Tautomerism and Fragmentation of Biologically Active Hetero Atom (O, N)-Containing Acyclic and Cyclic Compounds Under Electron Ionization

In this thesis a total of 86 compounds containing the hetero atoms oxygen and nitrogen were studied under electron ionization mass spectrometry (EIMS). These compounds are biologically active and were synthesized by various research groups. The main attention of this study was paid on the fragmentations related to different tautomeric forms of 2- phenacylpyridines, 2-phenacylquinolines, 8-aryl-3,4-dioxo-2H,8H-6,7-dihydroimidazo- [2,1-c][1,2,4]triazines and aryl- and benzyl-substituted 2,3-dihydroimidazo[1,2-a]pyrimidine-5,7-(1H,6H)-diones. Also regio/stereospecific effects on fragmentations of pyrrolo- and isoindoloquinazolinones and naphthoxazine, naphthpyrrolo-oxazinone and naphthoxazino-benzoxazine derivatives were screened. Results were compared with NMR data, when available. The first part of thesis consists of theory and literature review of different types of tautomerism and fragmentation mechanisms in EIMS. The effects of tautomerism in biological systems are also briefly reviewed. In the second part of the thesis the own results of the author, based on six publications,are discussed. For 2-phenacylpyridines and 2-phenacylquinolines the correlation of different Hammett substituent constants to the relative abundances (RA) or total ion currents (% TIC) of selected ions were investigated. Although it was not possible to assign most of the ions formed unambiguously to the different tautomers, the linear fits of their RAs and % TICs can be related to changing contributions of different tautomeric forms. For dioxoimidazotriazines and imidazopyrimidinediones the effects of substituents were rather weak. The fragmentations were also found useful for obtaining structural information. Some stereoisomeric pairs of pyrrolo- and isoindoloquinazolines and regiomeric pairs of naphtoxazine derivatives showed clear differences in thir mass spectra. Some mechanisms are suggested for their fragmentations.

Hidrogenação de compostos orgânicos utilizando método eletroquímico para geração de hidrogênio in situ: hidrogenação eletrocatalítica

Electrocatalytic hydrogenation (HEC) may be compared to catalytic hydrogenation (HC). The difference between these methods is the hydrogen source: HC needs a hydrogen gas supply; HEC needs a source of protons (solvent) to be reduced at a cathode surface. HEC has presented interesting advances in the last decades due to investigation of the influence of the supporting electrolyte, co-solvent, surfactant, presence of inert gas and the composition of the electrode on the reaction. Several classes of organic compounds have been hydrogenated through HEC: olefins, ketones, aldehydes, aromatics, polyaromatics and nitro-compounds. This paper shows some details about the HEC which may be regarded as a promising technique for the hydrogenation of organic compounds both in industrial processes and in laboratories.

Improving the oscillating grid method to characterize aquaculture biosolids using a laser beam and image analysis

Quickremovalofbiosolidsinaquaculturefacilities,andspeciallyinrecirculatingaquaculturesystems(RAS),isoneofthemostimportantstepinwastemanagement.Sedimentationdynamicsofbiosolidsinanaquaculturetankwilldeterminetheiraccumulationatthebottomofthetank.

Therapeutic Properties of Superoxide Dismutase 3 and Mesenchymal Stromal Cells in Peripheral Ischemia

The aim of this study was to characterize the cellular mechanisms leading to the beneficial effect of anti-oxidative gene therapy and pro-angiogenic stem cell therapy in acute peripheral ischemia. Post-ischemic events aim to re-establish tissue blood perfusion, to clear cellular debris, and to regenerate lost tissue by differentiation of satellite cells into myoblasts. Although leukocytes have an essential role in clearing cellular debris and promoting angiogenesis, they also contribute to tissue injury through excessive ROS production. First, we investigated the therapeutic properties of extracellular superoxide dismutase (SOD3) gene transfer. SOD3 was shown to reduce oxidative stress, to normalize glucose metabolism, and to enhance cell proliferation in the ischemic muscle. Analysis of the mitogenic Ras-Erk1/2 pathway showed SOD3 mediated induction offering a plausible explanation for enhanced cell proliferation. In addition, SOD3 reduced NF-κB activity by enhancing IκBα expression thus leading to reduced expression of inflammatory cytokines and adhesion molecules with consequent reduction in macrophage infiltration. Secondly, we sought to determine the fate and the effect of locally transplanted mesenchymal stem/stromal cells (MSCs) in acute ischemia. We showed that a vast majority of the transplanted cells are cleared from the injury site within 24 hours after local transplantation. Despite rapid clearance, transplantation was able to temporarily promote angiogenesis and cell proliferation in the muscle. Lack of graft-derived growth factor expression suggests other than secretory function to mediate this observed effect. In conclusion, both SOD3 and MSCs could be utilized to alleviate peripheral ischemia induced tissue injury. We have described a previously unidentified growth regulatory role for SOD3, and suggest a novel mechanism whereby transplanted MSCs enhance the reparative potential of the recipient tissue through physical contacts.

