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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
201

A computational model for studying L1’s effect on L2 speech learning

January 2018 (has links)
abstract: Much evidence has shown that first language (L1) plays an important role in the formation of L2 phonological system during second language (L2) learning process. This combines with the fact that different L1s have distinct phonological patterns to indicate the diverse L2 speech learning outcomes for speakers from different L1 backgrounds. This dissertation hypothesizes that phonological distances between accented speech and speakers' L1 speech are also correlated with perceived accentedness, and the correlations are negative for some phonological properties. Moreover, contrastive phonological distinctions between L1s and L2 will manifest themselves in the accented speech produced by speaker from these L1s. To test the hypotheses, this study comes up with a computational model to analyze the accented speech properties in both segmental (short-term speech measurements on short-segment or phoneme level) and suprasegmental (long-term speech measurements on word, long-segment, or sentence level) feature space. The benefit of using a computational model is that it enables quantitative analysis of L1's effect on accent in terms of different phonological properties. The core parts of this computational model are feature extraction schemes to extract pronunciation and prosody representation of accented speech based on existing techniques in speech processing field. Correlation analysis on both segmental and suprasegmental feature space is conducted to look into the relationship between acoustic measurements related to L1s and perceived accentedness across several L1s. Multiple regression analysis is employed to investigate how the L1's effect impacts the perception of foreign accent, and how accented speech produced by speakers from different L1s behaves distinctly on segmental and suprasegmental feature spaces. Results unveil the potential application of the methodology in this study to provide quantitative analysis of accented speech, and extend current studies in L2 speech learning theory to large scale. Practically, this study further shows that the computational model proposed in this study can benefit automatic accentedness evaluation system by adding features related to speakers' L1s. / Dissertation/Thesis / Doctoral Dissertation Speech and Hearing Science 2018
202

Clonagem, expressão, purificação e caracterização das proteínas do capsídio viral do papilomavírus humano (HPV) / Cloning, expression, purification and characterization of human papillomavirus (HPV) capsid proteins

