31 resultados para Regulação gênica

em Universidade Federal do Rio Grande do Norte(UFRN)


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A Constituição Federal de 1988 e o Estatuto da Cidade estabelecem o Plano Diretor como instrumento básico da política de ordenamento territorial, tendo como princípio fundamental o cumprimento da função social da propriedade e do direito à cidade. Na perspectiva de adequação às diretrizes e objetivos da política urbana estabelecidos em 1988, o município de Natal elaborou os Planos Diretores de 1994 e 2007, definindo instrumentos e parâmetros de regulação do uso e ocupação do solo possíveis de assegurar o cumprimento da função social da propriedade urbana e de gerar subsídios ao planejamento e à gestão da cidade. Apesar de Natal ter sido um dos municípios brasileiros pioneiros na adoção desses princ pios, antecipando e incorporando os instrumentos que em 2001 viriam a ser definidos no Estatuto da Cidade, identifica-se que alguns desses instrumentos e parâmetros direcionados à regulação do uso e ocupação do solo não tiveram sua aplicação plena, a exemplo do mecanismo de acompanhamento e controle dado pelo Estoque de Área Edificável e da Densidade, que foi substituída pelo Coeficiente de Aproveitamento no Plano Diretor de 2007. Questionando esse procedimento, busca-se na presente pesquisa investigar de que maneira essa substituição do parâmetro densidade pelo coeficiente de aproveitamento influenciou na capacidade da gestão pública de regular os processos de uso e ocupação do solo, de forma a adequar a sua intensificação ao suporte da infraestrutura instalada. Foram tomadas como referência teórico-conceitual as contribuições sobre a prática de planejamento urbano no Brasil, nos marcos do ideário da reforma urbana, com destaque para as reflexõe s de Flávio Villaça, Orlando Alves Santos Junior e Daniel Todtmann Montandon, Luiz César de Q. Ribeiro, Raquel Rolnik, Ermínia Maricato, Laura Machado de Bueno e Renato Cymbalista, José Roberto Bassul e Carlos F. Lago Burnett, e, com relação aos parâmetros de controle urbanístico, o estudo identifica as diferentes abordagens sobre a densidade urbana e o coeficiente de aproveitamento com base nas reflexões de Claudio Acioly Jr., Forbes Davidson, Juan Luis Mascaró, Ricardo Ojima, Marcelo de Souza, José Rámon Navarro Vera e Armando Ortuño Padilla, Nestor Goulart Reis, Marta Dora Grostein e Susana Ricardo Alves. Como conclusão, discute-se a hipótese formulada, inicialmente, de que a mudança de parâmetros verificada colocou limites para o município realizar uma gestão adequada do solo urbano e, portanto, de fazer cumprir a função social da propriedade, considerando a necessidade de adequação entre a intensificação do uso e ocupação do solo e a infraestrutura instalada

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studies using UV as a source of DNA damage. However, even though unrepaired UV-induced DNA damages are related to mutagenesis, cell death and tumorigenesis, they do not explain phenotypes such as neurodegeneration and internal tumors observed in patients with syndromes like Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS) that are associated with NER deficiency. Recent evidences point to a role of NER in the repair of 8-oxodG, a typical substrate of Base Excision Repair (BER). Since deficiencies in BER result in genomic instability, neurodegenerative diseases and cancer, it was investigated in this research the impact of XPC deficiency on BER functions in human cells. It was analyzed both the expression and the cellular localization of APE1, OGG1 e PARP-1, the mainly BER enzymes, in different NER-deficient human fibroblasts. The endogenous levels of these enzymes are reduced in XPC deficient cells. Surprisingly, XP-C fibroblasts were more resistant to oxidative agents than the other NER deficient fibroblasts, despite presenting the highest of 8-oxodG. Furthermore, subtle changes in the nuclear and mitochondrial localization of APE1 were detected in XP-C fibroblasts. To confirm the impact of XPC deficiency in the regulation of APE1 and OGG1 expression and activity, we constructed a XPC-complemented cell line. Although the XPC complementation was only partial, we found that XPC-complemented cells presented increased levels of OGG1 than XPC-deficient cells. The extracts from XPC-complemented cells also presented an elevated OGG1 enzimatic activity. However, it was not observed changes in APE1 expression and activity in the XPCcomplemented cells. In addition, we found that full-length APE1 (37 kDa) and OGG1- α are in the mitochondria of XPC-deficient fibroblasts and XPC-complemented fibroblasts before and after induction of oxidative stress. On the other hand, the expression of APE1 and PARP-1 are not altered in brain and liver of XPC knockout mice. However, XPC deficiency changed the APE1 localization in hypoccampus and hypothalamus. We also observed a physical interaction between XPC and APE1 proteins in human cells. In conclusion, the data suggest that XPC protein has a role in the regulation of OGG1 expression and activity in human cells and is involved mainly in the regulation of APE1 localization in mice. Aditionally, the response of NER deficient cells under oxidative stress may not be only associated to the NER deficiency per se, but it may include the new functions of NER enzymes in regulation of expression and cell localization of BER proteins

