Utvecklingen av tekniken sker i snabb takt vilket gör att människors vetskap om OBA inte alltid hänger med, inte heller lagar och regler som ska skydda deras integritet. Därför är det intressant att undersöka hur effektiv marknadsföringstypen OBA är beroende av konsumenternas medvetenhet om fenomenet. Syftet är att analysera hur hög, respektive låg medvetenhet hos konsumenter om online behavioral advertising påverkar deras köpintentioner, med fokus på Generation Ys uppfattningar. Denna studie visar på samband mellan lägre medvetenhet om OBA och högre köpintentioner. Lägre medvetenhet om denna typ av marknadsföring förknippas även med en högre oro kring integriteten. / The development of technology takes place at a rapid pace, which means that people's knowledge of OBA does not always keep up, nor laws and regulations that supposed to protect their privacy. Therefore, it is interesting to investigate how effective online behavioral advertising is as a marketing strategy, based on consumers’ awareness of the phenomenon. The purpose is to analyze how a high and a low level of consumers’ awareness about OBA affects their purchase intentions, focusing on Generation Y’s perceptions.This paper reveals a connection between lower awareness of OBA and higher purchase intentions. Even a higher concern about integrity in the context is associated with lower awareness about this type of marketing.

Chez la femme, le cancer du sein est le cancer le plus fréquemment diagnostiqué. Différents traitements sont disponibles selon le sous-type tumoral. Cependant, certaines patientes sont réfractaires à ces thérapies et restent vulnérables lors de récidives. Le cancer a longtemps été défini par une division aberrante des cellules, mais aujourd'hui, il est évident que la résistance à la mort cellulaire programmée est un paramètre majeur dans l'étiologie de la maladie.Les cyclines de type D régulent le cycle cellulaire en permettant la transition de la phase G1 à la phase S. Pour cela, elles activent les kinases dépendantes des cyclines 4/6 (CDK4/6) qui phosphorylent les protéines du rétinoblastome ce qui libère le facteur de transcription E2F. La Cycline D1 (CycD1) nucléaire est donc centrale dans le contrôle du cycle. Son gène est amplifié dans les cancers humains et la moitié des patientes atteintes d'un cancer du sein ont une surexpression de CycD1. Par l’activation de CDK4, CycD1 est essentielle à l'apparition et à la progression tumorale. Ainsi, des inhibiteurs spécifiques de CDK4/6 ont été développés contre le cancer du sein. Malheureusement, certaines patientes restent insensibles à ce traitement. À ce titre, le ciblage spécifique de CycD1 pourrait représenter une alternative clinique. En effet, en plus de la régulation du cycle, CycD1 est également impliquée, indépendamment de CDK4, dans la survie des cellules cancéreuses. Cependant, aucun mécanisme de l'impact de CycD1 dans le maintien tumoral n'a été établi pour démontrer ce potentiel thérapeutique. En outre, CycD1 a été décrite dans les organes à l’âge adulte pour réguler le métabolisme du glucose et l'hématopoïèse. Par conséquent, pour éviter tout effet secondaire indésirable, nous avons décidé d’évaluer l’implication potentielle de CycD1 dans les organes adultes. Grâce au Tandem-HTRF, basé sur le transfert d'énergie entre deux anticorps, nous avons révélé la dynamique inattendue de CycD1 dans chaque organe adulte. De plus, nous avons montré que l’altération de l'expression de CycD1 conduit à une diminution des capacités de survie des cellules saines post-mitotiques.Au vu de ces limitations, nous avons développé une nouvelle approche d'ARN interférence spécifique des cellules cancéreuses appelée TAG-RNAi. Cette technologie permet de cibler CycD1 uniquement dans la tumeur afin d'épargner les cellules saines. Cette approche innovante consiste à cibler un tag présent uniquement sur l’ARNm de CycD1 des cellules cancéreuses. Ainsi, nous avons découvert que le ciblage spécifique de CycD1 induit une régression rapide et spontanée des tumeurs dépendantes des oncogènes RAS ou ERBB2. Par protéomique in vivo, j'ai découvert que lors de stress pro-apoptotiques, CycD1 cytoplasmique interagit avec la procaspase-3 et bloque son activation pour empêcher l'apoptose des cellules. Ces travaux démontrent la valeur clinique du ciblage spécifique de CycD1 dans les cancers afin d'améliorer l'efficacité des chimiothérapies.Par conséquent, il restait à déterminer comment appliquer le TAG-RNAi contre CycD1 uniquement dans les cellules cancéreuses des patientes. Puisque le tag exotique présent sur le gène Ccnd1 chez la souris nous a permis de cibler spécifiquement les cellules