-455 formam uma hélice-α e são responsáveis pela dimerização da porção citoplasmática da proteína. De modo geral, os resultados aqui apresentados não só contribuirão para o entendimento dos mecanismos de regulação das vias de sinalização mediadas por c-di-GMP como, em longo prazo, poderão levar ao desenvolvimento de agentes contra infecções bacterianas. / Microorganisms may be presented either in planktonic free-swimming life-style or adhered to surfaces, forming a complex and dynamic community known as biofilm. In recent years, with the progress of research at the molecular level, it was identified that the majority of bacteria use guanosine monophosphate (3\'-5 \')-cyclic dimeric (c-di-GMP) as a second messenger. Generally, this molecule controls the cell signaling, virulence, communication between cells and expression of proteins related to the phenotype of biofilms in response to its intracellular concentration. Its synthesis and degradation are controlled respectively by diguanylate cyclases (DGC) containing the GGDEF domain and phosphodiesterases (PDE) with the domains EAL or HD-GYP. In Pseudomonas aeruginosa (PA14) a novel class of receptor specific for c-di-GMP has been identified, the transmembrane protein PelD, which contains a GAF and degenerate GGDEF domains in the cytoplasmic portion. Its modulation through this dinucleotide controls the production of exopolysaccharides by the components of the conserved operon pel and directly influences the ability of biofilm formation. Due to the paucity of data about the molecular events of the signaling mechanism mediated by c-di-GMP, this study aimed to characterize biophysically and structurally the protein PelD. Various soluble constructions of PelD were cloned and expressed, and the construction comprising the residues 176-455 (PelD176-455) was successfully crystallized and its structure was determined by iodine-SAD. The final model showed the two characteristic domains of families GAF and GGDEF, and the inter-domain interface composed primarily of hydrophobic residues. Seeking an understanding of the molecular basis of recognition and activation of PelD by c-di-GMP, a structure in complex with the ligand was solved. As expected, the dinucleotide was found at the inhibitory site of the GGDEF domain, where the motif R367xxD370 and the residue R402 are responsible for most of the interactions with c-di-GMP. However, no major structural change was observed between the apo and holo forms of PelD, unlike other effector systems such as LapD and domains PilZ. Interestingly, only one molecule of c-di-GMP was present on the site, in contrast to the dimeric intercalated form normally found at I-sites GGDEF domains, such as PleD and in WspR. ITC studies confirmed the 1:1 stoichiometry in solution. This shows the versatility of the various receptors identified so far, compared to the binding of dinucleotide. Bioinformatics studies have identified a potential coiled-coil region in the juxtamembrane helix of PelD, residues 115-160, probably responsible for homodimerization. Aiming at an experimental confirmation of this hypothesis, a construct containing the full cytoplasmic portion, PelD111-455 was expressed and purified. Comparative studies of circular dichroism and analytical ultracentrifugation between constructs PelD176-455 and PelD111-455 indeed demonstrated that the extra residues present in PelD111-455 form an α-helix and are responsible for dimerization of the cytoplasmic portion of the protein. Overall, the results presented here not only contribute to the understanding of the mechanisms of regulation of signaling pathways mediated by c-di-GMP as in the long run, may lead to the development of agents against bacterial infections.

論文(哲學碩士)--香港中文大學硏究院歷史學部,1994. / 參考文獻: leaves 1-14 (last group) / [馬木池]. / 圖表索引 / 前言 / Chapter 第一章 --- 清前期潮州地區書院的發展 / Chapter (一） --- 書院的廢毀時期--順治元年至康熙二〇年 / Chapter (二) --- 書院的恢復期--康、雍時期 / Chapter (三） --- 書院發展的高峰期--乾隆時期 / Chapter (四) --- 書院發展的沉寂期--嘉、道、咸時期 / Chapter 第二章 --- 清前期潮州地方社會與書院發展的關係 / Chapter (一） --- 清前期潮州地方社會問題 / Chapter (二） --- 清前期地方官治潮政策分析 / Chapter 第三章 --- 清前期地方官與書院 / Chapter (一） --- 地方官與書院的興修 / Chapter (二） --- 地方官與書院經費 / Chapter (三） --- 地方官與書院的運作 / Chapter 第四章 --- 清前期地方士紳與書院 / Chapter (一） --- 清初潮州地區推廣「官話」政策的成敗--以潮籍為主的書院院長 / Chapter (二） --- 書院院長與地方社會 / 總結 / 參考書目

Francesco di Marco Datini (c. 1335-1410) left his native city of Prato, near Florence, in about 1350 to become a successful merchant in Avignon, France. He returned three decades later to decorate his newly built private residence in the historic center of Prato. Under his patronage, frescoes of sacred and secular subject matter were executed in the residence from 1389-95. The artists that have been concretely identified, or suggested, as working in the Palazzo Datini include: Arrigo di Niccolò, from Prato; minor painters Dino di Puccio, Jacopo d’Agnolo, and Agnolo; Florentine artists Tommaso del Mazza, Bartolomeo di Bertozzo, and Pagolino d’Ugolino; and the master artists Niccolò di Pietro Gerini and Agnolo Gaddi. Many of the original frescoes were uncovered during renovations of the 1950s. Those in the entry hall and ground floor rooms survive in varied condition. This recovery is significant because the survival of large scale private works of this kind in Italy is rare. Datini’s legacy also comprises hundreds of ledgers, account books, and thousands of personal and business letters dating from 1363 to 1410. These are now contained in the Archivio Storico di Prato. Using the surviving visual and written material as a reference point, this thesis examines the contexts behind Datini’s choices as patron. In particular, the influence of predominant values in merchant culture will be considered. The frescoes are explored in comparison with the interior decoration in the palaces of contemporaries. Precedence is given to residences in Florence and other urban centers in Tuscany. Related paintings from Avignon are also considered, as Datini lived there for many years. Visual parallels can also be drawn between the Datini frescoes and manuscript illuminations, among other sources. The murals were influenced by Datini’s own interests, larger cultural values, and the painters, who derived from the Florentine tradition. This thesis seeks to examine the cultural and artistic environment in late Trecento Prato, Datini’s contact with the artists, the subject matter and style of the frescoes, and their reception. / Thesis (Master, Art History) -- Queen's University, 2010-10-25 16:44:10.326

