Many students in South Africa are unable to cope with the academic demands of tertiary education as they are not fully prepared for Higher Education (HE). Various inefficiencies in the South African HE system have been identified, including low throughput rates, student dissatisfaction, unsatisfying graduation rates, learner dropouts, learner repetition, motivation, self–efficacy, attitude, personality differences, maturation, the retention of failing learners and unit costs. Student performance and satisfaction cause concern for the government and the HE sector. The purpose of this study is to understand student satisfaction amongst Open Distance Learning BEd Hons students. It further aims to improve student satisfaction and quality in the programme by recognising the context sensitive needs, expectations and experiences of students from different cultural–language groups, as well as constructing guidelines to improve satisfaction. The purposeful sampling consisted of Second year BEd Hons teacherstudents enrolled for open distance learning at the School for continuing teacher education (SCTE). A total of 34 students participated in the study. This number comprised of fifteen students from the focus–group interviews and nineteen students who completed open–ended questionnaires. Students were chosen according to three criteria dimensions: major language groups, gender and number of years teaching experience. This study followed a qualitative investigation of two semi–structured, open–ended focus–group interviews in the format of conversations, as well as documentary analysis of the teaching and learning policy of the North West University (NWU), and an open–ended questionnaire. The data were taperecorded for accurate transcription and analysed by using Atlas.ti. Through the use of Atlas.ti, I constructed categories of recurring patterns in the dataset, and explored the relationships of these categories. Different strategies were used to enhance validity and reliability respectively. The findings indicated that students’ satisfaction with HE environment is influenced by the quality of the programmes offered to them, communication between lecturers/facilitators and students, environment at the learning centres and the support that students received from HEI. The students in their capacity as clients with Higher education institutions (HEIs) are influenced by the support they receive from their work environment, as well as the level of appreciation they receive from HEI regarding their own culture and values. They also value iii the environment they experience during course facilitations at the HEIs. The various student attributes also play a significant part in their satisfaction levels towards the HEIs. Findings also highlighted that students were not satisfied with the support they received from the Open distance learning (ODL) unit. It is clear that the students’ perception of the quality of the programme influences their level of satisfaction. Students are mostly satisfied with the quality of the programme but they feel the communication as well the support from HEI and ODL is not adequate. The students indicated that HEI and ODL do not display sufficient understanding and concern for students. They feel there should be a greater commitment from HEI and ODL to understand and consider the profiles of the students. HEI and ODL should actively consider the background, culture, values, attributes, and personal, as well as domestic circumstances of their students. The BEd Hons programme is a valuable and popular programme, but the responsibility rests with both HEI and ODL to ensure that both the quality and delivery of this programme are enhanced and improved so as to guarantee higher levels of satisfaction amongst students. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2012.

Many students in South Africa are unable to cope with the academic demands of tertiary education as they are not fully prepared for Higher Education (HE). Various inefficiencies in the South African HE system have been identified, including low throughput rates, student dissatisfaction, unsatisfying graduation rates, learner dropouts, learner repetition, motivation, self–efficacy, attitude, personality differences, maturation, the retention of failing learners and unit costs. Student performance and satisfaction cause concern for the government and the HE sector. The purpose of this study is to understand student satisfaction amongst Open Distance Learning BEd Hons students. It further aims to improve student satisfaction and quality in the programme by recognising the context sensitive