cancéreuses, nous avons pensé que des mutations retrouvées dans les cancers humains représentaient une option de ciblage. Ainsi, nous avons étendu le concept TAG-RNAi aux mutations somatiques caractéristiques des cancers pour cibler avec succès l'expression des mutants KRAS-G12V ou BRAF-V600E comme exemples. L'idée est donc d'identifier les mutations de Ccnd1 chez les patientes afin d'appliquer le TAG-RNAi comme une thérapie personnalisée afin d’éviter les effets secondaires. Enfin, l'expression de CycD1 représente un nouveau biomarqueur pour le cancer et les troubles liés à l'âge: de faibles taux prédisposent aux maladies dégénératives tandis que des taux élevés indiquent une susceptibilité accrue au cancer. / Breast cancer is the most frequently diagnosed cancer in women. This cancer is the leading cause of death in women aged from 35 to 65 years old. Different treatments are now available depending on tumor subtypes. However, some patients are still refractory to these therapies and are at risk of disease relapse. Cancer research has long focused on aberrant cancer cell division but today it is evident that the resistance to programmed cell death is also a major characteristic of the disease.D-type cyclins regulate cell cycle by allowing the transition from the G1-phase to the S-phase. These regulatory subunits activate the Cyclin-Dependent Kinases 4/6 (CDK4/6) that phosphorylate the retinoblastoma proteins which then release the E2F transcription factors. Nuclear Cyclin D1 (CycD1) is therefore central in the control of division. The Ccnd1 gene is amplified in human cancers and half of breast cancer patients bare an overexpression of CycD1. CycD1 is required for mammary carcinoma onset and progression in a CDK4 kinase-dependent manner. Hence, specific CDK4/6 inhibitors have been developed and authorized in the clinics against breast cancer. Unfortunately, some patients remain insensitive to this treatment. In this frame, the specific targeting of CycD1 could represent a strategic alternative in clinics to overcome these pitfalls. Indeed, in addition to cell cycle regulation with CDK4, CycD1 is also involved in CDK4-independent features of cancer cells like cell survival. However, to date, no clear mechanism for the impact of CycD1 in tumor maintenance is established to demonstrate the therapeutic value of its targeting.Moreover, recent studies have demonstrated the participation of CycD1 in adult organs to regulate glucose metabolism and hematopoiesis. As a consequence, to avoid any undesirable side effects, we decided to gauge the potential CycD1 implication in post-mitotic organs body-wide. We set up a new hypersensitive technology named Tandem-HTRF based on the energy transfer between two antibodies to reveal the unexpected dynamics of CycD1 expression in adult organ. Then, we discovered that alterations of CycD1 expression induced dramatic functional consequences on the survival capacities of healthy adult post-mitotic cells.Based on these limitations, we developed a novel RNAi approach specific to cancer cells named TAG-RNAi. This technology allows the silencing of CycD1 in cancer cells only to spare healthy cells. This innovative approach consists in the targeting of a mRNA tag only present on CycD1 from cancer cells. Using this technique, we found that the specific silencing of CycD1 induces a rapid and spontaneous regression of tumors driven by the RAS or ERBB2 oncogenes. Then, thanks to a proteomics screening in vivo, I discovered that under pro-apoptotic stresses the cytoplasmic CycD1 interacts with the procaspase-3 protein and blocks its activation to prevent cancer cell apoptosis. Altogether, my work demonstrates the clinical value of the specific targeting of CycD1 in cancers to increase the efficacy of chemotherapeutic treatments.Hence, it remained to be determined how to apply in patients RNAi against CycD1 only in cancer cells. Because the exotic tagging of its gene was instrumental in mice cancer models, we reasoned that human cancer mutations could represent such a specific tag. We have extended the concept of TAG-RNAi to somatic mutations characteristic of human cancers to successfully target the expression of KRAS-G12V or BRAF-V600E mutants as examples. The idea is therefore to identify Ccnd1 mutations in cancer patients in order to apply TAG-RNAi as a custom therapeutic approach that will manage side effects. More unanticipated, CycD1 expression represents a new biomarker for both cancer and age-related disorders: low CycD1 levels predispose to degenerative complications while high CycD1 levels indicate increased susceptibility to cancer and resistance to treatment.