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The mobilization of food reserves in storage tissues and allocation of their hydrolysis products in the growing axis are critical processes for the establishment of seedlings after germination. Therefore, it is crucial for mobilization of reserves to be synchronized with the growing axis, so that photosynthetic activity can be started before depletion of reserves. For this, integrative approaches involving different reserves, different hydrolysis products and interaction between storage and growing axis tissues, either through hormones or metabolites with signaling role, can contribute greatly to the elucidation of the regulation mechanisms for reserve mobilization. In this study, was hypothesized that hormones and metabolites have different actions on reserve mobilization, and there must be a crossed effect of sugars on the mobilization of proteins and amino acids on lipids and starch mobilization in sunflower seedlings. This study was conducted with seeds of sunflower (Helianthus annuus L.) hybrid Helio 253 using in vitro culture system. Seeds were germinated on Germitest® paper and grown on agar-water 4 g/L without addition of nutrients during 9 days after imbibition (DAI) for growth curve. To verify the effect of metabolites and hormones, seedlings were transferred in the 2nd DAI to agar-water 4 g/L supplemented with increasing concentrations of sucrose or L-glutamine, abscisic acid, gibberellic acid or indolebutyric acid. The results of this study confirm that the mobilization of lipids and storage proteins occurs in a coordinated manner during post-germination growth in sunflower, corroborating the hypothesis that the application of external carbon (sucrose) and nitrogen (L-glutamine) sources can delay the mobilization of these reserves in a crossed way. Moreover, considering the changes in the patterns of reserve mobilization and partition of their products in seedlings treated with different growth regulators, it is evident that the effects of metabolites and hormones must involve, at least in part, distinct mechanisms of action

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Sugarcane has an importance in Brazil due to sugar and biofuel production. Considering this aspect, there is basic research being done in order to understand its physiology to improve production. The aim of this research is the Base Excision Repair pathway, in special the enzyme MUTM DNA-glycosylase (formamidopyrimidine) which recognizes oxidized guanine in DNA. The sugarcane scMUTM genes were analyzed using four BACs (Bacterial Artificial Chromosome) from a sugarcane genomic library from R570 cultivar. The resulted showed the presence in the region that had homology to scMUTM the presence of transposable elements. Comparing the similarity, it was observed a highest similarity to Sorghum bicolor sequence, both nucleotide and peptide sequences. Furthermore, promoter regions from MUTM genes in some grass showed different cis-regulatory elements, among which, most were related to oxidative stress, suggesting a gene regulation by oxidative stress