needs, expectations and experiences of students from different cultural–language groups, as well as constructing guidelines to improve satisfaction. The purposeful sampling consisted of Second year BEd Hons teacherstudents enrolled for open distance learning at the School for continuing teacher education (SCTE). A total of 34 students participated in the study. This number comprised of fifteen students from the focus–group interviews and nineteen students who completed open–ended questionnaires. Students were chosen according to three criteria dimensions: major language groups, gender and number of years teaching experience. This study followed a qualitative investigation of two semi–structured, open–ended focus–group interviews in the format of conversations, as well as documentary analysis of the teaching and learning policy of the North West University (NWU), and an open–ended questionnaire. The data were taperecorded for accurate transcription and analysed by using Atlas.ti. Through the use of Atlas.ti, I constructed categories of recurring patterns in the dataset, and explored the relationships of these categories. Different strategies were used to enhance validity and reliability respectively. The findings indicated that students’ satisfaction with HE environment is influenced by the quality of the programmes offered to them, communication between lecturers/facilitators and students, environment at the learning centres and the support that students received from HEI. The students in their capacity as clients with Higher education institutions (HEIs) are influenced by the support they receive from their work environment, as well as the level of appreciation they receive from HEI regarding their own culture and values. They also value iii the environment they experience during course facilitations at the HEIs. The various student attributes also play a significant part in their satisfaction levels towards the HEIs. Findings also highlighted that students were not satisfied with the support they received from the Open distance learning (ODL) unit. It is clear that the students’ perception of the quality of the programme influences their level of satisfaction. Students are mostly satisfied with the quality of the programme but they feel the communication as well the support from HEI and ODL is not adequate. The students indicated that HEI and ODL do not display sufficient understanding and concern for students. They feel there should be a greater commitment from HEI and ODL to understand and consider the profiles of the students. HEI and ODL should actively consider the background, culture, values, attributes, and personal, as well as domestic circumstances of their students. The BEd Hons programme is a valuable and popular programme, but the responsibility rests with both HEI and ODL to ensure that both the quality and delivery of this programme are enhanced and improved so as to guarantee higher levels of satisfaction amongst students. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2012.

Made available in DSpace on 2014-12-17T14:07:22Z (GMT). No. of bitstreams: 1 AntonioCPS.pdf: 2085220 bytes, checksum: 8e64ae2c2f5ffe8a64dd3420c9c87327 (MD5) Previous issue date: 2007-03-23 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / In this work was used a plasma torch of non transferred arc with argon as work gas, using a power supply with maximum DC current of 250 A and voltage of 30 V to activate the plasma and keep it switched on. The flame temperature was characterized by optical emission spectroscopy, through Boltzmann-plot-method. The torch has been used like igniter in the aluminothermic reduction of the mixture tantalum oxide and aluminum, seeking to obtain metallic tantalum. In heating of the reagents only one particle will be considered to study interactions between plasma-particle, seeking to determinate its fusion and residence time. The early powders were characterized by laser granulometry, scanning electron microscopy (SEM) and X-ray diffraction analysis. The final product of this reaction was characterized by SEM and X-ray diffraction. Crystallite size was calculated by the Scherrer equation and microdeformation was determined using Willamsom-Hall graph. With Rietveld method was possible to quantify the percentile in weight of the products obtained in the aluminothermic reaction. Semi-quantitative chemical analysis (EDS) confirmed the presence of metallic tantalum and Al2O3 as products of the reduction. As was waited the particle size of the metallic tantalum produced, presents values in nanometric scale due the short cooling time of those particles