A SKETCH ON NĀGĀRJUNA'S PERSPECTIVES ON "RELATION"

ABSTRACT The aim of this paper is to provide a sketch on the way Nāgārjuna deals with the idea of 'relation'. The concept of 'relation' as expressed in the Pāli sources is here theoretically systematized according to three patterns: 1. (onto)logical, 2. strictly subordinative existential, 3. non-strictly subordinative existential. After having discussed Nāgārjuna's acceptance and treatment of these three patterns, particular attention is paid to the non-strictly subordinative existential relation. This kind of relation is meant to describe the way the factors of the conditioned co-origination are linked to each other and is exemplified by Nāgārjuna by means of the father-son bond. A possible way to explain the conditioned co-origination doctrine in the light of the father-son example is here suggested by having resource to the 'Cambridge change' theory. Even if in the Pāli Canon the non-strictly subordinative existential pattern is said to apply to all the other factors of the conditioned co-origination, there is no direct evidence that it concerns also the avidyā-saṃskāras link. It will be shown how Nāgārjuna, by applying it to the avidyā-saṃskāras link, seems to introduce a new perspective in the conditioned co-origination theory.

Anchor or Accelerate – A Study on Cancer Cell Adhesion and Motility

Cell migration and adhesion to the extracellular matrix (ECM) are crucial in many biological and pathological processes such as morphogenesis, tissue repair, inflammatory responses, survival, and cancer. Cell-matrix adhesion is mediated by the integrin family of transmembrane receptors, which not only anchor cells to their surroundings, but also transmit bidirectional signalling at the cell surface and couple the ECM to the cytoskeleton. Another group of adhesion receptors are the syndecan proteoglycans, which engage the ECM and possess signalling activity in response to a variety of ligands. Cell migration is a complex process that requires spatial and temporal coordination of adhesion, cell contractility, intracellular traffic of integrins, and matrix turnover by matrix metalloproteinases (MMPs). Thus, integrins and syndecans, as well as MMPs, play essential roles in cancer cell migration and invasion. The understanding of the cooperation of syndecans and integrins was broadened in this thesis study. The results reveal that syndecan-1 functions in concert with 21 integrin in cell adhesion to collagen, whereas syndecan-4 is essential in 21 integrin-mediated matrix contraction. Finally, oncogenic K-Ras was shown to regulate 21 integrin, membrane-type 1 MMP, and syndecan-1 and -4 expression and their cooperation in cell invasion. Epithelial-mesenchymal transition (EMT) is fundamental during embryogenesis and organ development. Activation of EMT processes, including the upregulation of mesenchymal intermediate filament protein vimentin, has also been implicated in the acquisition of a malignant phenotype by epithelial cancer cells. Members of the protein kinase C (PKC) superfamily are involved in cell migration and various integrindependent cellular functions. One aim of this work was to shed light on the role of vimentin in the regulation of integrin traffic and cell motility. In addition, the mechanism by which vimentin participates in EMT was investigated. The results show that integrin recycling and motility are dependent on the PKC–mediated phosphorylation of vimentin. In addition, vimentin was found to be a positive regulator of EMT and regulate the expression of several migratory genes. Specifically, vimentin governs the expression of receptor tyrosine kinase Axl, which is implicated in tumour growth and metastasis. Taken together, the findings described in this thesis reveal novel aspects of the complex interplay between distinct cellular components: integrins, syndecans, and the vimentin cytoskeleton, which all contribute to the regulation of human cancer cell adhesion, migration, and invasion.