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Gene therapy is one of the major challenges of the post-genomic research and it is based on the transfer of genetic material into a cell, tissue or organ in order to cure or improve the patient s clinical status. In general, gene therapy consists in the insertion of functional genes aiming substitute, complement or inhibit defective genes. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, a key issue is to create systems, vectors, able to transfer and protect the DNA until it reaches the target. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easy to produce, present suitable stability and enable transfection. The aim of this work was to evaluate two different non-viral vectors, cationic liposomes and nanoemulsions, and the possibility of their use in gene therapy. For the two systems, cationic lipids and helper lipids were used. Nanoemulsions were prepared using sonication method and were composed of Captex® 355; Tween® 80; Spam® 80; cationic lipid, Stearylamine (SA) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and water (Milli-Q®). These systems were characterized by average droplet size, Polidispersion Index (PI) and Zeta Potential. The stability of the systems; as well as the DNA compaction capacity; their cytotoxicity and the cytotoxicity of the isolated components; and their transfection capacity; were also evaluated. Liposomes were made by hydration film method and were composed of DOTAP; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), containing or not Rhodaminephosphatidylethanolamine (PE- Rhodamine) and the conjugate Hyaluronic Acid DOPE (HA-DOPE). These systems were also characterized as nanoemulsions. Stability of the systems and the influence of time, size of plasmid and presence or absence of endotoxin in the formation of lipoplexes were also analyzed. Besides, the ophthalmic biodistribution of PE-Rhodamine containing liposomes was studied after intravitreal injection. The obtained results show that these systems are promising non-viral vector for further utilization in gene therapy and that this field seems to be very important in the clinical practice in this century. However, from the possibility to the practice, there is still a long way

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The aim of this study was to determine the effects of the use of rosuvastatin in patients with atherosclerosis, in relation to blood parameters of selenium and selenoproteins, and also observe possible changes in gene expression of selenoproteins in these patients. The sample consisted of 27 adult and elderly patients with a clinical diagnosis of coronary artery disease undergoing angioplasty, treated at Natal Hospital Center hospital, Natal, RN. Patients were treated with rosuvastatin 10 mg/day during four months. Anthropometric variables such as body mass index (BMI) and Waist circumference (WC) were measured before and after treatment, as well as lipid profile, blood glucose and liver enzymes (AST and ALT). The diet of the patients was also analyzed using 24-hour diet recall. We analyzed the concentrations of selenium in plasma and erythrocytes, and also the activity of Glutathione Peroxidase and gene expression by Real Time PCR of selenoproteins GPx1, SelP1 and SelN1. Patients had mean age of 61.0 ± 9.4 years, 59.3% were men and 40.7% were women. After four months of treatment there was significant reduction of CA and, according to BMI, most were overweight. The intake of macronutrients, cholesterol, polyunsaturated fatty acids, monounsaturated and saturated was adequate, but the energy and fiber intake was below the recommendations. Regarding the selenium intake was observed a high prevalence of inadequacy. As expected, after treatment with rosuvastatin, a significant reduction in total cholesterol, LDL and glucose, which was not observed for HDL. Selenium concentrations in plasma and erythrocytes showed no changes, keeping within the established cutoffs. We observed a significant increase in GPx enzyme activity and mRNA expression of GPX1 and SEPN1, but not for gene SEPP1. Thus, it was found that treatment with rosuvastatin did not reduce the expression of selenoproteins. More studies are needed to clarify the effects of rosuvastatin on gene expression of selenoproteins in patients with atherosclerosis

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The study had as objective to evaluate the zinc status by means of dietary intake, zinc in plasma and in erythrocytes and the metallothionein gene expression in patients with atherosclerosis in use of rosuvastatin. The research involved 27 adult and elderly patients of both genders with atherosclerosis that were treated with rosuvastatin (10mg/day) during 4 months. We performed the dosage of lipids, glucose, AST and ALT, ultrasensitive C-reactive protein (hsCRP), plasmatic and erythrocyte zinc and 1 and 2 metallothionein gene expression. The assessment of body mass index (BMI) and abdominal circumference (AC) was performed, besides the analysis of dietary intake of patients. The majority of the evaluated patients presented overweight, before and after the treatment, with no significant difference between the times of the study. It was identified that the AC was significantly reduced in the group (p<0.05) after the intervention. The majority of the patients had intake below the recommendation of calories and fibers and above recommendation of proteins. The mono and polyunsaturated fats were adequate for the majority of the patients, however, the saturated fat and cholesterol were consumed in excess by a great part of the individuals. The intake of zinc was inadequate, being noticed an inadequacy of 100% in the male gender and of 84% in the female. After the treatment with rosuvastatin there was a significant reduction in the total cholesterol (TC) and LDL-c (p<0.01) and no alterations were observed in the HDL-c and triacylglycerols. It was also verified that the reduction of glycemia (p<0.05) and of hsCRP (p<0.01). The analysis did not demonstrate significant differences in the plasmatic and erythrocyte zinc concentration after the treatment. There was, after the treatment, reduction of the MT1F gene (p<0.05) without, however, occurring significant alterations in the MT2A gene. The treatment with rosuvastatin was effective in the reduction of TC and LDL-c, and promoted the reduction of inflammatory marker hsCRP. The zinc in the plasma and erythrocyte was not altered by the use of the medication and there was a reduction in the MT1F gene, possibly due to the reduction of inflammation. The majority of patients presented inadequate intake of zinc and this inadequacy did not have relation with the mineral parameters in plasma and erythrocytes or with the metallothionein gene expression