Asthma is a respiratory syndrome associated with airflow limitation, bronchial hyperresponsiveness and inflammation of the airways in the lungs. Despite the ongoing research efforts, the outstanding heterogeneity displayed by the multiple forms in which this condition presents often hampers the attempts to determine and classify the phenotypic and endotypic biological structures at play, even when considering a limited assembly of asthmatic subjects. To increase our understanding of the molecular mechanisms and functional pathways that govern asthma from a systems medicine perspective, a computational workflow focused on the identification of personalized transcriptomic modules from the U-BIOPRED study cohorts, by the use of the novel MODifieR integrated R package, was designed and applied. A feature selection of candidate asthma biomarkers was implemented, accompanied by the detection of differentially expressed genes across sample categories, the production of patient-specific gene modules and the subsequent construction of a set of core disease modules of asthma, which were validated with genomic data and analyzed for pathway and disease enrichment. The results indicate that the approach utilized is able to reveal the presence of components and signaling routes known to be crucially involved in asthma pathogenesis, while simultaneously uncovering candidate genes closely linked to the latter. The present project establishes a valuable pipeline for the module-driven study of asthma and other related conditions, which can provide new potential targets for therapeutic intervention and contribute to the development of individualized treatment strategies.

O transtorno de humor associado ao transtorno de estresse pós-traumático (TEPT) tem, em geral, desfechos clínicos mais graves. Embora essa associação esteja consolidada no transtorno depressivo, esse não é o caso no transtorno bipolar (TB). Os poucos estudos realizados acerca dessa comorbidade demonstraram piora na qualidade de vida e aumento no número de tentativas de suicídio associado aos pacientes com TEPT e TB. Nenhum estudo, entretanto, avaliou o impacto do TEPT em características centrais do TB, como o número de episódios de humor ou funcionamento psicossocial. Por outro lado, estudos pré-clínicos sugerem que existe um fenômeno de sensibilização cruzada entre o TB e o TEPT. Foi proposto que a redução do brain-derived neurotrophic fator (BDNF) e alterações de marcadores inflamatórios poderiam ser mecanismos associados a esta sensibilização. Com relação a última hipótese, as alterações em marcadores inflamatórios estão bem consolidadas no TB, porém esse não é o caso no TEPT. Com a finalidade de aprofundar o estudo dessas questões, os dois primeiros estudos que compõem essa tese abordaram aspectos clínicos e biológicos relacionados a esses transtornos. O primeiro é uma metanálise e metaregressão que demonstrou que o TEPT está associado a níveis aumentados de IL-6, IL-1β, TNF-α e interferon-γ na circulação periférica. Além disso, o tempo de doença foi positivamente associado aos níveis de IL-1β, enquanto a gravidade dos sintomas foi positivamente associada aos níveis de IL-6. Esses achados podem não só apresentar um novo mecanismo biológico para explicar o fenômeno de sensibilização cruzada entre TEPT e TB, mas também abre novos horizontes na busca de novas estratégias terapêuticas e diagnósticas para o TEPT. O segundo foi um estudo caso-controle que avaliou características clínicas centrais do TB e demonstrou pela primeira vez que indivíduos com TB e comorbidade com TEPT apresentam mais episódios maníacos e pior funcionamento psicossocial. Ademais, o início dos episódios maníacos e o uso de substâncias de abuso surgiram de maneira mais precoce nesses indivíduos. Além desses dois estudos, optamos por abordar a influência da comorbidade com os transtornos ansiosos (como o TEPT) em um desfecho clínico trágico em pacientes com transtorno de humor: o suicídio. Esse estudo foi realizado em uma população diferente da do estudo clínico anterior, incluindo pacientes com depressão maior ou com TB, e foi focado em apenas um desfecho. Nosso objetivo era criar uma ferramenta que pudesse gerar um escore de probabilidade para cada paciente com transtorno de humor que refletisse o risco de tentar suicídio. Utilizando técnicas de machine learning, demonstramos que o risco de suicídio em indivíduos com transtorno de humor pode ser estimado objetivamente a partir de variáveis clínicas facilmente obtidas e variáveis demográficas. Embora tenhamos encontrado uma boa acurácia (72%) e área (area under the curve) (77%), futuros estudos podem integrar dados de variáveis de marcadores biológicos (genética, neuroimagem, neurocognição, etc.), usando também técnicas de machine learning, para atingir uma acurácia ainda maior. O uso de um instrumento objetivo é o primeiro passo na busca de um tratamento