during the process / Neste trabalho foi utilizada uma tocha de plasma de arco n?o transferido com arg?nio como g?s de trabalho, utilizando uma fonte de pot?ncia com corrente m?xima de 250 A e tens?o m?xima de sa?da de 30 V fornecida pelo fabricante. A temperatura da tocha foi caracterizada atrav?s da espectroscopia de emiss?o ?ptica, utilizando a curva de Boltzmann. A tocha foi usada como ignitor para a rea??o de redu??o aluminot?rmica do ?xido de t?ntalo mais alum?nio para a produ??o de t?ntalo met?lico. No aquecimento dos reagentes apenas uma part?cula ser? considerada para o estudo da intera??o tocha-part?cula, com o objetivo de determinar seu tempo de fus?o e resid?ncia. Os p?s de partida foram caracterizados atrav?s da granulometria a laser, microscopa eletr?nica de varredura (MEV) e difra??o de raios X. O produto final desta rea??o foi caracterizado por MEV e difra??o de raios X. O tamanho de cristalito foi calculado atrav?s da equa??o de Scherrer e a microdeforma??o foi determinada utilizando o gr?fico de Willamsom-Hall. Com o m?todo de Rietveld foi poss?vel quantificar o percentual em peso do produto da rea??o aluminot?rmica. An?lise qu?mica semiquantitativa (EDS) confirmou a presen?a do Ta met?lico e Al2O3 como produtos da redu??o. Como era de se esperar, o tamanho das part?culas do t?ntalo met?lico produzida apresenta valores na faixa de nan?metro devido pequeno tempo de resfriamento durante o processo

Text in Afrikaans / Die doel van die studie is om die leefwereld van die aggressiewe adolessente seun te verken. Aggressie word beskou as 'n gedragsafwyking wat op fisieke, verbale of passiewe wyses kan manifesteer. Die oorsake van aggressiewe gedragsmanifestasies by die adolessente seun word hoofsaaklik gevind in die ontoereikende gesinsrelasies. Gevoelens van ongeborgenheid, verwardheid en verwerping is dan die gevolg. 'n Onrealisties positiewe of -negatiewe selfkonsep kan hieruit voortvloei en kan daartoe lei dat die aggressiewe adolessente seun betrokke raak by negatiewe portuurrelasies, waar onder andere rook, dwelm- en drankmisbruik asook roekelose gedrag manifesteer. Ult hierdie literatuurbevindinge is twaalf postulate gestel en bespreek. Vyf idiografiese studies is onderneem, waarvan drie volledig bespreek is. Die bevindings uit hierdie studies sluit aan by die feite wat ult die literatuurstudie oor die leefwereld van die aggressiewe adolessente seun verkry is. Vroee uitkenning, ouerleiding en navorsing met betrekking tot hulpprogramme aan terapeute word aanbeveel om aggressiewe gedragsmanlfestasles by die adolessente seun te voorkom / The purpose of this study is to explore the lifeworld of the aggressive adolescent boy. Aggression is regarded as deviant behaviour, that may manifest itself physically, verbally or passively. The causes of aggressive behaviour in the adolescent boy can be due to inadequate family relationships. Feelings of insecurity, confusion and rejection are the results of the problematic relationships. An unrealistic positive or negative self concept may develop that might lead to involvement with the negative peer group. Smoking, alcohol and drug abuse, as well as reckless behaviour may occur. Twelve postulates have been determined and discussed. Five idiographic studies have been done. Three are discussed in detail. Deductions made from these studies are in agreement with findings in existing literature of the life world of the adolescent boy. Early identification parental guidance and research regarding therapeutical programmes are recommended to prevent aggressive behaviour with the adolescent / Psychology of Education / M. Ed. (Spesialisering in Voorligting)

Les aciers bainitiques sont utilisés industriellement pour leur bon compromis entre résistance, ductilité et ténacité. Cependant, après obtention de sa microstructure d'emploi, l’acier peut subir des maintiens additionnels en température (soit en fin de fabrication et/ou lors de son utilisation), susceptibles de dégrader ses propriétés. Ces travaux de thèse cherchent à comprendre les origines microstructurales de cette dégradation. Pour ce faire, des traitements thermiques contrôlés ont été appliqués à des aciers de nuances modèles FeNiC et FeNiMnC. Une première série de traitements a permis de fabriquer des microstructures bainitiques supérieure, inférieure, martensitique et mixtes. Ces produits de transformation bruts ont été caractérisés et analysés en détail, en particulier par EBSD en résolution angulaire améliorée. Les données ont été exploitées pour reconstruire les ex-grains austénitiques et distinguer les différents produits de transformation par l'organisation