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Studies report that the pathophysiological mechanism of diabetes complications is associated with increased production of Reactive Oxygen Species (ROS)-induced by hyperglycemia and changes in the capacity the antioxidant defense system. In this sense, the aim of this study was to evaluate changes in the capacity of antioxidant defense system, by evaluating antioxidant status, gene expression and polymorphisms in the genes of GPx1, SOD1 and SOD2 in children, adolescents and young adults with type 1 diabetes. We studied 101 individuals with type 1 diabetes (T1D) and 106 normoglycemic individuals (NG) aged between 6 and 20 years. Individuals with type 1 diabetes were evaluated as a whole group and subdivided according to glycemic control in DM1G good glycemic control and DM1P poor glycemic control. Glycemic and metabolic control was evaluate by serum glucose, glycated hemoglobin, triglycerides, total cholesterol and fractions (HDL and LDL). Renal function was assessed by measurement of serum urea and creatinine and albumin-to-creatinine ratio (ACR) in spot urine. Antioxidant status was evaluate by content of reduced glutathione (GSH) in whole blood and the activity of erythrocyte enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). We also analyzed gene expression and gene polymorphisms of GPx1 (rs1050450), SOD1 (rs17881135) and SOD2 (rs4880) by the technique of real-time PCR (Taqman®). Most individuals with DM1 (70.3%) had poor glycemic control (glycated hemoglobin> 8%). Regarding the lipid profile, individuals with type 1 diabetes had significantly elevated total cholesterol (p <0.001) and LDL (p <0.000) compared to NG; for triglycerides only DM1NC group showed significant increase compared to NG. There was an increase in serum urea and RAC of individuals with DM1 compared to NG. Nine individuals with type 1 diabetes showed microalbuminuria (ACR> 30 mg / mg). There was a decrease in GSH content (p = 0.006) and increased erythrocyte GPx activity (p <0.001) and SOD (p <0.001) in DM1 group compared to NG. There was no significant difference in the expression of GPx1 (p = 0.305), SOD1 (.365) and SOD2 (0.385) between NG and DM1. The allele and genotype frequencies of the polymorphisms studied showed no statistically significant difference between the groups DM1 and NG. However, the GPx1 polymorphism showed the influence of erythrocyte enzyme activity. There was a decrease in GPx activity in individuals with type 1 diabetes who had a polymorphic variant T (p = 0.012). DM1 patients with the polymorphic variant G (AG + GG) for polymorphism of SOD2 (rs4880) showed an increase in the RAC (p <0.05). The combined data suggest that glucose control seems to be the predominant factor for the emergence of changes in lipid profile, renal function and antioxidant system, but the presence of the polymorphisms studied may partly contribute to the onset of complications