mais personalizado para aqueles pacientes com alto risco de se suicidar. / The comorbidity between mood disorders and posttraumatic stress disorder (PTSD) is associated with poorer clinical outcomes. Although this association is well established in major depressive disorder, fewer studies included patients with bipolar disorder (BD). These studies report that patients with BD and PTSD show increased number of suicide attempts and worse quality of life. However, no clinical studies so far have reported the impact of comorbid PTSD on core features of BD, such as number of mood episodes and functional impairment. On the other hand, preclinical studies showed that there is a cross-sensitization between BD and PTSD. Accordingly, it was proposed that the brain-derived neurotrophic factor (BDNF) and changes of inflammatory markers might be the biological underpinnings of this cross-sensitization. Although the changes in inflammatory markers are well established in BD, this is not the case for PTSD. In view of the above, the first two studies of this thesis addressed clinical and biological issues related to BD and PTSD. The first is a meta-analysis and metaregression study that showed increased levels of IL-6, IL-1β, TNF-α and interferon-γ in peripheral circulation among patients with PTSD. Furthermore, illness duration was positively associated with IL-1β levels, while the severity of the symptoms was positively associated with IL-6 levels. These findings may not only provide a new biological mechanism to explain the cross-sensitization between PTSD and BD, but also opens a new avenue in the search for new therapeutic targets and diagnostic strategies for PTSD. The second was a case-control study that assessed core clinical features of BD showed increased manic episodes and functional impairment among patients with BD and comorbid PTSD. In addition, those patients were younger when they started the manic episodes and substance use. Moreover, we chose to address the influence of comorbid anxiety disorders (such as PTSD) in suicide in patients with mood disorders. This study was conducted in a different population, including patients with major depressive disorder or BD, and it was focused on only one outcome. Suicide is a tragic clinical outcome, but highly preventable. Our aim was to develop a clinical tool using machine learning techniques to estimate a probability score at individual level to stratify the risk of a patient with a mood disorder attempts suicide. Therefore, our study showed that the risk of suicide in individuals with a mood disorder can be objectively estimated from easily assessed clinical and demographic variables. Although we have found a good accuracy (72%) and area under the curve (77%), future studies may integrate data from biological markers (genetic, neuroimaging, neurocognition, etc.) also using machine learning techniques to achieve a higher accuracy. This objective instrument is the first step towards a more personalized treatment for those patients at high risk of suicide.

Les moteurs de recherche, largement utilisés dans différents domaines, sont devenus la principale source d'information pour de nombreux utilisateurs. Cependant, les Systèmes de Recherche d'Information (SRI) font face à de nouveaux défis liés à la croissance et à la diversité des données disponibles. Un SRI analyse la requête soumise par l'utilisateur et explore des collections de données de nature non structurée ou semi-structurée (par exemple : texte, image, vidéo, page Web, etc.) afin de fournir des résultats qui correspondent le mieux à son intention et ses intérêts. Afin d'atteindre cet objectif, au lieu de prendre en considération l'appariement requête-document uniquement, les SRI s'intéressent aussi au contexte de l'utilisateur. En effet, le profil utilisateur a été considéré dans la littérature comme l'élément contextuel le plus important permettant d'améliorer la pertinence de la recherche. Il est intégré dans le processus de recherche d'information afin d'améliorer l'expérience utilisateur en recherchant des informations spécifiques. Comme le facteur temps a gagné beaucoup d'importance ces dernières années, la dynamique temporelle est introduite pour étudier l'évolution du profil utilisateur qui consiste principalement à saisir les changements du comportement, des intérêts et des préférences de l'utilisateur en fonction du temps et à actualiser le profil en conséquence. Les travaux antérieurs ont distingué deux types de profils utilisateurs : les profils à court-terme et ceux à long-terme. Le premier type de profil est limité aux intérêts liés aux activités actuelles de l'utilisateur tandis que le second représente les intérêts persistants de l'utilisateur extraits de ses activités antérieures tout en excluant les intérêts récents. Toutefois, pour les utilisateurs qui ne sont pas très actifs dont les activités sont peu