spatiale de leurs variants cristallographiques. Une deuxième série de traitements a consisté à soumettre ces microstructures à des maintiens isothermes prolongés. Nous avons montré que ces microstructures bainitiques en lattes ne sont pas stables dans certaines conditions ultérieures de maintien isotherme. Dans les cas les plus sévères, nous avons observé un processus de « granularisation » de la microstructure en lattes avec disparition des variants fortement désorientés et une maturation des carbures. Ces phénomènes sont observés sur nos alliages modèles y compris sur des temps courts (<1h) à basses températures (300°C). Ces évolutions ainsi que leurs cinétiques ont été investiguées à différentes échelles en couplant des observations en MEB, EBSD, MET et aussi in situ par DRX Haute Energie sur grands instruments. La composition chimique et la microstructure initiale affectent sensiblement les cinétiques. Mais nous avons surtout pointé le rôle majeur de la présence (même résiduelle) de bainite dite supérieure dans la microstructure initiale pour amorcer le processus de granularisation, indépendamment de la température de dénaturation. L’ensemble des résultats permet de discuter les possibles mécanismes sous-jacents et leurs forces motrices et ouvre une discussion plus large sur la classification des bainites / Bainitic steels are widely used in industry thanks to their good combinations of strength, toughness and ductility. Meanwhile, after obtaining the targeted microstructure, the steel can undergo additional isothermal holdings (either during manufacturing and/or during usage) prone to degrade its properties. The thesis work aims at understanding the microstructural origins of this degradation. To achieve this, we applied controlled heat treatments on model FeNiC and FeNiMnC steel grades. A first set of heat treatments allowed us to obtain different microstructures; upper and lower bainites, martensite and mixed concepts. These transformation products were characterized and analyzed in detail, particularly by EBSD with improved angular resolution. Data was operated to reconstruct prior austenitic grains and to distinguish the different transformation products according to their crystallographic variant spatial organization. A second set of heat treatments consisted in aging these microstructures by extended isothermal holdings. We show that lath-like bainitic microstructures are not stable under certain isothermal conditions. In the most advanced cases, we observed a « granularization » process of the lath microstructure, associated with high misoriented variant disappearance and carbides ripening. These phenomena were observed for the studied model alloys, even within short holding times (<1h) and at low temperatures (300°C). These highlighted evolutions as well as their kinetics were investigated at different scales, coupling SEM observations, EBSD, TEM and in situ XRD High Energy on large instruments. The initial microstructure and the steel chemical composition affect significantly the « granularization » kinetics. But we have above all put the light on the major role of the presence of an upper bainite fraction (even a residual one) in the initial microstructure, to start the granularization phenomenon, independently of aging temperature. All of these results allow discussing possible mechanisms with their respective driving forces and opening larger discussion about bainite classification

Made available in DSpace on 2014-12-17T15:32:25Z (GMT). No. of bitstreams: 1 AndreaFS_tese.pdf: 610478 bytes, checksum: 22934e3fba7a401686d3b0057e0e7f35 (MD5) Previous issue date: 2007-07-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The expression of bone morphogenetic proteins (BMPs) is altered in a variety of human canceres. The BMP-2/4 and BMPR-IA were recently shown to be overexpressed in high-risk premalignant and malignant lesions of oral epithelium. The present study analysed the expression of BMP-2/4 and BMPR-IA in Oral Squamous Cell Carcinoma (OSCC) such as their implications in disease prognostic using munohistochemistry. Ten cases of Oral Fibroepithelial Hiperplasia were selected as a control group. The experimental group included 16 cases of OSCC without metastases and 7 cases of OSCC metastatic. The presence or absence of nodal metastases was used as parameter to evaluated the disease prognostic. The results demonstrated weak immunoreactivity for BMP-2/4 and BMPR-IA in every case of the control group. In the cases of OSCC with metastases an overexpression of BMP-2/4 (71,4%) was observed while the BMPR-IA showed weak expression (85,7%). In the cases