Action anti-leucémique des inhibiteurs de la méthylation de l’ADN et de la déacétylation des histones

Les gènes suppresseurs de tumeurs (TSGs) contrôlent la prolifération cellulaire et leur inactivation joue un rôle important dans la leucémogénèse. Deux mécanismes épigénétiques majeurs sont impliqués dans la répression des TSGs: 1- la méthylation de l’ADN et 2- la déacétylation des histones des chromosomes. On les dit épigénétiques car ils n’affectent pas la séquence de l’ADN. Ces phénomènes sont réversibles, faisant donc d’eux des cibles thérapeutiques de choix. Dans le cadre de cette thèse, nous avons évalué le potentiel chimiothérapeutique de différents agents qui visent ces mécanismes épigénétiques et nous les avons administrés seuls et en combinaison dans le but d’améliorer leur efficacité. La 5-aza-2’-désoxycytidine (5-Aza-CdR) est un inhibiteur de la méthylation de l’ADN qui permet la ré-expression des TSGs. Cet agent s’est avéré efficace contre certaines maladies hématologiques et est d’ailleurs approuvé aux États-Unis dans le traitement du syndrome myélodysplasique depuis 2006. Cependant, le protocole d’administration optimal de cet agent, en termes de doses et de durée, n’est toujours pas établi. Nos recherches suggèrent que le celui-ci devrait être plus intensif que ce que rapporte la littérature. Les inhibiteurs des déacétylases des histones (HDACi) ont également montré une activité antinéoplasique intéressante. De récentes recherches ont montré que la combinaison d’agents ciblant à la fois la méthylation de l’ADN et la déacétylation des histones produit une réactivation synergique des TSGs, ce à quoi nous nous sommes intéressé. Nous avons observé que la co-administration d’un HDACi avec la 5-Aza-CdR potentialise son action anti-leucémique. Il est aussi possible d’augmenter l’activité de la 5-Aza-CdR en inhibant sa dégradation par l’enzyme cytidine (CR) désaminase. Nous avons observé que la co-administration du zebularine, un inhibiteur de la CR désaminase, avec la 5-Aza-CdR accroît son efficacité. Le zebularine est aussi un inhibiteur de la méthylation de l’ADN, ce qui pourrait contribuer à la potentialisation de la réponse anti-leucémique observée lors de la co-administration de ces deux agents. En résumé, il est possible d’augmenter l’efficacité anti-leucémique de la 5-Aza-CdR en : 1- intensifiant son protocole d’administration, en termes de doses et de durée, 2- la combinant avec un HDACi, et 3- diminuant sa dégradation par la CR désaminase. L’utilisation de ces résultats précliniques dans l’élaboration de protocoles cliniques pourrait être bénéfique à beaucoup de patients.

Le transfert des connaissances pour prévenir les chutes chez des personnes âgées en centre hospitalier cardiovasculaire aigu

Rapport de stage présenté à la Faculté des sciences infirmières en vue de l'obtention du grade de Maître ès sciences (M.Sc.) option expertise-conseil en soins infirmiers

Augmenter la vitesse d’injection de la cocaïne favorise l’apparition de comportements de consommation caractéristiques de la toxicomanie

Nombreux individus vont expérimenter avec les drogues d’abus, mais peu vont devenir toxicomanes. Plusieurs facteurs sont impliqués dans la transition d’un usage récréatif à l’addiction. Les drogues, les conditionnements et les voies d’administration qui mènent à l’augmentation rapide du taux drogue dans le cerveau favorisent cette évolution. La raison est méconnue. Nous avons émis l’hypothèse que l’injection rapide de drogue promeut des changements dans le cerveau qui mènent à l’augmentation de la consommation et de la motivation à obtenir la drogue. Nous avons comparé la consommation lors de conditions à ratio fixe (FR) et à ratio progressif (PR) chez des rats s’auto-administrant la cocaïne administrée par voie intraveineuse (i.v.) en 5 ou 90 secondes (s). Tous les rats ont été entrainés à peser sur un levier afin de s’auto administrer des injections de cocaïne de 0.25 ou 0.5 mg/kg par voie intraveineuse injectée en 5 s sous FR avant d’être divisés en groupes s’auto administrant la cocaïne injectée en 5 ou 90 s pendant 1 heure (h)/session. Pour étudier les différences potentielles en consommation, l’accès à la cocaïne à été augmenté à 6 h/session. Les différences en motivation ont été détectées par l’auto administration de la cocaïne sous PR en fonction de la dose et de la vitesse d’infusion. L’accès à la drogue pendant 1 h/session n’a pas influencé la consommation. Lorsque l’accès a été prolongé à 6 h, tous les animaux ont augmenté leur consommation, mais l’augmentation était plus prononcée chez les rats s’injectant la cocaïne en 5 s. De plus, la vitesse d’injection a influencé la motivation pour obtenir la drogue. Lors de conditions à PR, la courbe dose-réponse pour le nombre d’infusions prises a été déplacée vers le haut pour les rats s’auto administrant des injections de cocaïne en 5 s versus 90 s. De plus, des différences qualitatives on été observées en PR. La consommation de cocaïne des rats s’injectant des infusions en 5 s était dépendante de la dose, tandis que les rats s’auto administrant la drogue en 90 s ont pris la même quantité de drogue, peu importe la dose. Finalement, les rats s’auto administrant des infusions de cocaïne 0.5 mg/kg en 5 s ont consommé plus de cocaïne que les rats prenant des infusions en 90 s, peu importe si elle était injectée en 5 ou 90 s le jour du test. Ainsi, nos résultats montrent que l’injection rapide de drogue dans le cerveau mène à l’augmentation de la consommation et de la motivation pour obtenir la cocaïne, deux symptômes qui caractérisent la toxicomanie.