nombreuses et séparées dans le temps, le profil à court-terme peut éliminer des résultats pertinents qui sont davantage liés à leurs intérêts personnels. Pour les utilisateurs qui sont très actifs, l'agrégation des activités récentes sans ignorer les intérêts anciens serait très intéressante parce que ce type de profil est généralement en évolution au fil du temps. Contrairement à ces approches, nous proposons, dans cette thèse, un profil utilisateur générique et sensible au temps qui est implicitement construit comme un vecteur de termes pondérés afin de trouver un compromis en unifiant les intérêts récents et anciens. Les informations du profil utilisateur peuvent être extraites à partir de sources multiples. Parmi les méthodes les plus prometteuses, nous proposons d'utiliser, d'une part, l'historique de recherche, et d'autre part les médias sociaux. / Recently, search engines have become the main source of information for many users and have been widely used in different fields. However, Information Retrieval Systems (IRS) face new challenges due to the growth and diversity of available data. An IRS analyses the query submitted by the user and explores collections of data with unstructured or semi-structured nature (e.g. text, image, video, Web page etc.) in order to deliver items that best match his/her intent and interests. In order to achieve this goal, we have moved from considering the query-document matching to consider the user context. In fact, the user profile has been considered, in the literature, as the most important contextual element which can improve the accuracy of the search. It is integrated in the process of information retrieval in order to improve the user experience while searching for specific information. As time factor has gained increasing importance in recent years, the temporal dynamics are introduced to study the user profile evolution that consists mainly in capturing the changes of the user behavior, interests and preferences, and updating the profile accordingly. Prior work used to discern short-term and long-term profiles. The first profile type is limited to interests related to the user's current activities while the second one represents user's persisting interests extracted from his prior activities excluding the current ones. However, for users who are not very active, the short-term profile can eliminate relevant results which are more related to their personal interests. This is because their activities are few and separated over time. For users who are very active, the aggregation of recent activities without ignoring the old interests would be very interesting because this kind of profile is usually changing over time. Unlike those approaches, we propose, in this thesis, a generic time-sensitive user profile that is implicitly constructed as a vector of weighted terms in order to find a trade-off by unifying both current and recurrent interests. User profile information can be extracted from multiple sources. Among the most promising ones, we propose to use, on the one hand, searching history. Data from searching history can be extracted implicitly without any effort from the user and includes issued queries, their corresponding results, reformulated queries and click-through data that has relevance feedback potential. On the other hand, the popularity of Social Media makes it as an invaluable source of data used by users to express, share and mark as favorite the content that interests them.

Oração sem sujeito é toda e qualquer oração destituída de SN sujeito, exceto nos casos em que tal SN encontra-se em elipse. Sua manifestação na língua pode se dar tanto em termos pessoais quanto impessoais. Estas incluem ocorrências essenciais, aqui chamadas de fenomenológicas e acidentais, denominadas impessoalizadas. Já aquelas se apresentam nos casos de indeterminação de agente por omissão do SN sujeito, tradicionalmente alcunhados casos de sujeito indeterminado e por meio do processo de ergativização em sua versão secundária, aquele que atua sobre verbos não causativos e tem sido porta de entrada à concretização de orações destituídas de SN sujeito no português brasileiro. Objetivamos neste trabalho a descrição de todas as estruturas apontadas, em termos de seus comportamentos morfossintáticos na língua, pois compreendemos que descrever a oração sem sujeito portuguesa é identificar contextos morfossintáticos de dispensa, em distintos graus, do SN sujeito. Para tanto, valemo-nos de um enfoque prototípico da língua, através do qual dialogamos com a natureza escalar de nosso objeto de estudo / Subject-absent sentences are all and every sentence devoid of subject Nominal Phrase (NP), except in cases when NP is in ellipse. They occur in the language on personal or impersonal terms. On impersonal terms, they include essential occurrences, here called phenomenological occurrences and accidental