No description available.

The theme of this thesis is syntax analysis of the source texts based on TeX. The work contains the summary of basic terms from the theory of formal languages, there is also explained the function of the translator in all the analytical phases of the translation and finally it contains the introduction of the Lua scripting language and the ConTeXt typesetting system. The aim of the thesis is implementation of the syntax analyser for the source texts in ConTEXt format. The implementation is accompanied by the description of the solution developement of the lexical analysis, syntax analysis, creating syntax diagrams and context-free grammar.

abstract: The communication of genetic material with biomolecules has been a major interest in cancer biology research for decades. Among its different levels of involvement, DNA is known to be a target of several antitumor agents. Additionally, tissue specific interaction between macromolecules such as proteins and structurally important regions of DNA has been reported to define the onset of certain types of cancers. Illustrated in Chapter 1 is the general history of research on the interaction of DNA and anticancer drugs, most importantly different congener of bleomycin (BLM). Additionally, several synthetic analogues of bleomycin, including the structural components and functionalities, are discussed. Chapter 2 describes a new approach to study the double-strand DNA lesion caused by antitumor drug bleomycin. The hairpin DNA library used in this study displays numerous cleavage sites demonstrating the versatility of bleomycin interaction with DNA. Interestingly, some of those cleavage sites suggest a novel mechanism of bleomycin interaction, which has not been reported before. Cytidine methylation has generally been found to decrease site-specific cleavage of DNA by BLM, possibly due to structural change and subsequent reduced bleomycin-mediated recognition of DNA. As illustrated in Chapter 3, three hairpin DNAs known to be strongly bound by bleomycin, and their methylated counterparts, were used to study the dynamics of bleomycin-induced degradation of DNAs in cancer cells. Interestingly, cytidine methylation on one of the DNAs has also shown a major shift in the intensity of bleomycin induced double-strand DNA cleavage pattern, which is known to be a more potent form of bleomycin induced cleavages. DNA secondary structures are known to play important roles in gene regulation. Chapter 4 demonstrates a structural change of the BCL2 promoter element as a result of its dynamic interaction with the individual domains of hnRNP LL, which is essential to facilitate the transcription of BCL2. Furthermore, an in vitro protein synthesis technique has been employed to study the dynamic interaction between protein domains and the i-motif DNA within the promoter element. Several constructs were made involving replacement of a single amino acid with a fluorescent analogue, and these were used to study FRET between domain 1 and the i-motif, the later of which harbored a fluorescent acceptor nucleotide analogue. / Dissertation/Thesis / Doctoral Dissertation Chemistry 2014