This thesis is an exploration of the chapters of Francesco Di Giorgio's Trattati di Architettura, Ingegneria e Arte Militare, that pertain to mechanical devices. While it is difficult to imagine actually constructing Di Giorgio's machines from the drawings and descriptions in his treatises, given their apparent inefficiencies and ambiguities, the Aristotelean science and philosophy referenced throughout the Trattati provides a basis for looking at them as demonstrations of concepts beyond their immediate applications for architecture and engineering. By considering these devices in Di Giorgio's own terms, terms suggested by his own experiences, as well as his writings and paintings, strong associations can be made to the science, philosophy and the theology of his time.

La ricerca si occupa delle riforme relative alla formazione dei docenti peruviani dal 1821 ad oggi, con particolare attenzione ai processi di accreditamento delle facoltà di educazione. Il primo capitolo percorre la formazione dei docenti dall'inizio della Repubblica fino agli anni '90, per soffermarsi sui recenti programmi di formazione e aggiornamento dei docenti in attività. Il secondo capitolo presenta una visione sintetica dei sistemi di accreditamento latinoamericani, in particolare dei quattro paesi di riferimento per il Perù (Brasile, Argentina, Cile, Colombia). Approfondisce poi il sistema di accreditamento peruviano dalle origini fino alla legge 30220 (2014). Il terzo capitolo analizza con maggiore profondità l'accreditamento peruviano dei corsi di,laurea di educazione-pedagogia e conclude con rilievi critici e proposte di miglioramento del modello. La tesi sostiene che fissare l'attenzione sulla formazione iniziale del docente (qualità dei corsi di laurea) è fondamentale per ogni riforma dell'educazione. In questo processo l'accreditamento richiede un dibattito più approfondito con il coinvolgimento delle facoltà di pedagogia-educazione e l'impegno da parte loro nella preparazione dei futuri esperti della valutazione e accreditamento. / The research dials with the reform of the Peruvian teacher formation from 1821 until today, with particular attention to the process of accreditation of education faculties. The first chapter investigates the training of teachers since the beginning of the Republic until the 90 to stop at the recent upgrade programs and of teachers training in activity. The second chapter presents a synthesis of Latin American accreditation systems, in particular for countries relating to Peru (Brazil, Argentina, Chile, and Colombia). Then deepens the Peruvian accreditation system from its origins to the law 30220 (2014). The third chapter examines more closely the Peruvian accreditation of the education careers and concludes with critical comments and suggestions for improvement of the current model. The thesis states that for any education reform is essential to focus attention on initial teacher training (quality of racing). It is also necessary to a wider debate on accreditation with greater commitment of further education colleges should care for the training of future experts for evaluation and accreditation

Univ., Diss.--Zürich, 2002.

Univ., Diss.--Fribourg, 2002.

Diss.--Philosophie--Denton, Tex.--North Texas state university, 1968. / Bibliogr. f. 313-330 (t.1). Index.

Th.--Sci.--Bordeaux 1, 1979. N°: 632.

En 1955, Luciano Berio obtient de la R.A.I. l’autorisation de créer, dans les locaux milanais de la radio, le Studio di Fonologia, premier studio européen mêlant musique concrète et musique électronique. Ce lieu, dont il définira tout autant les statuts que les différents appareillages, va devenir pour lui durant six ans un lieu de production effrénée de radiodrames pour la R.A.I., mais également un laboratoire de recherches personnelles. Entouré par un cercle d’avant-garde, très au fait des publications scientifiques de son temps - notamment dans le domaine de la linguistique, de la théorie musicale, et du structuralisme - il va plonger de façon empirique au cœur la matière vocale. La situation acousmatique du studio, l’absence d’interprètes, la dimension poétique et théâtrale du langage vont l’amener à se questionner sur l’écoute, et, dans une pensée brechtienne, sur l’écoute de l’écoute. Nous tentons de dégager, dans notre travail, en partant de la réalité du travail en studio, les éléments qui ultérieurement ont fusionné pour devenir le style bérien et qui sont déjà en germe ou même parfaitement identifiables durant cette période qui va de Chamber Music à Laborintus II. / In 1955 the R.A.I. granted Luciano Berio permission to create the Studio di Fonologia in their Milan radio studios, the first European studio to combine “musique concrète” and purely electronic music. He was able to choose the equipment and define the usage of the studio so that it became a place where he would produce radio dramas for the R.A.I. at a furious pace for six years as well as a laboratory for personal research. Surrounded by a circle of avant-garde personalities, very aware of scientific publications of his time - notably in the domains of linguistics, musical theory and structuralism - he will dive in an empirical way into the heart of vocal material. The acousmatic nature of the studio, the absence of live performers, and the poetic and theatrical dimension of language will lead him to ask himself about the notion of listening, and in a Brechtian way, about listening to listening. We will attempt in our work to reveal - from his actual studio work - the elements which later merged to become the Berian style and which were already germinating or even perfectly recognizable during the period from Chamber Music to Laborintus II.