Pluralité et fluidité antinormatives : étude sur les transgressions sexuelles dans l’oeuvre romanesque de Marguerite Yourcenar

Avhandlingen är en studie i kön, genus och sexualitet i den franska författarinnan Marguerite Yourcenars romaner. Undersökningen utgår från ett queer-teoretiskt perspektiv och har som syfte att belysa de olika sätt på vilka Yourcenars texter uttrycker ett ifrågasättande av och ett överskridande av normer beträffande kön, manlighet och kvinnlighet, samt sexuella kategorier. Det tudelade könssystemet (man/kvinna) och motsättningen mellan heterosexualitet och homosexualitet ses som förenklade sociala konstruktioner som inte motsvarar den mångfasetterade verklighet som avbildas i texterna. Mångfald, flyktighet och gränsöverskridande är nyckelord i undersökningen. I avhandlingen granskas snart när alla Yourcenars romaner samt en novell i form av separata läsningar, för att ge en så heltäckande bild som möjligt av hur problematiken behandlas i hennes produktion. Således belyses särarten hos varje verk och det är även möjligt att uppmärksamma den utveckling som skett under karriärens gång. Kön och sexualitet diskuteras separat i enlighet med Gayle Rubins och Eve Sedgwicks tes att sexualitetsforskning och genusstudier inte bör sammanblandas: sexualitet är ett så komplext fenomen att kön och genus är otillräckliga analysverktyg för en seriös och djuplodande diskussion. Genom att lyfta fram olika exempel på figurer i Yourcenars romaner som implicit eller explicit tar avstånd ifrån en klar indelning i män och kvinnor, respektive manlighet och kvinnlighet, påvisas att tanken att det existerar två olika biologiska kön systematiskt tillbakavisas. Diskussionen om sexualitetstemat koncentrerar sig på förhållandet mellan homo-och heterosexualitet, men betonar även hur temat anknyter till andra centrala teman, såsom religion och ras. Bilden av homosexualitet ändrar från en text till en annan, vilket illusterar att en skarp motsättning mellan homo- och heterosexualitet är ohållbar.

A Educação Médica entre mapas e âncoras: a aprendizagem significativa de David Ausubel, em busca da Arca Perdida

O processo de aprendizagem tem motivado, desde a Antigüidade, intensos debates. Dentre as diferentes teorias propostas tem ganho relevância, nos séculos XX e XXI, a concepção cognitivista de David Ausubel, na qual se assume que os mecanismos do aprender são mais eficientes em situações nas quais o estudante consegue, utilizando conhecimentos prévios, agregar e incorporar significado aos novos conteúdos, evitando-se, assim, que esse conhecimento recém-incorporado seja armazenado, por meio de associações ineptas, à estrutura cognitiva. No âmbito da educação médica, diante das imperiosas mudanças necessárias para a formação de um profissional que aprenda a aprender, a aprendizagem significativa permite uma genuína contextualização dos conhecimentos necessários à prática médica, facultando, portanto, um aprendizado mais efetivo e permitindo a atuação em um contexto complexo e interdisciplinar. Em conformidade com o exposto, o presente manuscrito objetiva apresentar a teoria da aprendizagem significativa, discutindo elementos da incorporação deste conceito à educação médica.

Ecologia na formação do profissional de saúde: promoção do exercício da cidadania e reflexão crítica comprometida com a existência

Este manuscrito, baseado em revisão de literatura, convida à reflexão sobre a importância da discussão das questões ecológicas na formação do profissional de saúde. Entre os aspectos considerados fundamentais, inclui-se a revisão da Agenda 21 e as interações entre os processos produtivos, o consumo, as inovações tecnológicas e a degradação da saúde e do meio ambiente. A proposta central desta discussão é a sensibilização para incorporar o debate sobre a relação entre ambiente e saúde nos currículos dos diversos cursos da área da saúde, incluindo graduação e pós-graduação. Considera-se que essas reflexões no espaço acadêmico são formas potenciais de promover a responsabilização dos futuros profissionais de saúde no exercício da cidadania, destacando o comprometimento presente e futuro com a existência e com as condições e a qualidade de vida dos indivíduos, da sociedade e do planeta.