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-04-02T12:19:53Z No. of bitstreams: 1 CiroMoraisMedeiros_DISSERT.pdf: 4866075 bytes, checksum: 12574ac5a6867ff73a1dc45a5ef78478 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-04-04T11:51:20Z (GMT) No. of bitstreams: 1 CiroMoraisMedeiros_DISSERT.pdf: 4866075 bytes, checksum: 12574ac5a6867ff73a1dc45a5ef78478 (MD5) / Made available in DSpace on 2018-04-04T11:51:20Z (GMT). No. of bitstreams: 1 CiroMoraisMedeiros_DISSERT.pdf: 4866075 bytes, checksum: 12574ac5a6867ff73a1dc45a5ef78478 (MD5) Previous issue date: 2018-02-23 / A internet possibilitou a cria??o de um imenso espa?o de dados global, que pode ser acessado na forma de p?ginas web. Entretanto, p?ginas web s?o ideais para apresentar conte?do para seres humanos, mas n?o para serem interpretadas por m?quinas. Al?m disso, se torna dif?cil relacionar as informa??es armazenadas nos bancos de dados por tr?s dessas p?ginas. Para contornar esses problemas foi desenvolvido o Linked Data, um conjunto de boas pr?ticas para relacionamento e publica??o de dados. O formato padr?o recomendado pelo Linked Data para armazenamento e publica??o de dados relacionados ? o Resource Description Framework (RDF). Este formato utiliza triplas na forma (sujeito, predicado, objeto) para estabelecer relacionamentos entre os dados. Um banco de dados de triplas pode ser facilmente visualizado como um grafo, de maneira que as consultas s?o feitas por meio da defini??o de caminhos no grafo. SPARQL, a linguagem padr?o para consultas em grafos RDF, possibilita a defini??o de caminhos utilizando express?es regulares. Entretanto, express?es regulares t?m expressividade reduzida, insuficiente para algumas consultas desej?veis. Para contornar este problema, alguns trabalhos propuseram a utiliza??o de gram?ticas livres-de-contexto para definir os caminhos. Desenvolvemos um algoritmo para avalia??o de consultas de caminhos livres-de-contexto em grafos inspirado em t?cnicas de parsing top-down. Dado um grafo e uma consulta definida com base em uma gram?tica livre-de-contexto, nosso algoritmo identifica pares de v?rtices ligados por caminhos que formam palavras pertencentes ? linguagem gerada pela gram?tica. Argumentamos que nosso algoritmo ? correto e demonstramos outras propriedades importantes. O algoritmo apresenta complexidade c?bica de tempo de execu??o no pior caso em termos do n?mero de v?rtices no grafo. Implementamos o algoritmo proposto e avaliamos seu desempenho com bancos de dados RDF e com grafos sint?ticos para confirmar sua efici?ncia. / The internet has enabled the creation of an immense global data space, that may be accessed in the form of web pages. However, web pages are ideal for presenting content to human beings, but not to be interpreted by machines. In addition, it becomes difficult to relate the information stored in the databases behind these pages. To overcome those problems, the Linked Data was developed as a set of good practices for relating and publishing data. The standard format recommended by Linked Data for storing and publishing related data is RDF. This format uses triples in the form (subject, predicate, object) to stabilish relationships between the data. A triplestore can be easily visualized as a graph, so queries are made by defining paths in the graph. SPARQL, the standard query language for RDF graphs, supports the definition of paths using regular expressions. However, regular expressions have reduced expressiveness, insufficient for some desirable queries. In order to overcome this problem, some studies have proposed the use of context-free grammars to define the paths. We present an algorithm for evaluating context-free path queries in graphs inspired by top-down parsing techniques. Given a graph and a query defined over a contextfree grammar, our algorithm identifies pairs of vertices linked by paths that form words of the language generated by the grammar. We argue that our algorithm is correct and demonstrate other important properties of it. It presents cubic worst-case runtime complexity in terms of the number of vertices in the graph. We implemented the proposed algorithm and evaluated its performance with RDF databases and synthetic graphs to confirm its efficiency.

Denna studie bygger på hypotesen att det finns en risk för att läsning av lättläst nyhetsrapportering kan leda till en förenklad bild av verkligheten. Syftet är att ta reda på vad som händer i nyhetsrapportering med nyanser i en komplex fråga vid en lättläst-anpassning. Den rapportering som analyseras rör debatten om huruvida munskydd bör bäras av den svenska allmänheten som en strategi mot coronaviruset eller inte. Studien jämför den lättläst-anpassade tidningen 8 Sidor med den ordinarie dagstidningen Dagens Nyheter. Inledningsvis undersöks de övergripande skillnader i alla artiklar som skrivits på ämnet under tre månader, och därefter sker en jämförelse av 6 artiklar från varje tidning som bildar artikelpar med motsvarande innehåll. För detta ändamål används en strukturell textanalys inriktad på innehållsliga aspekter där teman som aktörer, hållningar och skäl fokuseras. Skillnaderna analyseras sedan utifrån hur de påverkar bilden av munskyddsfrågan i stort. Resultatet visar att 8 Sidor främst lyfter beslutsfattarnas perspektiv, förmedlar innehållet mer sakligt och objektivt inriktad på information om förändringar i beslut snarare än de olika åsikter som finns representerade i debatten. Tidningen ger en mer bestämd och definitiv bild av frågan än Dagens Nyheter som har större fokus på debatten. DN ger mer info om aktörernas hållningar och skäl, lyfter kritikerna mer, redovisar fler aktörer, fler målande lägesbeskrivningar och citat som ger en större förståelse för argumenten från båda sidor. Här lyfts uttalanden som innehåller garderingar om när, var, hur munskydd bör eller inte bör användas och modererande formuleringar som kanske och inte säkert. Innehållet framstår i stort som mer nyanserat och med en lägre grad av bestämdhet i DN. Resultatet bekräftar risken som tidigare forskning lyfter nämligen att nyanser faller bort vid lättläst-anpassning och att anpassningen ger en förenklad och mer konkret bild av läget. Studien styrker behovet av medvetenhet kring bortfall av innehåll och nyanser i lättläst-anpassningar för så väl utförare och mottagare av sådana anpassningar som lärare som vill använda de anpassade versionerna i sin undervisning.