occurrences, here called a-personalized occurrences. While on personal terms, they appear in cases of indetermination of the agent by ommission of subject NP, also known as indeterminate subject cases, and through the ergativization process in their secondary version. This kind of ergativization process acts on non-causative verbs, and has been the basis for the construction of most sentences devoid of subject NP in Brazilian Portuguese. In this thesis, we describe all structures indicated above, in terms of their morphosyntactic behavior in the language, as we argue that to describe subject-absence sentence means to identify morphosyntactic contexts for exemption of the subject NP, in different degrees. For this goal, we make use of a prototypical approach to the language, through which we engage with the gradual nature of our object of study

Made available in DSpace on 2014-12-17T14:19:43Z (GMT). No. of bitstreams: 1 SebastiaoFF.pdf: 448629 bytes, checksum: 4ac6abf16ea8a1b338a59557d2bea8df (MD5) Previous issue date: 2006-05-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Contemporary politics have assumed new configurations both in the way they are carried out and in the content publicized. Nevertheless, some practices are unchanged since antiquity. But the advent of the media and its circumstantial molding of current society have forced politics to make some changes to adapt both to mass media and to the new social practices in liberal democracy. Given that fact, this study tried to demonstrate how power has become personalized in Campina Grande, Para?ba, Brazil, by a politician named C?ssio Cunha Lima. Through the communications media and popular manifestations, he has been trying to create a symbiosis between Micarande a Carnival party (not held in the traditional Mardi Gras week) and his own public image, elaborating a process that identifies him with that event. In that way, he hopes to appropriate the festival and project his political image by using the party as na electoral currency in his publicity campaigns / A pol?tica contempor?nea tem assumido novas configura??es tanto nas suas formas de exerc?cio como no conte?do exposto publicamente. No entanto, algumas pr?ticas continuam imut?veis desde a antiguidade. Por?m, o advento dos meios de comunica??o e sua circunstancial moldagem na sociedade atual obrigou ? pol?tica algumas modifica??es necess?rias ? adequa??o tanto dos meios massivos quanto ?s novas pr?ticas de sociabilidade na democr?tica liberal. Diante disso, o estudo aqui apresentado procura demonstrar a personaliza??o do poder, em Campina Grande (PB), pelo agente pol?tico C?ssio Cunha Lima que, atrav?s dos meios de comunica??o e de uma manifesta??o popular, busca uma simbiose entre a festa Micarande, carnaval fora de ?poca e a sua imagem p?blica pol?tica, elaborando um processo de identifica??o pessoal com o evento citado. Objetiva, com tal fato, a apropria??o do festejo e a proje??o da sua imagem pol?tica, usando-a como moeda eleitoral e pol?tica nas suas campanhas publicit?rias

Made available in DSpace on 2014-12-17T14:36:48Z (GMT). No. of bitstreams: 1 JulianaRS_DISSERT.pdf: 1219801 bytes, checksum: a4885767c4c5952babe2b1faebf29e6e (MD5) Previous issue date: 2013-08-05 / This dissertation examines the concept of the personalized teaching proposed by the physician and educator from Rio Grande do Norte Luiz Antonio dos Santos Lima, in his doctoral thesis "Mental Hygiene and Education," published in 1927. To do so, we start from the assumption that this thinker appropriated part of the educational theory formulated by ?douard Clapar?de - specifically, in the case of the teaching concepts of the personalized teaching and comprehensive education designed by the Swiss intellectual - and, considering the Brazilian social reality of early twentieth century, reframed these concepts, adapting them to the country context. To implement the proposed idea, the bibliographical study was the option chosen, and so was done through a theoretical research which had as a reference authors whose studies referred to the Brazilian historical moment in the late nineteenth and early twentieth century, our examined time frame. As for the understanding and the methodological analysis of discourse, seen as socially constructed, the Foucault postulations were studied under an analytical approach, in which the disciplinary society is analyzed from the relations of power and knowledge that exist in it. The main source of this research was the work of "Mental Hygiene and Education," published as a requirement to the obtainment of Luiz Antonio s medical degree by the Rio de Janeiro Medicine School. Thus, it was found that the conception of personalized learning to the comprehensive education of students, as proposed in the doctoral thesis of Luiz Antonio dos Santos Lima, was related to abnormalities of mental character that children