Transição paradigmática na educação médica: um olhar construtivista dirigido à aprendizagem baseada em problemas

A necessidade de mudança no projeto político-pedagógico das escolas médicas vem sendo discutida, especialmente, em resposta ao amadurecimento da reflexão acerca do perfil do egresso desejado. Reconhece- se que o ensino médico tradicional - centrado, prioritariamente, na transmissão de conhecimentos - tem levado à formação de profissionais despreparados para responder aos agravos à saúde mais encontrados na população. Para tentar mudar esse panorama, vêm sendo privilegiadas, a partir das Diretrizes Curriculares Nacionais do Curso de Graduação em Medicina do Ministério da Educação (MEC), as metodologias ativas de ensino-aprendizagem, entre as quais se destaca a Aprendizagem Baseada em Problemas (ABP), que permite maior participação do estudante na construção do conhecimento. Tal encaminhamento é realizado a partir da inclusão do graduando na comunidade desde os primeiros períodos do curso médico, promovendo a contextualização dos constructos teóricos adquiridos por meio de buscas individuais e do compartilhamento do conhecimento. Desta forma, cria-se uma parceria entre instituições de ensino superior, serviços de saúde e a comunidade, a partir da qual se espera formar médicos com uma visão integral do ser humano, comprometidos com a sociedade.

D’abord, ensuite, enfin et 0, De plus: Organisation textuelle par des séries linéaires dans les articles de recherche

The study examines the signalling of text organisation in research articles (RA) in French. The work concentrates on a particular type of organisation provided by text sequences, i.e. structures organising text to items of which at least some are signalled by markers of addition or order: First… 0… The third point… In addition… / Premièrement… 0… Le troisième point… De plus… By indicating the way the text is organised, these structures guide the reader in the reading process so that he doesn’t need to interpret the text structure himself. The aim of the work is to study factors affecting the marking of text sequences. Why is their structure sometimes signalled explicitly by markers such as secondly, whereas in other places such markers are not used? The corpus is manually XML-annotated and consists of 90 RAs (~800 000 words) in French from the fields of linguistics, education and history. The analysis highlights several factors affecting the marking of text sequences. First, exact markers (such as fist ) seem to be more frequent in sequences where all the items are explicitly signalled by a marker, whereas additive markers (such as moreover) are used in sequences with both explicitly signalled and unmarked items. The marking of explicitly signalled sequences seems thus to be precise and even repetitive, whereas the signalling of sequences with unmarked items is altogether more vague. Second, the marking of text sequences seems to depend on the length of the text. The longer the text segment, the more vague the marking. Additive markers and unmarked items are more frequent in longer sequences possibly covering several pages, whereas shorter sequences are often signalled explicitly by exact markers. Also the marker types vary according to the sequence length. Anaphoric expressions, such as first, are fairly close to their referents and are used in short sequences, connectors, such as secondly, are frequently used in sequences of intermediate length, whereas the longest sequences are often signalled by constructions composed of an ordinal and a noun acting as a subject of the sentence: The first item is… Finally, the marking of text organisation depends also on the discipline the RA belongs to. In linguistics, the marking is fairly frequent and precise; exact markers such as second are the most used, and structures with unmarked items are less common. Similarly, the marking is fairly frequent in education. In this field, however, it is also less precise than in linguistics, with frequent unmarked items and additive markers. History, on the other hand, is characterised by less frequent marking. In addition, when used, the marking in this field is also less precise and less explicit.

Atributos químicos de um cambissolo e crescimento de mudas de eucalipto após adição de lodo de curtume contendo cromo

O processo de curtimento do couro gera resíduos com potencial de uso como corretivo e fertilizante, no entanto alguns de seus constituintes são tóxicos quando presentes em elevado teor no solo, o que limita sua utilização nos sistemas de produção. O objetivo deste trabalho foi avaliar as alterações nos atributos químicos de um Cambissolo Húmico e o crescimento e teor de Cr em clones de Eucalyptus urophylla após a adição de doses de lodo de curtume (LCT). O experimento foi realizado em casa de vegetação, no período de março a julho de 2009. Os tratamentos consistiram da adição de doses de lodo de curtume (0; 1,5; 3,0; 4,5; e 6,0 g dm-3) ao solo, que recebeu, de forma complementar, calcário e adubação NPK em dose única. O pH, a condutividade elétrica, a relação de adsorção de sódio e a porcentagem de sódio trocável, relacionadas com a salinidade do solo, aumentaram com o incremento das doses do lodo de curtume, porém os valores observados ficaram abaixo dos níveis salinos. O teor de Cr solúvel no solo, extraído pela água, decresceu linearmente com o aumento das doses de LCT, correlacionando-se negativamente com o pH do solo. O aumento da dose do LCT proporcionou incremento na altura dos clones de Eucalyptus urophylla em até 11,5% em relação à testemunha. A produção de massa das raízes secas decresceu, em média, 28,3%, em relação à testemunha, com a maior dose (6 g dm-3). As plantas de eucalipto, em todos os tratamentos, continham o Cr somente no sistema radicular, e, quanto maior a dose de LCT, maior o teor desse metal nas raízes.