Unwanted pregnancies and sexually transmitted infections (STIs) are major health concerns of women worldwide. These concerns have prompted efforts to develop Multipurpose Prevention Technologies (MPTs), which simultaneously provide contraception and prevent STIs, including HIV. LL-37, the only human cathelicidin and an effective spermicide on human sperm, has broad antimicrobial activity including in vitro activity against HIV. 17BIPHE2 is a truncated LL-37 peptide, engineered to contain 5 unnatural residues, thus limiting its protease degradation within vaginal fluid. Hence, this antimicrobial peptide (AMP) represents a promising MPT agent. It was therefore hypothesized that these peptides would be inhibitors of HIV infection in cell lines, PBMC, and CD4+ T cells. In the chronically infected ACH-2 cell line, there was significant reduction in p24 production when cells were treated with 17BIPHE2, but not LL-37. When 17BIPHE2 was pre-incubated with HIV prior to infection and present during infection, viral replication decreased in the TZM-bl reporter cell line, but this result was not recapitulated in the primary activated cells, PBMCs nor isolated CD4+ T cells. Conversely, pre-incubation of 17BIPHE2 with target cells prior to infection significantly inhibited HIV infection in a dose-dependent manner. Therefore, 17BIPHE2 may act on the cell or on the virus/cell interaction rather than on the virus itself to inhibit HIV infection.

No description available.

This thesis provides a summary of knowledge of grammar systems. The thesis proposes modifications of parallel oriented grammar systems to be usable in sequential parsing. Concept of grammar systems is extended to level of entire parsers, that are grouped into parsing system. Then the properties of these systems are examined. The aim of thesis is to introduce approaches to syntactic analysis based on grammar systems. Thesis is based on context-free methods of syntactic analysis, extending them and connecting them together. Great attention is dedicated to increase generative capacity of LL and LR parsing. There were created context-free structures within this thesis, which are capable to generate context-sensitive languages. This work also provides a simple recipe for implementation of these structures. We introduced generic concept of parsing, that enlarge generative power of conventional parsing methods. Using presented techniques it is possible to extend many of often used languages with context-sensitive elements, especially elements contradicting with pumping lemma.

Antimicrobial peptides (AMPs) are small proteins produced by epithelial surfaces, which have broad-spectrum antimicrobial and immunomodulatory activities. In the lung, skin and alimentary tract AMPs are known to be important in infectious and inflammatory conditions. Far less is known regarding the role of AMPs within the female reproductive tract, but as infection and inflammation are causes of preterm labour, AMPs may have a key function in maintain and protecting pregnancy. The major groups of human AMPs include the human beta defensins (HBDs), two antileukoproteinases (secretory leukocyte protease inhibitor (SLPI) and Trappin-2/Elafin), and the human cathelicidin hCAP18/LL-37, with several studies identifying their presence at sites throughout the reproductive tract. The cervix in pregnancy is positioned between the upper genital tract containing the developing fetus and the lower tract where infections usually arise. I hypothesise that AMPs are fundamental to mucosal immune defence of the cervix in pregnancy, preventing ascending infection and excessive inflammation that can cause preterm labour. This thesis focused on the human cathelicidin hCAP18/LL-37 and its role within the cervix and vagina. The aims of this thesis were to; investigate the inflammatory effects of LL-37 from cervical and vaginal derived epithelial cells and determine the pathways and receptors in which LL-37 may elicit its effects and how production may be regulated; investigate the role of CRAMP in a mouse model of preterm birth; and determine the production of AMPs by the pregnant cervix whilst investigating the relationship between AMP concentrations in cervicovaginal secretions and preterm labour. The inflammatory effect of LL-37 was investigated using cell lines derived from endocervical, ectocervical and vaginal epithelium. The study of these cell lines suggests divergent responses of cervical and vaginal epithelial cells. LL-37 mediated induction of IL-8 and IL-6 production from endocervical epithelial cells was observed in a dose-dependent and time-dependent manner, whilst ectocervical and vaginal cells also respond to treatment with LL-37 through IL-8 and IL-6 production. To determine a possible mechanism of action of LL-37 on IL-8 and IL-6 in the three cell lines, inhibitors against MAPK cascades, ERK, p38 MAPK and JNK, and known LL-37 receptors were investigated. In endocervical cells LL-37 mediated IL-8 occurs via activation of unidentified GPCRs, whilst in ectocervical cells this effect on IL‐8 and IL-6 is via the activation of ERK and p38 MAPK cascades. The mechanism by which LL-37 induces IL-8 secretion in vaginal epithelial cells remains unknown. Expression of LL-37 was shown to be mediated by vitamin D3 in vitro in cervical and vaginal epithelial cells. However when this relationship was investigated in vivo, using matched serum and cervicovaginal secretions from woman at early pregnancy, no correlation was observed between circulating vitamin D and cervicovaginal or circulating hCAP18/LL-37. However, the majority of women in this study reported with insufficient levels of vitamin D, which may effect the relationship observed with hCAP18/LL-37. Using a mouse model of LPS-induced preterm labour, to mimic the presence of intrauterine infection bacterial infection, I aimed to characterise the role of CRAMP, the mouse orthologue of hCAP18/LL-37, in the lower inflammatory and immune response that results in preterm labour. Wild type C57Bl/6J mice receiving an intrauterine injection of LPS deliver prematurely, within 24 hours of injection. However mice deficient in CRAMP (Camp -/-) receiving an intrauterine injection of LPS deliver significantly later and have a non-significant increase in pup survival compared to wild type C57Bl/6J mice. Cervical tissue collected post partum showed no difference in inflammatory markers between wild type C57Bl/6J and Camp -/- mice, however there was increased expression of the neutrophil chemoattractant marker, Cxcl5, and the neutrophil marker, Ngp in Camp -/- mice. In the lower genital tract, levels of antimicrobial peptides were determined in samples of cervicovaginal secretions collected from pregnant women. AMPs, hCAP18/LL-37, HBD-2 and SLPI were found in cervicovaginal secretions, and levels of hCAP18/LL-37 were increased in women with the common vaginal infection bacterial vaginosis. However no relationship was identified between the concentration of AMPs and preterm birth in this study. This work has shown that the lower genital tract, where infections that are associated with preterm labour originate, expresses the human cathelicidin hCAP18/LL-37. It may play an important role in modulating the immune response to invading infection associated with preterm labour. Further investigation of these responses may increase understanding of the physiology and pathophysiology of labour, and lead to strategies for the prevention of premature delivery.