Chaves, Ágtha de Alencar Muniz 17 December 2012 (has links)
O Câncer Cervical é um importante problema de saúde pública, causando aproximadamente 270 milhões de mortes anuais. Atualmente, esse câncer é o segundo mais comum em mulheres no mundo, com os maiores índices de incidência ocorrendo nos países em desenvolvimento. O Câncer cervical tem como agente etiológico o Papilomavírus Humano (HPV). O vírus possui DNA circular duplo com genes que codificam oito proteínas, E1, E2, E4, E5, E6, E7 (não estruturais), e L1 e L2 (estruturais) que formam o capsídio viral. A proteína L1 quando produzida em sistema heterólgo de expressão tem a capacidade de auto-arranjo em partículas semelhantes ao vírus chamadas de VLPs (\"Vírus like Particles\"), que são a base das vacinas profiláticas disponíveis, Gardasil® e Cervarix®. Neste trabalho, foram produzidas VLPs da proteína L1 do HPV-16 na levedura metilotrófica Pichia pastoris utilizando dois tipos de vetores de expressão para leveduras, um epissomal e outro integrativo, para os trabalhos de purificação. Inicialmente as amostras obtidas ao final da purificação apresentaram degradação e agregação da proteína L1, além de contaminantes. O protocolo de purificação foi modificado e as amostras obtidas no final do processo de purificação não apresentaram degradação e nem agregação da proteína L1, embora ainda tenha sido detectada a presença de contaminantes e, portanto, as amostras obtidas estavam semi-purificadas. Uma segunda abordagem para o desenvolvimento de uma vacina alternativa foi realizada, na qual foram produzidos candidatos vacinais baseados na proteína L2 do Papilomavírus Humano (L2 do HPV-16, L2 do HPV-18 e L2 Multimérica), e também foram expressas proteínas fusionadas ao domínio ZZ de Staphylococcus aureus, utilizado neste caso como adjuvante. Em geral as proteínas de fusão, ainda que apresentando a fusão em sua forma funcional, geraram uma fraca indução de anticorpos IgG e de anticorpos neutralizantes. Pode-se observar uma produção de anticorpos neutralizantes contra pseudovírus homólogos e heterólogos que dependeu da combinação com os adjuvantes utilizados. Numa tentativa de maximizar a eficiência imunológica dos antígenos utilizados, um novo ensaio de imunização foi realizado com uma formulação conjunta contendo três proteínas (L2 do HPV-16, L2 do HPV-18 e L2 Multimérica), sendo também avaliadas as propriedades de três adjuvantes. A combinação da formulação vacinal com os adjuvantes gerou altos níveis de anticorpos L2-específicos, destacando-se as formulações com o hidróxido de alumínio/MPLA e com a vacina celular Pertussis low. Com a utilização desses adjuvantes, os níveis de anticorpos permaneceram elevados a longo termo. Pode-se observar a imunogenicidade de cada um dos antígenos dependeu de sua formulação com os adjuvantes testados. / Cervical cancer is one of the most important problems of public health, causing nearly 270 million deaths annually. Currently, cervical cancer is the second more common type in women worldwide and the highest incidences occuring in developing countries. Human papillomavirus (HPV) are the ethiologic agents of cervical cancer. HPV have a double-stranded circular DNA genome encoding eight viral proteins, E1, E2, E4, E5, E6, E7 (non-structural), and L1, L2 (structural), the last ones forming the viral capsid. L1 protein expressed in heterologous systems self-assembles into VLPs (\"Virus like Particles\"), the base of prophylactic vaccines available commercially, Gardasil and Cervarix. In this work, we produced VLPs of HPV-16 L1 protein in the methylotrophic yeast Pichia pastoris for purification assays. Initially, samples obtained from purification presented degradation and aggregation of L1 protein and also contaminants. The purification protocol was modified and samples obtained in the new process did not present degradation nor aggregation but the presence of some contaminants could still be detected. Therefore, samples obtained were semi-purified. A second approach to the development of an alternative vaccine was performed with the production of vaccine candidates based on the HPV L2 protein (HPV-16 L2, HPV-18 L2 and Multimeric L2) and we also expressed the same proteins fused to Staphyloccocus aureus ZZ domain, using it as an adjuvant. In general, the fused proteins induced low antibodies titer and low neutralizing antibodies titer when compared to other formulations. Neutralizing antibodies elicited against homologous and heterologous pseudovirus depended on the adjuvant used. In another approach, trying to enhance immunologic antigen efficiencies, an immunization assay was performed with a formulation containing L2 HPV- 16, L2 HPV-18 and Multimeric L2 and the properties of three adjuvants were assessed. The vaccine formulations adjuvanted with alum/MPLA and cellular Pertussis low vaccine induced the highest levels of L2-specific antibodies. In addition, the usage of adjuvants maintained the antibody levels in the long term. The immunogenicity of each antigen depends on the adjuvant combination used.
203

Kommunikationseffektivitet och kommunikationsstrategier för L1- och L2-talare i referentiella problemlösningsuppgifter / Communication effciency and communicative strategies for L1 and L2-speakers in referential communication tasks

Solberg, Jon January 2004 (has links)
<p>This thesis examines and measures differences in effciency between L1- and L2 language use for solving referential problems. Quantitative measures used in the study were time and error frequency. Qualitative measures, such as how the tasks and the participants own performance were experienced, were measured by an post interview and two questionaires. </p><p>Two different tasks, a sorting task and a construction task, in which each informant was given the role as a constructor or instructor, were used for data gathering. A total of 20 dyads, divided in two language groups (English and Swedish) participated in the study. </p><p>The results show large differences between the two language groups in respect to time for solving the two tasks. For the construction task, these were mainly due to different communication strategies used for error handling. In the sorting task a clear learning effect can be observed for the L2-groups which, in effect, makes the L2 users solve the sorting task almost as fast as the L1 groups, after an initial learning period. However, the informants in the L2 groups generally referred to the objects used in this task by describing peripheral characteristics of these objects. They also showed more signs of uncertainty and hesitation in the actual dialogue situation. However, no differences in error frequency could be found between the two language groups. </p><p>Differences in role-taking between the language groups were also made apparent in the study. These differences became especially clear for the L2 groups in the construction task.</p>
204