Impacto da irrigação sobre os solos de perímetros irrigados na Bacia do Acaraú, Ceará, Brasil

Para avaliar o risco de salinidade e de sodicidade do solo pelo manejo da irrigação, desenvolveu-se estudo comparativo entre os valores de CEes e RAS de área irrigada com os da mata nativa. A investigação ocorreu nos Distritos Irrigados Baixo Acaraú (DIBAU) e Araras Norte (DIPAN), localizados na Bacia do Acaraú. As amostras de solo foram coletadas bimestralmente, de maio/2003 a set./2005, nas camadas de 0-0,30 m; 0,30-0,60 m; 0,60-0,90 m e 0,90-1,20 m, sendo as análises efetuadas no Laboratório de Solo e Água da Embrapa Agroindústria Tropical. Para identificar se os incrementos dos parâmetros estudados eram estatisticamente significativos, aplicou-se o teste de Wilcoxon. Os incrementos de CEes foram maiores no DIPAN, com média de 250%, enquanto no DIBAU, a média atingiu 50%. Em 2004, as precipitações pluviométricas levaram a área irrigada do DIBAU à condição de mata nativa, não ocorrendo o mesmo no DIPAN. Para a RAS, os incrementos médios situaram-se em torno de 200% (DIBAU) e não houve incremento no DIPAN. Portanto, os solos do DIBAU apresentaram maior predisposição à sodicidade, e os do DIPAN, maior risco de salinização. Apesar dos incrementos, os valores da CEes e RAS apresentaram-se inferiores ao limite de classificação de solos salinos e sódicos, respectivamente. No DIBAU, a chuva teve maior influência no processo de lixiviação devido à predominância da textura arenosa dos solos.

Segregation of powder mixtures in silos with particular reference to dry mineral-based construction materials

Segregering eller segregation är ett fenomen som kan förekomma inom olika områden av samhället. Inom samhällsvetenskaperna kan segregering definieras som det rumsliga åtskiljandet av befolkningsgrupper på urval av ras eller etniskt ursprung, kön, social härkomst, religion, ålder, yrke, osv. Segregering av befolkningsgrupper sker ofta mer eller mindre frivilligt och är motsatsen till integration. Inom partikelteknologi definieras segregering oftast som det rumsliga åtskiljandet av beståndsdelarna i en blandning av olika partiklar. Segregering sker då på urval av bl.a. partiklarnas storlek, densitet, form, elektrostatiska eller mekaniska egenskaper, och kan beskrivas som motsatsen till blandning. Segregeringsmekanismer används för att förklara hur och varför en partikelblandning segregerar samt vad slutresultatet i form av den rumsliga fördelningen av partiklarna blir till följd av att blandningen utsetts för en viss behandling. I denna avhandling har segregering av partikelblandningar och speciellt torra mineralbaserade byggmaterial (t.ex. murbruk) till följd av lagring i siloer studerats. Vid industriell produktion av mineralbaserade byggmaterial används siloer för korttidslagring av slutprodukterna precis innan förpackning. Segregering leder till kraftiga variationer i sammansättningen för partikelströmmen ut ur silon, vilket gör att slutprodukterna inte uppfyller kvalitetskraven och kan därmed inte säljas till kunder. Detta leder till arbetsam och dyr bearbetning (återcirkulation) av produkterna med påföljder för produktionsekonomin samt hållbara utvecklingen. I avhandlingen identifierades de väsentligaste segregeringsmekanismerna för torra mineralbaserade byggmaterial i siloer. Dessutom klargjordes effekterna av materialegenskaper, processbetingelser och siloparametrar. Slutligen behandlas möjliga åtgärder för minskning av partikelsegregering i siloer samt tillämpning av matematiska metoder för simulering av partikelflöden med hjälp av datorer.