could present. School education was thought in a way by the potiguar thinker that it could be applied as deep as the moral, intellectual and behavioral deviations of the individual were, making use of hygiene practices of the minds through a normalizing process towards a civilized and developed future of the Brazilian nation which would manage, watch and fix the thoughts of the school students / Esta disserta??o examina a concep??o de ensino sob medida proposta pelo m?dico e educador potiguar Luiz Antonio dos Santos Lima, em sua tese de doutoramento Hygiene Mental e Educa??o , publicada no ano de 1927. Para tanto, partimos da hip?tese de que esse pensador apropriou-se de parte da teoria educacional formulada por ?douard Clapar?de especificamente, dos conceitos de ensino sob medida e educa??o completa pensados pelo su??o e, considerando a realidade social brasileira do in?cio do s?culo XX, ressignificou esses conceitos, adaptando-os ao contexto do pa?s. Para a execu??o do proposto, optou-se pelo estudo bibliogr?fico, no qual foi feito o aporte te?rico da investiga??o, tendo como refer?ncia os autores cujos estudos remetiam ao momento hist?rico brasileiro do final do s?culo XIX e in?cio do s?culo XX, nosso recorte temporal. Quanto ? compreens?o e tratamento metodol?gico do discurso, tido como socialmente constru?do, aderiu-se ao enfoque anal?tico das postula??es foucaultianas, nas quais a sociedade disciplinar ? analisada a partir das rela??es de poder e saber nela existente. A principal fonte de pesquisa foi a obra Hygiene Mental e Educa??o , publicada como requisito da Faculdade de Medicina do Rio de Janeiro para Luiz Antonio obter o diploma de m?dico. Desse modo, constatou-se que a concep??o de ensino sob medida para a educa??o completa dos escolares, proposta na tese de doutoramento de Luiz Antonio dos Santos Lima, estava relacionada ?s anormalidades de car?ter mental que as crian?as pudessem apresentar. O ensino escolar pensado pelo potiguar seria na medida dos desvios morais, intelectuais e comportamentais do indiv?duo e faria uso das pr?ticas de higieniza??o das mentes num processo normalizador que, voltado para o futuro civilizado e desenvolvido da na??o brasileira, controlaria, vigiaria e corrigiria os pensamentos dos escolares

Acute leukemias (AL) comprise a heterogeneous group of hematologic malignancies, and individual patient responses to treatment can be difficult to predict. Monitoring of minimal residual disease (MRD) is thus very important and holds great potential for improving treatment strategies. Common MRD targets include immunoglobulin heavy chain or T-cell receptor gene rearrangements, recurrent cytogenetic abnormalities and mutations in important hematological genes. Whereas in the majority of adult acute lymphoblastic leukemia patients a suitable MRD target can be identified, in adult acute myeloid leukemia patients well-characterized targets are found in only half of cases. The identification of new specific molecular markers of leukemic blasts for MRD assessment, particularly in AML patients, is therefore highly desirable. Our aim was to develop a flexible strategy for mapping of cytogenetically identified unique clone-specific abnormalities down to the single nucleotide level and, based on the sequence, design a specific real-time PCR assay for MRD assessment in AL patients without any previously described MRD marker. Using a combination of cytogenetic (chromosome banding, chromosome microdissection), molecular cytogenetic (mFISH, mBAND) and molecular biological (next- generation sequencing, long-range...

Introduction: Together with the introduction of new therapeutic options in castration- resistant prostate cancer (CRPC), an advance in individual disease characterization is required. Since common biopsy methods are not suitable for the majority of CRPC patients, one possible solution is the liquid biopsy that is, the analysis of circulating tumor cells (CTCs) isolated from the cancer patients' blood. Methods: A method based on the immunomagnetic enrichment of CTCs and subsequent PCR detection of tumor-associated genes (AdnaTest, Qiagen) was characterized and used for the detection of CTCs in 41 CRPC patients. Each patient was screened at the time of CRPC diagnosis and after the 3rd cycle of docetaxel therapy. A panel of genes associated with therapeutic decision-making was established and validated. Quantitative PCR (qPCR) method on a BioMark platform (Fluidigm, USA) was used to determine the expression of the gene panel in the CTC-enriched and primary tumor samples and the results were analyzed. Results: CTCs were found in 85% and 45% of CRPC patients before and during the therapy, respectively. The presence of CTCs, as well as EGFR and AR PCR fragments, was associated with a decreased sPSA response and lower survival. The gene expression of the CTC- enriched and primary tumor samples differed...