On the Riemannian geometry of Seiberg-Witten moduli spaces

Becker, Christian January 2005 (has links)
<p>In this thesis, we give two constructions for Riemannian metrics on Seiberg-Witten moduli spaces. Both these constructions are naturally induced from the L2-metric on the configuration space. The construction of the so called quotient L2-metric is very similar to the one construction of an L2-metric on Yang-Mills moduli spaces as given by Groisser and Parker. To construct a Riemannian metric on the total space of the Seiberg-Witten bundle in a similar way, we define the reduced gauge group as a subgroup of the gauge group. We show, that the quotient of the premoduli space by the reduced gauge group is isomorphic as a U(1)-bundle to the quotient of the premoduli space by the based gauge group. The total space of this new representation of the Seiberg-Witten bundle carries a natural quotient L2-metric, and the bundle projection is a Riemannian submersion with respect to these metrics. We compute explicit formulae for the sectional curvature of the moduli space in terms of Green operators of the elliptic complex associated with a monopole. Further, we construct a Riemannian metric on the cobordism between moduli spaces for different perturbations. The second construction of a Riemannian metric on the moduli space uses a canonical global gauge fixing, which represents the total space of the Seiberg-Witten bundle as a finite dimensional submanifold of the configuration space.</p> <p>We consider the Seiberg-Witten moduli space on a simply connected K&auml;uhler surface. We show that the moduli space (when nonempty) is a complex projective space, if the perturbation does not admit reducible monpoles, and that the moduli space consists of a single point otherwise. The Seiberg-Witten bundle can then be identified with the Hopf fibration. On the complex projective plane with a special Spin-C structure, our Riemannian metrics on the moduli space are Fubini-Study metrics. Correspondingly, the metrics on the total space of the Seiberg-Witten bundle are Berger metrics. We show that the diameter of the moduli space shrinks to 0 when the perturbation approaches the wall of reducible perturbations. Finally we show, that the quotient L2-metric on the Seiberg-Witten moduli space on a K&auml;hler surface is a K&auml;hler metric.</p> / <p>In dieser Dissertationsschrift geben wir zwei Konstruktionen Riemannscher Metriken auf Seiberg-Witten-Modulr&auml;umen an. Beide Metriken werden in nat&uuml;rlicher Weise durch die L2-Metrik des Konfiguartionsraumes induziert. Die Konstruktion der sogenannten Quotienten-L2-Metrik entspricht der durch Groisser und Parker angegebenen Konstruktion einer L2-Metrik auf Yang-Mills-Modulr&auml;umen. Zur Konstruktion einer Quotienten-Metrik auf dem Totalraum des Seiberg-Witten-B&uuml;ndels f&uuml;hren wir die sogenannte reduzierte Eichgruppe ein. Wir zeigen, dass der Quotient des Pr&auml;modulraumes nach der reduzierten Eichgruppe als U(1)-B&uuml;ndel isomorph ist zu dem Quotienten nach der basierten Eichgruppe. Dadurch tr&auml;gt der Totalraum des Seiberg-Witten B&uuml;ndels eine nat&uuml;rliche Quotienten-L2-Metrik, bzgl. derer die B&uuml;ndelprojektion eine Riemannsche Submersion ist. Wir berechnen explizite Formeln f&uuml;r die Schnittr&uuml;mmung des Modulraumes in Ausdr&uuml;cken der Green-Operatoren des zu einem Monopol geh&ouml;rigen elliptischen Komplexes. Ferner konstruieren wir eine Riemannsche Metrik auf dem Kobordismus zwischen Modulr&auml;umen zu verschiedenen St&ouml;rungen. Die zweite Konstruktion einer Riemannschen Metrik auf Seiberg-Witten-Modulr&auml;umen benutzt eine kanonische globale Eichfixierung, verm&ouml;ge derer der Totalraum des Seiberg-Witten-B&uuml;ndels als endlich-dimensionale Untermannigfaltigkeit des Konfigurationsraumes dargestellt werden kann.</p> <p>Wir betrachten speziell die Seiberg-Witten-Modulr&auml;ume auf einfach zusammenh&auml;ngenden K&auml;hler-Mannigfaltigkeiten. Wir zeigen, dass der Seiberg-Witten-Modulraum (falls nicht-leer) im irreduziblen Fall ein komplex projektiver Raum its und im reduziblen Fall aus einem einzelnen Punkt besteht. Das Seiberg-Witten-B&uuml;ndel l&auml;&szlig;t sich mit der Hopf-Faserung identifizieren. Die L2-Metrik des Modulraumes auf der komplex projektiven Fl&auml;che CP2 (mit einer speziellen Spin-C-Struktur) ist die Fubini-Study-Metrik; entsprechend sind die Metriken auf dem Totalraum Berger-Metriken. Wir zeigen, dass der Durchmesser des Modulraumes gegen 0 konvergiert, wenn die St&ouml;rung sich dem reduziblen Fall n&auml;hert. Schlie&szlig;lich zeigen wir, dass die Quotienten-L2-Metrik auf dem Seiberg-Witten-Modulraum einer K&auml;hlerfl&auml;che eine K&auml;hler-Metrik ist.</p>
205