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The gas retail represents the end of a section of the oil and natural gas derivative chain, for it is at this stage where the commercialization of those merchandises takes place towards the costumers. This process involves an enormous amount of economic agents, which reflects on an activity of great influence on the citizen's everyday. By the time of the gas retail price liberalization, in 2002, there were great expectations towards that measure, for the insertion of that segment in a competitive market was likely to create a decrease in prices. As there was not a drastic drop off in cost, the question was no longer the price itself, but, predominantly, the conduct taken by the economic agents that operate the market. Not in vain, the segment introduces a greater number of different procedures combined with the organs that compose the Brazilian System of Competition Protection. What is understood, however, is that many of these complaints are made in a lightly way, without a proper analysis of the market and its practices, that being why, in this paper, evidences the causes of these complaints and explained what, in fact, occurs in this market. Also, the organs that protect the free initiative in the sector use different methods to assess anticompetitive practices, which are counterproductive on the combat of anticompetitive practice, that being why the present paper analyzes the used methods on a critic perspective, choosing one which is believed to be the most adequate. The present work also tries to present the gas retail prices on a constitutional, free competition, free initiative and consumers defense perspective, analyzing the competition s aspects on the gas market; the shaping of the gas prices; the market boundaries; the anti-competitive practices under the gas market; and analyze the possibility, according to the defined economic standards in the constitutional text of existing a greater control or gas price indexing and/or regulation which limits the distributors and resellers profit on gas. Still, in consequence of this analysis, a study on Natal s market behavior will be developed in its competitive feature. That being said, moreover being a theoretical-descriptive study, data and statistics gathered is used, which will lead, willing to grasp an experiential study on a few aspects of the Potiguar gas retail market

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This work presents an analysis about the legitimation of independent regulatory commission`s rulemaking power by participation procedure. It is observed that political and administrative decentralization and fragmentation of State, with the purpose of approaching citizens and provide, more efficiently, the functions acquired by the passage of the Welfare State, leads to a deficit of legitimacy (democratic crisis), which is noticeable in the making of legal norms by directors of independent regulatory commission to regulate specific economic sector. However, we understand that this crisis stems from the observation of the contemporary world from dogmas and legal institutions of the eighteenth century, without their evolution and adaptation to the modern world. The legitimacy must be perceived as the justification of power, relation command /obedience, which, from the Modern State, has the democracy as standard. Therefore, just as the world has evolved and demanded political and administrative decentralization to accompany him, it is necessary to the development of the idea of representative democracy (formal legitimacy) to participatory democracy (legitimacy stuff). Legitimacy is not confused with the legality: as the legality is on observance to internal legal system, the "rules of play"; legitimacy, as inputs to be fed into this system, the selection of the different expectations in the environment. Nevertheless, the legitimacy will take place by legality, through introduction of rational and communicative procedures: procedures get fundamental importance because these will be the means to select the expectations to be introduced in the legal system in order to make decisions more fair, rational and qualified towards society. Thus, it is necessary to its opening to the environment for dialogue with the government. In this context, we try to make an analysis of constitutional norms based on systematic and teleological interpretation of these norms to build these arguments. According to the Constitution of 1988, participatory democracy is a result of the democratic principle (sole paragraph of art. 1 of the Constitution), and it is an expression of citizenship and political pluralism, both foundations of Republic (respectively Art. 1st, inc . V and II of the Constitution), as well as the national consciousness. From another point of view, that principle consists of an evolution in the management public affairs (principle of Republic). The right of interested participate in the rulemaking process derives both the principle of popular participation (part of the democratic principle) and the republican principle as the due process constitutional (art. 5, LIV and LV, CF/88) and the right to petition (Art . 5 °, inc. XXXIV, "a", CF/88), and it is the duty of the State not only be open to participation and encourage it. Ignoring stakeholder involvement in procedures and / or expressions compiled can be causes of invalidation of the rule of law produced by addiction of procedure, motive, motivation and/or because of the administrative act. Finally, we conclude that the involvement of stakeholders in the process of making rules within the independent regulatory commission is the legitimacy and the validity of rules; and that, despite of the expressions do not bind the decision making, they will enter the system as juridical fact, balancing the field of technical discretionary of agencies