Submitted by NOALA VICENSOTO MOREIRA MILHAN null (noalinha@gmail.com) on 2017-03-14T15:32:19Z No. of bitstreams: 1 TESE_FINAL_biblioteca_pdf_com ficha..pdf: 9569489 bytes, checksum: 1675ea8facc1f735605660b0b01b8cad (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-03-20T22:29:35Z (GMT) No. of bitstreams: 1 milhan_nvm_dr_sjc.pdf: 9569489 bytes, checksum: 1675ea8facc1f735605660b0b01b8cad (MD5) / Made available in DSpace on 2017-03-20T22:29:36Z (GMT). No. of bitstreams: 1 milhan_nvm_dr_sjc.pdf: 9569489 bytes, checksum: 1675ea8facc1f735605660b0b01b8cad (MD5) Previous issue date: 2017-01-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O peptídeo LL-37 (catelicidina derivada de humano), é liberado por algumas células humanas e capaz de neutralizar os tecidos com lipopolissacarídeo (LPS), além de atrair células da polpa, e induzir a angiogênese, características que o tornam um possível adjunto para a regeneração do complexo dentino-pulpar. O objetivo desse trabalho foi avaliar in vitro a biocompatibilidade do peptídeo LL-37 nas concentrações de 5 e 10 μg/mL, e sua possível atuação na diferenciação de células-tronco da polpa dentária (DPSC) para odontoblastos- like. Com esse propósito, foram avaliados: (a) a citotoxicidade, pelo teste MTT; (b) a genotoxicidade, através do ensaio do micronúcleo; (c) a produção e quantificação de óxido nítrico; (d) as fases do ciclo celular, por citometria; (e) a expressão de alguns genes associados à formação de tecido mineralizado, através do teste qRT-PCR; (f) o conteúdo de proteína total; (g) a atividade de fosfatase alcalina (ALP); e (h) a produção de sialofosfoproteína dentinária (DSPP), pelo ensaio imunoenzimático ELISA. Foi observado que as concentrações de 5 e 10 μg/mL de LL-37 não foram citotóxicas e ainda aumentaram, em geral, a viabilidade celular (p<0,05), sendo que os maiores valores de absorbância foram observados no 3° dia de contato. As concentrações testadas também não induziram genotoxicidade, após 7 dias de contato, tendo sido genotóxico apenas o grupo controle positivo (EMS) (p<0,05). Ainda, não foi observado diferença estatisticamente significativa na produção de nitrito, pelas células expostas ao LL-37 após 7 dias, em ambas as concentrações. A análise do ciclo celular, evidenciou maior porcentual de células na fase G0/G1, em todos os grupos (p<0,05). Quando estes foram comparados, foi observado maior quantidade de células na fase G0/G1 na concentração de 10 μg/mL de LL- 37 comparada ao grupo controle (p<0,05). Por outro lado, o grupo controle exibiu mais células na fase G2 e em mitose (M) que os grupos tratados com 5 e 10 μg/mL de LL-37 (p<0,05), e mais células na interfase (S) que o grupo tratado com 10 μg/mL de LL-37 (p<0,05). A análise da expressão gênica demonstrou que não houve aumento de expressão dos genes fosfatase alcalina, osteocalcina, osteopontina e Runx2 após tratamento com ambas as concentrações do peptídeo, no 3° dia. Além disso, não foi observado diferença estatisticamente significativa na ALP nos grupos tratados e controle, após 3 e 14 dias, enquanto o conteúdo de proteína total foi maior aos 14 dias nos grupos tratados com LL-37 (p<0,05). Ainda, aos 3 dias, a produção da proteína DSPP foi maior no grupo tratado com 10 μg/mL de LL-37 (p<0,05). Com base nesses resultados, pode-se concluir que o LL-37 é biocompatível nas concentrações testadas