Matrix based Key Generation to Enhance Key Avalanche in Advanced Encryption Standard

In symmetric block ciphers, substitution and diffusion operations are performed in multiple rounds using sub-keys generated from a key generation procedure called key schedule. The key schedule plays a very important role in deciding the security of block ciphers. In this paper we propose a complex key generation procedure, based on matrix manipulations, which could be introduced in symmetric ciphers. The proposed key generation procedure offers two advantages. First, the procedure is simple to implement and has complexity in determining the sub-keys through crypt analysis. Secondly, the procedure produces a strong avalanche effect making many bits in the output block of a cipher to undergo changes with one bit change in the secret key. As a case study, matrix based key generation procedure has been introduced in Advanced Encryption Standard (AES) by replacing the existing key schedule of AES. The key avalanche and differential key propagation produced in AES have been observed. The paper describes the matrix based key generation procedure and the enhanced key avalanche and differential key propagation produced in AES. It has been shown that, the key avalanche effect and differential key propagation characteristics of AES have improved by replacing the AES key schedule with the Matrix based key generation procedure

Push button parliament–why India needs a non-partisan, recorded vote system

Decisions of national importance are made by Parliamentary voting. Yet Indian Members of Parliament (MPs) vote with a remarkable lack of freedom and accountability. The introduction of the Tenth Schedule in the Constitution has crippled free expression, since it provides that MPs voting against ‘any direction’ of their Party are liable to disqualification from the legislature  In addition, except for Constitutional amendments, Indian Parliamentary Procedure Rules do not require votes of MPs to be recorded unless the Speaker’s decision is contested in the House. The result is that voting in the House has become mechanical, controlled by Party politics and devoid of responsibility. This paper comments on a general theory of democratic accountability through the lens of Parliamentary voting. It suggests that the voting system adopted in the Parliament is an effective indicator to measure the level of accountability of its Members. In the context of India, this paper argues that the level of accountability will increase to a desirable extent only when there is adoption of a recorded system for every important House vote. Upon examination of India’s record thus far (through the sample of the 14th Lok Sabha) it becomes evident that the level of divisions (recorded votes) is substantially lower than other countries. This leads the paper to probe, as to why that might be the case. Part II of the paper answers that question by examining the Tenth Schedule of the Constitution. The paper scrutinizes the disproportionate influence of the Party in decision making in the Parliament. Apart from dealing with the inherent problem of the Tenth Schedule, this paper suggests two procedural changes to make parliamentary expression more meaningful. Firstly, the recording of all important votes within the Parliament and secondly, registering Party whips with the Minister of Parliamentary Affairs so that the voter knows the clear stand of every Parliamentary continuum. The focus of the paper is thus to bring back the attention of the legislators to their central function, which is deliberation on and the passage of legislation.