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In the middle of modern social changes produced by globalization and capitalism, several markets have changed. States have left the direct coordination of these markets (chiefly public utility sector in the form of monopolies), introducing regulation in order to promote competition. These changes have affected natural gas industry by promoting competition as a key factor to the development and the increase of firms in this market. The regulatory reform of natural gas industry ocurred in EUA and Europe Union and it has produced its first results. In Brazilian context, Constitutional Amendment nbr. 09 and Federal Law nbr. 9.478/97 ( Petroleum Law ) opened the natural gas market to a broad range of private economic agents and they finished the monopoly over the industry before managed by Petrobras. The new regulatory framework of Brazilian natural gas industry has designed competition as a central element to the new form of managment of business and contractual relationships of this industry. Among the regulatory instruments, open access regulation in natural gas pipelines is directed to promote competition. The questions arised about its implementation in Brazilian context are studied in the present work, in which it is discussed the constitutional rules and principles are to be applied to the open access regulation within the theme of statal regulation of economy present in constitutional economic order

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Conselho Nacional de Desenvolvimento Científico e Tecnológico

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Broadly speaking, the concept of gene therapy involves the transfer of a genetic material into a cell, tissue, or organ in order to cure a disease or at least improve the clinical status of a patient. Making it simple, gene therapy consists in the insertion of functional genes into cells containing defective genes by substituting, complementing or inhibiting them. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, it is a key issue to create systems able to transfer and protect the DNA until it reaches the target, the vectors. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easily produced, present controllable stability and enable transfection. The aim of this work was to develop an emulsion for gene therapy and evaluate its ability to compact nucleic acids by the development of a complex with the plasmid pIRES2-EGFP. The first step was to determine the Hydrophilic Lipophilic Balance (HLB) of the Captex® 355 (oily internal phase of the emulsion) through long and short term stability assays. Based on the results, emulsions composed of Captex® 355, Tween 20® and Span 60® with 10.7 HLB were produced by three different methods: phase inversion, spontaneous emulsification and sonication. The results showed that the lowest diameter and best stability of the emulsions were achieved by the sonication method. The cationic emulsions were made by adding DOTAP to the basic emulsion. Its association with pIRES2-EGFP was evaluated by electrophoresis. Several rates of emulsion and DNA were evaluated and the results showed that 100% of the complex was formed when the rate DOTAP/DNA(nmol/µg) was 130. In conclusion, the overall results show the ability of the proposed emulsion to compact pIRES2-EGFP, which is a requirement to a successful transfection. Therefore, such formulation may be considered a promising candidate for gene therapy

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The use of clustering methods for the discovery of cancer subtypes has drawn a great deal of attention in the scientific community. While bioinformaticians have proposed new clustering methods that take advantage of characteristics of the gene expression data, the medical community has a preference for using classic clustering methods. There have been no studies thus far performing a large-scale evaluation of different clustering methods in this context. This work presents the first large-scale analysis of seven different clustering methods and four proximity measures for the analysis of 35 cancer gene expression data sets. Results reveal that the finite mixture of Gaussians, followed closely by k-means, exhibited the best performance in terms of recovering the true structure of the data sets. These methods also exhibited, on average, the smallest difference between the actual number of classes in the data sets and the best number of clusters as indicated by our validation criteria. Furthermore, hierarchical methods, which have been widely used by the medical community, exhibited a poorer recovery performance than that of the other methods evaluated. Moreover, as a stable basis for the assessment and comparison of different clustering methods for cancer gene expression data, this study provides a common group of data sets (benchmark data sets) to be shared among researchers and used for comparisons with new methods

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The main goal of this work is to investigate the suitability of applying cluster ensemble techniques (ensembles or committees) to gene expression data. More specifically, we will develop experiments with three diferent cluster ensembles methods, which have been used in many works in literature: coassociation matrix, relabeling and voting, and ensembles based on graph partitioning. The inputs for these methods will be the partitions generated by three clustering algorithms, representing diferent paradigms: kmeans, ExpectationMaximization (EM), and hierarchical method with average linkage. These algorithms have been widely applied to gene expression data. In general, the results obtained with our experiments indicate that the cluster ensemble methods present a better performance when compared to the individual techniques. This happens mainly for the heterogeneous ensembles, that is, ensembles built with base partitions generated with diferent clustering algorithms