nesse trabalho, e ainda aumenta o número de células viáveis, principalmente em período inicial. Além disso, aos 3 dias, na concentração de 10 μg/mL, ele retarda o ciclo celular e aumenta a expressão da proteína DSPP, além de aumentar a síntese proteica aos 14 dias, o que indica que esse peptídeo pode desempenhar algum tipo de função na diferenciação odontoblástica. / The LL-37 peptide (human derived cathelicidin) is released by some human cells and able of neutralizing the tissues that present lipopolysaccharide (LPS), as well as, attracts pulp cells and induces angiogenesis; characteristics that makes it a possible adjunct for regeneration of the dentin-pulp complex. The aim of this study was evaluate in vitro the biocompatibility of LL-37 in the concentrations of 5 and 10 μg/mL, and its possible performance in the differentiation of dental pulp stem cells (DPSC) into odontoblasts-like cells. For this purpose, it was evaluated: (a) the cytotoxicity by MTT assay; (b) the genotoxicity by the micronucleus test; (c) the production and quantification of nitric oxide; (d) the cell cycle, by flow cytometry; (e) the expression of genes associated with the mineralization by qRT-PCR; (f) the total protein content; (g) the alkaline phosphatase activity (ALP); and (h) the production of dentine sialofosfoprotein (DSPP) by indirect enzyme-linked immunosorbent assay (ELISA). It was observed that the concentrations of 5 and 10 μg/ml of LL-37 were not cytotoxic, in addition to they increased, in general, the cell viability (p<0,05). Moreover, higher absorbance values were observed on 3rd day of contact. After 7 days, the tested concentrations also did not induce genotoxicity, (p<0,05); only the positive control group (EMS) was genotoxic (p<0.05). Furthermore, there was not statistical significance in the nitrite production by the cells exposed to LL-37 for 7 days, in both concentrations. The cell cycle test showed higher percentage of cells in the phase G0/G1 in all groups (p<0.05). When they were compared, it was noticied that concentration of 10 ug/ml of LL-37 arrested the cells in G0/G1 compared to the control group (p<0.05). On the other hand, the control group, exhibited higher amount of cells in G2 and mitosis (M) than the others (p<0.05) and also higher number of cells in interfase (S) than the group treated with 10 μg/mL of LL-37 (p<0.05). On the 3rd day, the analysis of gene expression demonstrated no increase in the expression of the genes alkaline phosphatase, osteocalcin, osteopontin and Runx2, after treatment with both peptide concentrations. Furthermore, it was not observed statistical significance in the ALP in the treated and control groups after 3 and 14 days, while total protein content was higher in the groups treated with LL-37, at 14 days (p<0.05). On the 3rd day, the production of DSPP protein was higher in the group treated with 10 μg/mL of LL-37 (p<0.05). Based on these results, it can be concluded that LL-37 is biocompatible at these concentrations and increases the number of viable cells, especially in the initial period. Moreover, on the 3rd day, the concentration of 10 μg/mL arrests the cell cycle, and increases the expression of DSPP protein, in addition to raising the protein content at 14 days, which indicates that this peptide may present some kind of function in the odontoblastic differentiation.