Harnessing the ancestors: mutuality, uncertainty and ritual practice in the Eastern Cape Province, South Africa

In the Eastern Cape Province of South Africa, chronic economic uncertainty has seen social relations stretched to breaking point. Informants speak of a 'war between men and women'. While grinding poverty, death in the shape of the 'axe' (HIV/AIDS) and suspicion stalk the land, and the project of building the umzi (homestead) falters, hope for the future and with it, trust between people, leaches away. One response to such uncertainty is a turn to ritual. Through a nearly relentless schedule of ritual activity which invokes the ancestors and the Christian deity in various forms, Xhosa people attempt to dam up trust, secure ongoing investment in the rural homestead and sustain ties of reciprocity both among rural people and between them and their urban kin. It is also through the staging of these rituals that women, acting together and in support of each other, are increasingly assertive – often in the face of a violent, rearguard opposition from men - in their efforts to exercise agency over the differentiated, fragmented and fragile social and economic relationships within their homesteads and across their villages.

Subsídios para a gestão dos planos de aplicação de vinhaça (PAV): um estudo de caso da região de Piracicaba

Concomitantemente à produção de etanol, a partir da fermentação de diferentes matérias-primas (cana-de-açúcar, beterraba, milho, trigo, batata, mandioca), produz-se a vinhaça. A vinhaça da cana-de-açúcar é gerada na proporção média de 12 litros para cada litro de etanol. O Brasil é o maior produtor mundial de cana-de-açúcar (570 milhões de toneladas, em 2009) com a produção de 27 bilhões de litros/ano de etanol, no ciclo 2009/2010, basicamente para fins carburantes, e, portanto, a quantidade de vinhaça produzida é da ordem de 320 bilhões de litros/ano. Dentre as possíveis soluções para a destinação da vinhaça, tais como: concentração, tratamento químico e biológico ou produção de biomassa, é sua aplicação no solo a forma mais usual de disposição. No entanto, sua aplicação no solo não pode ser excessiva nem indiscriminada, sob pena de comprometer o ambiente e a rentabilidade agrícola e industrial da unidade sucroalcooleira. A necessidade de medidas de controle sobre a aplicação de vinhaça no solo do Estado de São Paulo, que concentra a produção de 60% do etanol produzido no Brasil, levou à elaboração da Norma Técnica P4.231, em 2005. A constatação do cumprimento dos itens desta Norma é uma das ações do agente fiscalizador, no monitoramento da geração e destinação da vinhaça pelos empreendimentos produtores de etanol. Os itens 5.7.1 e 5.7.2, desta Norma, tornam obrigatório o encaminhamento à CETESB (Companhia Ambiental do Estado de São Paulo), para fins de acompanhamento e fiscalização, até o dia 02 de abril de cada ano, o PAV (Plano de Aplicação de Vinhaça). Com o intuito de proporcionar melhor entendimento da Norma P4.231, contribuir para otimização de sua aplicabilidade e melhoria e perceber a realidade prática da aplicação da vinhaça, foram analisados PAVs protocolados na Agência Ambiental de Piracicaba, licenças concedidas, processos de licenciamento e realizadas vistorias a campo. Conclui-se que a Norma P4.231 representa um avanço no gerenciamento do uso da vinhaça no Estado de São Paulo, por disciplinar a disposição de vinhaça no solo, tornando obrigatórios: demarcações de áreas protegidas e núcleos populacionais, caracterização de solo e da vinhaça, doses máximas a serem aplicadas, estudos da geologia e hidrogeologia locais, monitoramento das águas subterrâneas, impermeabilização de tanques e dutos. Estabelece critérios a serem obedecidos por lei, e todos são condutas de boas práticas de proteção ao meio, que repercutem em maior rentabilidade agrícola e industrial. A Norma P4.231 é bem elaborada, complexa e extensa, o que a torna de difícil execução. Para facilitar sua aplicabilidade, sugere-se o estabelecimento de um cronograma de prioridades: impermeabilização dos tanques e dutos, drenos testemunha com funcionamento otimizado e boa caracterização do que está sendo aplicado, se vinhaça pura ou se misturada a águas residuárias. Das oito empresas deste estudo, apenas quatro (as maiores) vêm protocolando os PAVs com regularidade, desde 2005. As informações apresentadas foram incompletas e, em alguns casos, precárias. Mesmo com lacunas, os dados fornecidos, desde o início da obrigatoriedade do PAV, foram de utilidade para esboçar o perfil da atividade sucroalcooleira na região estudada.