of OSCC without metastases BMP-2/4 (62,5%) and BMPR-IA showed strong immunostaining standing out an overexpression of the receptor in all the specimens. Observed statistical significance for correlation between the oral cancer prognostic and the staining intensity of the BMP-2/4 (p=0,002). There wasn t statistical significance for association between the staining intensity of the BMPR-IA and the disease prognostic (p<0,001). In conclusion, this findings suggest that the overexpression of BMP-2/4 associated with the loss of expression of the BMPR-IA in OSCC metastatic has prognostic relevance, as the loss of sensitivity to BMPs can be an indicative of metastases development in OSCC / A express?o das prote?nas morfogen?ticas ?sseas (BMPs) est? alterada em v?rios c?nceres humanos. A BMP-2/4 e o BMPR-IA foram recentemente encontrados superexpressos em les?es malignas e pr?-malignas de alto risco em epit?lio oral. Este estudo analisou a express?o da BMP-2/4 e seu receptor BMPR-IA em 23 esp?cimes de Carcinoma Epiderm?ide Oral (CEO), utilizando a imuno-histoqu?mica. O grupo controle constou de 10 casos de Hiperplasia Fibro-epitelial da mucosa oral. O grupo experimental foi constitu?do por 16 casos de CEO n?o metast?tico e 7 casos de CEO metast?tico. Utilizou-se o par?metro presen?a ou aus?ncia de met?stase nodal para avaliar o progn?stico da doen?a. Os resultados demonstraram imunorreatividade fraca para a BMP-2/4 e o BMPR-IA em todos os esp?cimes do grupo controle. No grupo experimental com met?stase, a BMP-2/4 exibiu forte expressividade (71,4%), enquanto que o BMPR-IA mostrou fraca express?o (85,7%). No grupo experimental sem met?stase, evidenciou-se forte express?o para a BMP-2/4 (62,5%) e para o BMPR-IA (100%). Encontrou-se signific?ncia estat?stica para a associa??o entre o progn?stico do CEO e a intensidade de marca??o da BMP-2/4 (p=0,002). Para o BMPR-IA n?o houve signific?ncia estat?stica ? sua associa??o com o progn?stico da doen?a (p<0,001), em fun??o do tamanho da amostra. Portanto, os resultados sugerem que a fraca expressividade do BMPR-IA associada ? forte express?o da BMP-2/4, no grupo experimental com met?stase, tem relev?ncia progn?stica, j? que a perda de sensibilidade ?s BMPs, atrav?s da perda de express?o de seus receptores pode ser indicativo de desenvolvimento de met?stase em CEO

Made available in DSpace on 2014-12-17T15:32:28Z (GMT). No. of bitstreams: 1 Tese_GeorgeJFN.pdf: 2720479 bytes, checksum: 6d72db8b12a0e5f743d69a67430d66b7 (MD5) Previous issue date: 2010-02-18 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue / As metaloproteinases da matriz extracelular-7 (MMP-7) e -9 (MMP-9) modulam importantes fun??es relacionadas ao desenvolvimento, invas?o e met?stase de diversos c?nceres humanos, dentre os quais o carcinoma epiderm?ide de l?ngua (CEL). Entretanto, fatores gen?ticos individuais, tais como polimorfismos de nucleot?deo ?nico (SNPs) funcionais, influenciam no padr?o de express?o proteica dessas MMPs, podendo estar relacionados ? variabilidade no comportamento cl?nico tumoral observado em pacientes com CEL. Neste contexto, o presente trabalho objetivou, atrav?s de an?lise em sec??o transversal, estudar a associa??o entre a frequ?ncia dos SNPs funcionais MMP-7 -181 A/G e MMP-9 -1562 C/T e as caracter?sticas cl?nicas (idade, sexo e met?stase) e patol?gicas (grada??o histol?gica e express?o imuno-histoqu?mica) em uma s?rie de casos de CEL. A genotipagem dos referidos SNPs foi executada por PCR-RFLP em amostras de DNA de 71 casos de CEL e de 60 indiv?duos sem c?ncer, que constitu?ram o grupo controle. Dentre os resultados da presente pesquisa, evidenciou-se que a frequ?ncia dos alelos polim?rficos MMP-7 -181 G e MMP-9 -1562 T nos pacientes com CEL foi de 28% e 12%, respectivamente, sendo as frequ?ncias dos heterozigotos A/G (RP = 2.00; p < 0.001) e C/T (RP = 1.54; p = 0.014) significativamente maiores neste grupo de pacientes que no grupo controle. A preval?ncia dos pacientes portadores da combina??o dos SNPs estudados associou-se significativamente aos casos de CEL (RP = 2.00; p = 0.011) e ? met?stase (RP = 2.00; p < 0.001). Ademais, junto ? frequ?ncia dos SNPs analisados, a idade, sexo, grada??o histol?gica e imunoexpress?o da MMP-7 e -9 constitu?ram par?metros clinicopatol?gicos relevantes para a identifica??o de subgrupos populacionais mais predispostos ao desenvolvimento do CEL e met?stase. Frente a estes resultados, sugere-se que os n?veis de express?o da MMP-7 e -9 influenciam consideravelmente no balan?o entre suas fun??es pr? e antineopl?sicas e, consequentemente, no perfil clinicopatol?gico do carcinoma epiderm?ide de l?ngua.