Blindness and Second Language Acquisition : Studies of Cognitive Advantages in Blind L1 and L2 speakers

Smeds, Helena January 2015 (has links)
The aim of this study is to investigate whether blind individuals display cognitive advantages over sighted individuals with regard to second language acquisition. Previous studies from neuropsychology have indicated that this is the case. It has been found that blind L1 speakers can compensate for loss of vision by developing better perceptual and cognitive skills compared to sighted individuals, skills that are highly relevant to language acquisition. These studies do not, however, investigate blind L2 speakers, for whom it is not clear whether these advantages are also found.  In all, 80 adults participated in the study: 40 L2 speakers of Swedish (11 early blind, 9 late blind, 20 sighted, AO&lt;18) and a matching group and subgroups of L1 speakers. These speakers underwent tests on speech perception in noise, accentedness in an L2 and memory functions. The results revealed that L2 speakers are at a great disadvantage perceiving speech in noise compared to L1 speakers, and that there was no advantage associated with blindness. In the L1 speakers group, however, the results revealed that the early blind had advantages compared to the late blind and sighted in white noise, but that both blind groups were more negatively affected by babble noise than the sighted. The results in relation to accentedness in an L2 revealed that there were no advantages associated with blindness. The results further revealed there were no advantages associated with blindness on the episodic memory test. The results did, however, reveal that the early blind performed significantly better than the late blind and sighted on all phonological short-term memory tests and that both the early and late blind were significantly better than the sighted on recognition memory for new words, irrespective of language background. The conclusion is that blindness is associated with advantages in, for example, ability to learn new words and syntax, acquisition rate, ultimate L2 attainment, and language aptitude.
206

Les aspirations intrusives dans l’anglais des apprenants francophones / Intrusive tokens of aspiration in French learners’ L2 English