Estudo representacional da participação familiar nas atividades dos centros de atenção psicossocial no município de Natal-RN

Comprehending social representations of users relatives of Psychosocial Care Centers (CAPS) from Natal-RN, about their participation in the activities of these services, was the purpose of this study. The research instrument used was a semi-structured interview, led to 28 relatives of users of East and West CAPS II, East and North CAPS-ad, involved in the Relative Therapeutic Group, in Relative Meeting, in the Assembly of Users, Technicians and Relatives, according to the therapeutic schedule of each health services, between August to November 2007. Data obtained in family and users identification were characterized with the aid of charts and boards in absolute and/or percentage values. The discursive material from the guide from interviews was submitted to the informational resource ALCESTE (Analyse Lexicale par Contexte d'un Ensemble of Segments of Texte), and analyzed on the basis of the Theory of Social Representations and Central Nucleus Theory. Most of the relatives were women, married, aged over 50 years, who participated for more than two years in CAPS activities, and a coexistence of more than 11 years with the user. From the classification system of ALCESTE were selected categories, identified by: Category 1, Treatment Improvements and Expectations; Category 2, Living User Before and After; Category 3, Activities Relevance, Contradictions and Suggestions; Category 4, Guidelines -- Psychopharmacology and Medicalization; Category 5, Family Participation and Activities; and Category 6, Therapeutic Conditions Thanks, Tips and Vulnerability. The social representation of the family exists in the desire for change, identifying that we need to promote change by the continuity of therapeutic activities and overcome the detected inconsistencies, targeted by strengthening and by the stability of improvements in living and health conditions of users, experienced in CAPS treatment. The central nucleus had corresponded to positive changes in health and living conditions of users, and the peripheral elements were constituted by family conducts before and during treatment, and the expectations of changes in activities, especially in workshops. Despite this family participation be considered important, it still does not meet conditions to promote the inclusion of family, under an emancipating point of view, capable of causing in subject the hope for autonomy, initiative, individual and collective growths, a closer and active involvement in therapeutic activities, in workshops and discussions

O sertão potiguar comunica: midiatização e práticas sociais. Ou como a recepção da pauta política se desdobra em práticas sociais em Pau dos Ferros

This dissertation is the result of the development of a two-year research entitled POTIGUAR ACROSS THE COMMUNICATION: MEDIATIZATION AND SOCIAL PRACTICES. Or as the reception of the political agenda unfolds in social practices of the Pau dos Ferros, showwing Pau dos Ferros as a provincial oestano of Rio Grande do Norte, now living a meaningful set of social transformations, which interact with practices media that have just mediatized new public policies in the area of Technical Education and Higher Education. Thus, with the introduction and expansion of state and federal public policy of democratization of Technical and Higher Education in the period 2002 to 2010, the phenomenon of migration of students from elementary and high school, before existing in the region has changed significantly in that Pau dos Ferros polo is made. The concentration of the media city in the hands of politicians, in their favor, and the emergence of new midiatizações are contributed to the formation of this (non-migration) and other social practices, reinventing and rearranging the schedule of the ideas and concepts about the educational practices. Our goal is to observe the relationship of interaction between media, politics and education and examine how young students are realizing this interaction. Under the prospects of receiving the light of Cultural Studies, strolling our research primarily on the technique of focus group data collection

Peso adulto de matrizes em rebanhos de seleção da raça Nelore no Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Tariffs and the Plano Real in Brazil

Includes bibliography

Ipsis video litteris: processos e procedimentos artísticos da escrita na televisão - videografia

Pós-graduação em Artes - IA

Interatividade na TV digital universitária: programa debate livre

Pós-graduação em Televisão Digital: Informação e Conhecimento - FAAC

Taxas e intervalos de alimentação na produção de Tilápia em tanque-rede com dispensador automático de ração

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Adubação foliar de sulfato de zinco na produtividade e teores foliares de zinco e fosforo de cafeeiros arábica

Aiming to evaluate the dose and application schedule of foliar Zn-sulfate spraying in growing and yield of Arabic coffee Mundo Novo, a field experiment was set up on Distroferric Red Latosol, at the Experimental Station of the EPAMIG in São Sebastião do Paraíso. The statistical design used was randomized blocks in s 4 x 2 factorial scheme with five replications and a 30-plant plot with six central valid or four applications per agricultural year. Phosphorus and zinc leaf levels were evaluated for eight years and the yields. It was possible to conclude that there is a positive response to the in the leaves. Four low concentrations sprayings promoted higher yields than two high concentrations. The highest yields were achieved with 10.8 and 12.6 kg ha-1 of ZnSO4 and 4 yearly applications, respectively. It is suggested as a critical range for the Zn leaves values between 10 and 28 mg kg-1 and for P/Zn ratio, between 100 and 150. ) was sprayed under 4 concentrations 0; 0.5; 1.0 and 1.5%, two applied on the leaves in terms of yield, and to Zn levels