Made available in DSpace on 2014-12-17T15:32:33Z (GMT). No. of bitstreams: 1 CyntiaHPC_TESE.pdf: 1535929 bytes, checksum: 7d7c8298def3233365b9ad5eb617d015 (MD5) Previous issue date: 2014-02-27 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the oral cavity and reach a large number of individuals, has become an important public health problem. Studies have demonstrated changes in pathway components BMP in various types of cancers as prostate, colon, breast, gastric and OSCCs. Is the current knowledge that these proteins may exert pro-tumor effect in more advanced stages of neoplastic development coming to favor progression and invasion tumor. The inhibition of the signaling pathway BMP-2 through its antagonists, have shown positive results of antitumor activity and use of Noggin may be a novel therapeutic target for cancer. Given this evidence and the few studies with BMP-2, Noggin and OSCC, the objective of this research was to evaluate the effect of BMP-2 and its antagonist Noggin on proliferation and migration cell in line of cell cultures of human tongue squamous cell carcinoma (SCC25). The study was divided in three groups, a control group, where SCC25 cells suffered no treatment, a BMP-2 group, in which cells were treated with 100ng/ml of BMP-2 and a group of cells that were treated with 100ng/ml of Noggin. For the proliferation assay and cell cycle were established three time intervals (24, 48 and 72 hours). Proliferative activity was investigated by trypan blue and cell cycle analysis by staining with propidium iodide flow cytometry. The potential for migration / invasion of SCC25 cells was performing by a cell invasion assay using Matrigel in a 48-hour interval. The proliferation curve showed a higher proliferation in cells treated with BMP-2 in 72 hours (p < 0.05), and lower overgrowth and cell viability in Noggin group. Recombinant proteins favored a greater percentage of cells in cell cycle phase Go/G1 with a statistically significant difference in the interval of 24 hours (p < 0.05). BMP- 2 produced a greater invasion of cells studied as well as its antagonist Noggin inhibits invasion of cells (p < 0.05). Thus, these results indicate that BMP-2 promotes malignant phenotype, dues stimulates proliferation and invasion of SCC25 cells and, its antagonist Noggin may be an alternative treatment, due to inhibit the tumor progression / O carcinoma epiderm?ide oral (CEO) representa a neoplasia maligna mais prevalente na cavidade oral e por atingir um grande n?mero de indiv?duos, acaba se tornado um relevante problema de sa?de p?blica. Muitos estudos demonstram altera??es nos componentes da via BMP em v?rios tipos de tumores, como os de pr?stata, c?lon, mama, g?stricos e CEOs. ? do conhecimento atual que essas prote?nas podem exercer efeito pr?-tumoral em est?gios mais avan?ados do desenvolvimento neopl?sico vindo a favorecer a progress?o e invas?o tumoral. A inibi??o da via de sinaliza??o da BMP-2, atrav?s dos seus antagonistas, tem mostrado resultados positivos de a??o antitumoral e que assim, o uso do Noggin pode ser um novo alvo terap?utico contra o c?ncer. Diante destas evid?ncias e dos escassos trabalhos com BMP-2, Noggin e CEO, o objetivo desta pesquisa foi avaliar o efeito da BMP-2 e seu antagonista Noggin sobre a prolifera??o e migra??o celulares em culturas de c?lulas de carcinoma epiderm?ide de l?ngua humana (SCC25). Foi feita a divis?o em tr?s grupos de estudo, um grupo controle, onde as c?lulas SCC25 n?o sofriam tratamento com subst?ncia alguma, um grupo BMP-2, no qual as c?lulas eram tratadas com 100ng/ml de BMP-2 e um grupo de c?lulas que eram tratadas com 100ng/ml de Noggin. Para o ensaio de prolifera??o e ciclo celular foram estabelecidos tr?s intervalos de tempo (24, 48 e 72 horas). A atividade proliferativa foi investigada por azul de tripan e a an?lise do ciclo celular atrav?s da marca??o por iodeto de prop?dio em Citometria de fluxo. O potencial de migra??o/invas?o das c?lulas SCC25 foi avaliado atrav?s da realiza??o de um ensaio de invas?o celular utilizando o matrigel em um intervalo de 48 