Exare, Christelle 31 January 2017 (has links)
Cette thèse décrit les aspirations intrusives, saillantes mais labiles, souvent représentées par /h/ ou [h], dans l’anglais L2 des francophones (par exemple : I hate pasta au lieu de I ate pasta). Le phonème /h/ est débile dans les langues indo-européennes. Historiquement, la consonne subit une lénition progressive, avec une forte variation linguistique et extralinguistique (diatopique, diastratique et diachronique). La fricative glottale /h/ à l’attaque de mot en anglais L1 est caractérisée par i) l’ouverture de la glotte et ii) la configuration supraglottale de la voyelle suivante. Dans cette étude, les réalisations des attaques de mot en anglais sont étudiées à partir de trois sortes de données : i) un texte lu par 8 anglophones et 10 francophones, ii) la parole spontanée de 25 francophones et iii) un test de perception passé par 30 francophones. La fréquence d’apparition des aspirations intrusives montre une forte variabilité inter- et intra-locuteurs. Elles sont retrouvées exclusivement i) en position initiale absolue ou ii) après un phone vocalique. Une pause, une glottalisation ou une aspiration sont trois procédés qui conduisent à augmenter l’écart temporel entre deux voyelles en hiatus. Une glottalisation ou une aspiration ont en commun de correspondre à une tension glottale. Les aspirations illicites semblent être des traces d’hypercorrection qui pourraient être dues i) à une assimilation incomplète du contraste phonétique [ʔ] ~ [h] de l’anglais, ii) à la réparation phonologique facultative de *#V, iii) à un geste de constriction glottale n’atteignant pas sa cible (glottalisation inchoative) et à un geste intrusif d’ouverture glottale. La correction phonétique proposée par le professeur recherche la prise de conscience par l’apprenant i) du contrôle de la glotte pour l’aspiration, la glottalisation et le maintien d’un voisement modal en frontière morphologique, et ii) des particularités syllabiques du français et de l’anglais qui font des frontières de mot des points d’achoppement potentiels en anglais L2. / This dissertation describes some salient, yet variable, intrusive tokens of aspiration, often represented by /h/ or [h], in French learners’ L2 English productions (e.g. : I hate pasta instead of I ate pasta). The phoneme /h/ is weak in Indo-European languages. Historically, the consonant has undergone progressive lenition and exhibits strong intralinguistic and extralinguistic --diachronic, dialectal and stylistic-- variation. The glottal fricative /h/ at English word onsets is characterised by i) an open glottis and ii) the supraglottal configuration of the following vowel. In the present study, the onsets of English words are analysed in three types of data: i) a text read by 8 native English speakers and 10 French learners of English, ii) spontaneous speech elicited from 25 French learners and iii) a perception test taken by 30 French-speaking students. The frequency of intrusive tokens of aspiration at L2 English word onsets shows high inter- and intra-speaker variability. Importantly, however, they only surface i) in strict initial position or ii) after a vocalic sound. A pause, some glottalisation or some aspiration are three processes that contribute to increasing the time span between two vowels in a hiatus context. Glottalisation and aspiration both correspond to glottal tension. Illicit tokens of aspiration can be considered as occurrences of hypercorrection, which may result from : i) incomplete assimilation of the English [ʔ] ~ [h] contrast, ii) optional phonological repair of *#V, iii) a glottal constriction gesture that fails to reach its target (i.e. inchoative glottalisation) and an intrusive gesture of glottal opening. Phonetic corrective feedback in L2 learning is proposed. It aims at raising the learner’s awareness of i) glottal control for aspiration, glottalisation, and continuous modal voicing across word boundaries and ii) some syllabic specificities of French and English that make word boundaries potential stumbling blocks in French learners’ L2 English.
207

DIAALE : Conception, implémentation et évaluation d’un dispositif en ligne d’aide à l’apprentissage de la lecture scientifique en anglais langue étrangère. / DIAALE : Design, implementation and evaluation of an online learning aid for scientific reading in English as a Foreign Language

Colina, Zulimar 19 June 2017 (has links)
La thèse se propose de documenter les domaines du développement de la compréhension écrite en L2 chez des publics de non-spécialistes et de l’intégration des technologies de l’information et de la communication pour l’enseignement en contexte vénézuélien. Pour ce faire, la recherche s’appuie sur la conception, la mise en œuvre et l’analyse de deux dispositifs d’apprentissage de l’anglais comme langue étrangère, distanciels, intégrant des outils collaboratifs dans le contexte de la faculté d’ingénierie de l’université de Carabobo au Vénézuéla. Ces deux dispositifs permettent le recueil de données de recherche et de données écologiques, qui sont structurées en corpus puis traitées. A partir de ces données hétérogènes, sont étudiés particulièrement les processus de collaboration entre élèves-ingénieurs dans des tâches de lecture en anglais L2, le développement des compétences en compréhension écrite et l’utilisation des dispositifs électroniques mobiles pendant ces tâches collaboratives. / This thesis proposes to document the fields of the development of the writing comprehension in L2 among non-specialist publics and the integration of the information and communication technologies for the teaching in Venezuelan context. In order to do this, this research is based on the design, implementation and analysis of two devices of learning English as a foreign language, distant, integrating collaborative tools in the context of the faculty of engineering of the University of Carabobo in Venezuela. These two devices allow the collection of researching data and ecological data, which are structured in corpus and then processed. From these heterogeneous data, the collaborative processes between student-engineers in L2 reading tasks, the development of written comprehension skills and the use of mobile electronic devices during these collaborative tasks
208

Synthèse d’observateurs intervalles à entrées inconnues pour les systèmes linéaires à paramètres variants / Unknown input interval observer for linear parameter varying systems