horas. A curva de prolifera??o revelou maior crescimento celular nas c?lulas tratadas com BMP-2 no intervalo de 72 horas (p<0.05) e menor crecimento e viabilidade celular no grupo Noggin. As prote?nas recombinantes favoreceram a maior porcentagem das c?lulas na fase do ciclo celular Go/G1 com diferen?a estatisticamente significativa no intervalo de 24 horas (p<0,05). A BMP-2 promoveu uma maior invas?o das c?lulas estudadas, assim como o seu antagonista Noggin inibiu a invas?o das c?lulas estudadas (p<0,05). Dessa forma, os resultados indicam que a BMP-2 favorece o fen?tipo maligno, pois estimula a prolifera??o e invas?o das c?lulas SCC25 e seu antagonista Noggin pode ser uma alternativa terap?utica pois inibiu essas caracter?sticas pr?-tumorais

Made available in DSpace on 2014-12-17T15:32:34Z (GMT). No. of bitstreams: 1 ErickaJDS_tese.pdf: 814077 bytes, checksum: c31b79040c7db1898443078febad2a0d (MD5) Previous issue date: 2007-03-09 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The progression of the oral squamous cells carcinomas (OSCCs) seems to suffer influence from related factors to the host, as local and systemic immunologic response, which are essential to the antineoplasic defenses. The purpose of this study was evaluate the local immunity in 30 tongue and 20 lower lip SCC by immunohistochemistry method, utilizing antibodies anti-CD3, CD4, -CD8, -CD25 e -&#950;(zeta), which immunoexpressions were compared considering the anatomical localization, the intensity of the inflammatory infiltrate into the front of invasion and metastases. The CD4/CD8+ ratio was calculated for each case and associate with the mentioned variable, being the intensity of the inflammatory infiltrated also compared with the anatomical localization and metastase and for this the cases had been grouped in two categories: (n = 10) absent/scarce inflammatory infiltrate; and (n = 40) moderate/intense infiltrate. Fisher?s exact test was performed (&#945;= 0.05) and it was not observed any significant correlation between these groups with anatomical sites and metastases. With regard to the immunoexpression, the CD3+, CD4+, CD8+ and CD25+ cells count was higher in the lower lip SCCs while the anti-&#950;immunomarcation was more evident in the non metastatic cases. Through the statistical analyses, it was verified that the CD3 exhibited positive-significant correlation with the inflammatory infiltrate (p = 0.023). Furthermore, antibodies against CD8 and CD25 cells were also significantly correlated with the inflammatory infiltrate (p = 0.002 and 0.030, respectively) and with the anatomical site (p = 0.004 and p = 0.004) mainly in the lower lip SCCs. CD4/CD8 ratio did not show significant association with metastase nor with anatomical localization. We conclude that the inflammatory infiltrated of the Bryne s (1998) system did not constitute an indicator of aggressiveness in the tongue and lower lip SCCs analyzed and that clinical behavior of the SCCs studied was related in part to the immunohistochemical profile of infiltrated the inflammatory present in tumoral invasion front / A progress?o dos carcinomas epiderm?ides orais (CEOs) parece sofrer influ?ncia de fatores relacionados ao hospedeiro, como a resposta imunol?gica local e sist?mica, as quais parecem ser essenciais para a defesa anti-neopl?sica. O presente estudo teve por objetivo analisar a imunidade local em 30 casos de CEs de l?ngua e 20 de l?bio inferior, atrav?s do m?todo da imuno-histoqu?mica, utilizando os anticorpos anti-CD3, -CD4, -CD8, -CD25 e -&#950;(zeta), comparando a imunomarca??o em ambas as localiza??es, com a intensidade de infiltrado inflamat?rio no front de invas?o e com presen?a ou n?o de met?stase. A raz?o de c?lulas CD4/CD8+ foi calculada para cada caso e associada com as vari?veis mencionadas, sendo a intensidade do infiltrado inflamat?rio comparada tamb?m com a localiza??o anat?mica e met?stase e para isso os casos foram agrupados em duas categorias (infiltrado escasso ou ausente E/A e infiltrado intenso ou moderado I/M), sendo encontrado 10 casos na categoria E/A e 40 