Ellero, Nicolas 12 July 2018 (has links)
Cette thèse porte sur la conception d’une classe particulière d’estimateurs d'état, les observateurs intervalles. L’objectif est d’estimer de manière garantie, les bornes supérieure et inférieure de l’ensemble admissible de l'état d’un système, à chaque instant de temps. L’approche considérée repose sur la connaissance a priori du domaine d’appartenance, supposé borné, des incertitudes du système (incertitudes de modélisation, perturbations, bruits, etc). Une classe d'observateurs intervalles à entrées inconnues est proposée pour la classe des systèmes Linéaires à Paramètres Variants (LPV). La synthèse des paramètres de l’observateur repose sur la résolution d’un problème d’optimisation sous contraintes de type inégalités matricielles linéaires (LMI) permettant de garantir simultanément les conditions d’existence de l’observateur ainsi qu’un niveau de performance, soit dans un contexte énergie, soit dans un contexte amplitude ou soit dans un contexte mixte énergie/amplitude. Plus particulièrement, la performance de l'observateur repose sur une technique de découplage pour annuler les effets des entrées inconnues et une technique d’optimisation destinée à minimiser, au sens de critères de type gain L2et/ou gain L∞, les effets des perturbations sur la largeur totale de l’enveloppe de l'état du système LPV. La méthodologie de synthèse proposée est illustrée sur un exemple académique. Enfin, la méthodologie est appliquée au cas de la phase d’atterrissage du véhicule spatial HL20, sous des conditions de simulations réalistes. / This thesis addresses the design of a class of estimator, named interval obser-ver, which evaluates in a guaranteed way, a set for the state of the system at each instant of time. The proposed approach is based on a priori knowledge of bounded sets for the system uncertainties (modeling uncertainties, disturbances, noise, etc.). A methodology to design an interval observer is proposed for the class of Linear Parameter Varying (LPV) Systems. The feasibility of the latter is based on the resolution of linear Matrix Inequalities (LMI) constraints allowing to simultaneously get the existence conditions of the intervalobserver and a certain level of a priori given performance for the state estimation of the system. Specifically, the performance of the estimates is based on a decoupling technique to avoid the effects of unknown inputs and an optimization technique to minimize, in the L2 and/or L∞ gain sense, the effects of disturbances on the estimated interval length for the state of the LPV system. The design methodology is illustrated on academic examples.Finally, the methodology is applied on the landing phase of the HL20 shuttle.
209

Kommunikationseffektivitet och kommunikationsstrategier för L1- och L2-talare i referentiella problemlösningsuppgifter / Communication effciency and communicative strategies for L1 and L2-speakers in referential communication tasks

Solberg, Jon January 2004 (has links)
This thesis examines and measures differences in effciency between L1- and L2 language use for solving referential problems. Quantitative measures used in the study were time and error frequency. Qualitative measures, such as how the tasks and the participants own performance were experienced, were measured by an post interview and two questionaires. Two different tasks, a sorting task and a construction task, in which each informant was given the role as a constructor or instructor, were used for data gathering. A total of 20 dyads, divided in two language groups (English and Swedish) participated in the study. The results show large differences between the two language groups in respect to time for solving the two tasks. For the construction task, these were mainly due to different communication strategies used for error handling. In the sorting task a clear learning effect can be observed for the L2-groups which, in effect, makes the L2 users solve the sorting task almost as fast as the L1 groups, after an initial learning period. However, the informants in the L2 groups generally referred to the objects used in this task by describing peripheral characteristics of these objects. They also showed more signs of uncertainty and hesitation in the actual dialogue situation. However, no differences in error frequency could be found between the two language groups. Differences in role-taking between the language groups were also made apparent in the study. These differences became especially clear for the L2 groups in the construction task.
210

Clonagem, expressão, purificação e caracterização das proteínas do capsídio viral do papilomavírus humano (HPV) / Cloning, expression, purification and characterization of human papillomavirus (HPV) capsid proteins