na categoria I/M. Aplicado o teste exato de Fisher n?o verificamos associa??o significativa destes grupos com o s?tio anat?mico ou com met?stase. Em rela??o ? imunomarca??o, a contagem das c?lulas CD3+, CD4+, CD8+ e CD25+ foi maior nos CEs de l?bio inferior e sem met?stase, enquanto que o anti-&#950;foi mais expresso apenas nos casos sem met?stase. Atrav?s da an?lise estat?stica verificou-se que os anticorpos anti-CD3, anti-CD8 e anti-CD25 exibiram associa??o significativa positiva com o infiltrado inflamat?rio (p=0.023, p=0.002 e p=0.030, respectivamente); e os anticorpos anti-CD8 a anti-CD25 estiveram associados de forma positiva com a localiza??o anat?mica, ambos com valores de p=0.004, estando estes mais presentes nos CEs de l?bio inferior. A raz?o CD4/CD8 n?o exibiu associa??o significativa com met?stase nem com localiza??o anat?mica. Conclu?mos que o padr?o infiltrado inflamat?rio da grada??o histol?gica de malignidade de Bryne (1998) n?o constituiu um indicador de agressividade nos CEs de l?ngua e l?bio inferior analisados, e que o comportamento cl?nico dos CEs estudados esteve relacionado em parte ao perfil imuno-histoqu?mico do infiltrado inflamat?rio presente no front de invas?o tumoral

Le travail retranscrit dans cette thèse regroupe l'étude de différents processus biologiques impliqués dans la synthèse protéique bactérienne. Dans un premier chapitre, les origines de la synthèse protéique au temps du monde ARN sont traitées en guise d'introduction. Ce travail théorique se poursuit par la présentation d'une structure à haute résolution du facteur d'élongation G (EF-G) en complexe avec le ribosome par cryo-microscopie électronique à transmission (cryo-MET). Grâce aux avancées techniques de la cryo-MET, nous avons observé pour la première fois EF-G lié au ribosome en l'absence de tout inhibiteur. Cet état particulièr d'EF-G permet de visualiser une flexibilité de son doamine III. Cette étude permet aussi de rationaliser le fonctionnement de l'antibiotique acide fusidique. Nous nous sommes ensuite intéressés aux voies de sauvetage de la synthèse protéique et plus particulièrement de la trans-traduction. Ce mécanisme fascinant permet le recyclage des ribosomes bloqués sur un ARN messager défectueux. Cette voie de sauvetage est généralement vitale ou alors indispensable pour la virulence bactérienne. Nous avons réalisé une étude structurale préliminaire de la dégradation de l'ARNm défectueux durant ce processus. Après une revue traitant du sujet, nous présentons une étude de la trans-traduction comme cible pour le développement de nouveaux antibiotiques. Pour cela, nous avons mis au point un système rapporteur avec contrôle interne de l'activité trans-traductionnelle bactérienne. Après avoir mis au point ce système et validé son utilisation, nous l'avons exploité en testant des molécules ciblant la trans-traduction. / The current PhD work brings together various studies linked to bacterial protein synthesis. The first chapter is about the origins of protein synthesis at the time of the RNA world. This theoretical work continues with the presentation of a high-resolution structure of the elongation factor G (EF-G) in complex with the ribosome by cryo-electron transmission microscopy (cryo-TEM). We describe for the first time EF-G bound to the ribosome in the absence of any inhibitor. This particular structure of EF-G displays a yet unseen positioning of its third domain, which becomes very flexible. This study helps to understand the way the antibiotic fusidic acid blocks translation. The work then switches to a study of trans-translation, the main rescuing system of stalled ribosomes in bacteria. Trans-translation is generally vital or at least necessary for bacterial virulence. We conducted a preliminary structural study on the way faulty mRNAs are degraded during this process. This is why we present a study of trans-translation as a target for the development of new antibiotics. For this we developed and validated a reporter system for trans-translation, which is used to screen molecules targeting trans-translation.