Ágtha de Alencar Muniz Chaves 17 December 2012 (has links)
O Câncer Cervical é um importante problema de saúde pública, causando aproximadamente 270 milhões de mortes anuais. Atualmente, esse câncer é o segundo mais comum em mulheres no mundo, com os maiores índices de incidência ocorrendo nos países em desenvolvimento. O Câncer cervical tem como agente etiológico o Papilomavírus Humano (HPV). O vírus possui DNA circular duplo com genes que codificam oito proteínas, E1, E2, E4, E5, E6, E7 (não estruturais), e L1 e L2 (estruturais) que formam o capsídio viral. A proteína L1 quando produzida em sistema heterólgo de expressão tem a capacidade de auto-arranjo em partículas semelhantes ao vírus chamadas de VLPs (\"Vírus like Particles\"), que são a base das vacinas profiláticas disponíveis, Gardasil® e Cervarix®. Neste trabalho, foram produzidas VLPs da proteína L1 do HPV-16 na levedura metilotrófica Pichia pastoris utilizando dois tipos de vetores de expressão para leveduras, um epissomal e outro integrativo, para os trabalhos de purificação. Inicialmente as amostras obtidas ao final da purificação apresentaram degradação e agregação da proteína L1, além de contaminantes. O protocolo de purificação foi modificado e as amostras obtidas no final do processo de purificação não apresentaram degradação e nem agregação da proteína L1, embora ainda tenha sido detectada a presença de contaminantes e, portanto, as amostras obtidas estavam semi-purificadas. Uma segunda abordagem para o desenvolvimento de uma vacina alternativa foi realizada, na qual foram produzidos candidatos vacinais baseados na proteína L2 do Papilomavírus Humano (L2 do HPV-16, L2 do HPV-18 e L2 Multimérica), e também foram expressas proteínas fusionadas ao domínio ZZ de Staphylococcus aureus, utilizado neste caso como adjuvante. Em geral as proteínas de fusão, ainda que apresentando a fusão em sua forma funcional, geraram uma fraca indução de anticorpos IgG e de anticorpos neutralizantes. Pode-se observar uma produção de anticorpos neutralizantes contra pseudovírus homólogos e heterólogos que dependeu da combinação com os adjuvantes utilizados. Numa tentativa de maximizar a eficiência imunológica dos antígenos utilizados, um novo ensaio de imunização foi realizado com uma formulação conjunta contendo três proteínas (L2 do HPV-16, L2 do HPV-18 e L2 Multimérica), sendo também avaliadas as propriedades de três adjuvantes. A combinação da formulação vacinal com os adjuvantes gerou altos níveis de anticorpos L2-específicos, destacando-se as formulações com o hidróxido de alumínio/MPLA e com a vacina celular Pertussis low. Com a utilização desses adjuvantes, os níveis de anticorpos permaneceram elevados a longo termo. Pode-se observar a imunogenicidade de cada um dos antígenos dependeu de sua formulação com os adjuvantes testados. / Cervical cancer is one of the most important problems of public health, causing nearly 270 million deaths annually. Currently, cervical cancer is the second more common type in women worldwide and the highest incidences occuring in developing countries. Human papillomavirus (HPV) are the ethiologic agents of cervical cancer. HPV have a double-stranded circular DNA genome encoding eight viral proteins, E1, E2, E4, E5, E6, E7 (non-structural), and L1, L2 (structural), the last ones forming the viral capsid. L1 protein expressed in heterologous systems self-assembles into VLPs (\"Virus like Particles\"), the base of prophylactic vaccines available commercially, Gardasil and Cervarix. In this work, we produced VLPs of HPV-16 L1 protein in the methylotrophic yeast Pichia pastoris for purification assays. Initially, samples obtained from purification presented degradation and aggregation of L1 protein and also contaminants. The purification protocol was modified and samples obtained in the new process did not present degradation nor aggregation but the presence of some contaminants could still be detected. Therefore, samples obtained were semi-purified. A second approach to the development of an alternative vaccine was performed with the production of vaccine candidates based on the HPV L2 protein (HPV-16 L2, HPV-18 L2 and Multimeric L2) and we also expressed the same proteins fused to Staphyloccocus aureus ZZ domain, using it as an adjuvant. In general, the fused proteins induced low antibodies titer and low neutralizing antibodies titer when compared to other formulations. Neutralizing antibodies elicited against homologous and heterologous pseudovirus depended on the adjuvant used. In another approach, trying to enhance immunologic antigen efficiencies, an immunization assay was performed with a formulation containing L2 HPV- 16, L2 HPV-18 and Multimeric L2 and the properties of three adjuvants were assessed. The vaccine formulations adjuvanted with alum/MPLA and cellular Pertussis low vaccine induced the highest levels of L2-specific antibodies. In addition, the usage of adjuvants maintained the antibody levels in the long term. The immunogenicity of each antigen depends on the adjuvant combination used.

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