Model-based clustering in gene expression microarrays: An application to breast cancer data

In microarray studies, the application of clustering techniques is often used to derive meaningful insights into the data. In the past, hierarchical methods have been the primary clustering tool employed to perform this task. The hierarchical algorithms have been mainly applied heuristically to these cluster analysis problems. Further, a major limitation of these methods is their inability to determine the number of clusters. Thus there is a need for a model-based approach to these. clustering problems. To this end, McLachlan et al. [7] developed a mixture model-based algorithm (EMMIX-GENE) for the clustering of tissue samples. To further investigate the EMMIX-GENE procedure as a model-based -approach, we present a case study involving the application of EMMIX-GENE to the breast cancer data as studied recently in van 't Veer et al. [10]. Our analysis considers the problem of clustering the tissue samples on the basis of the genes which is a non-standard problem because the number of genes greatly exceed the number of tissue samples. We demonstrate how EMMIX-GENE can be useful in reducing the initial set of genes down to a more computationally manageable size. The results from this analysis also emphasise the difficulty associated with the task of separating two tissue groups on the basis of a particular subset of genes. These results also shed light on why supervised methods have such a high misallocation error rate for the breast cancer data.

Zygosity Diagnosis in the Absence of Genotypic Data: An Approach Using Latent Class Analysis

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

Systematic characterization of mutations in yeast acetohydroxyacid synthase: Interpretation of herbicide-resistance data

Acetohydroxyacid synthase (AHAS, EC 4.1.3.18) catalyses the first step in branched-chain amino acid biosynthesis and is the target for sulfonylurea and imidazolinone herbicides, which act as potent and specific inhibitors. Mutants of the enzyme have been identified that are resistant to particular herbicides. However, the selectivity of these mutants towards various sulfonylureas and imidazolinones has not been determined systematically. Now that the structure of the yeast enzyme is known, both in the absence and presence of a bound herbicide, a detailed understanding of the molecular interactions between the enzyme and its inhibitors becomes possible. Here we construct 10 active mutants of yeast AHAS, purify the enzymes and determine their sensitivity to six sulfonylureas and three imidazolinones. An additional three active mutants were constructed with a view to increasing imidazolinone sensitivity. These three variants were purified and tested for their sensitivity to the imidazolinones only. Substantial differences are observed in the sensitivity of the 13 mutants to the various inhibitors and these differences are interpreted in terms of the structure of the herbicide-binding site on the enzyme.

Life transitions and changing physical activity patterns in young women

Background: Physical activity (PA) patterns are likely to change in young adulthood in line with changes in lifestyle that occur in the transition from adolescence to adulthood. The aim of this study was to ascertain whether key life events experienced by young women in their early twenties are associated with increasing levels of inactivity. Methods: This was a 4-year follow-up of 7281 participants (aged 18 to 23 years at baseline) in the Australian Longitudinal Study of Women's Health, with self-reported measures of PA, life events, body mass index (BMI), and sociodemographic variables. Results: The cross-sectional data indicated no change in PA between baseline (57% active) and follow-up (56% active). However, for almost 40% of the sample, PA category changed between baseline and follow-up, with approximately 20% of the women changing from being active to inactive, and another 20% changing from being inactive to active. After adjustment for age, other sociodemographic variables, BMI, and PA at baseline, women who reported getting married, having a first or subsequent child, or beginning paid work were more likely to be inactive at follow-up than those who did not report these events. Conclusions: The results suggest that life events such as getting married, having children, and starting work are associated with decreased levels of PA in young adult women. Strategies are needed to promote maintenance of activity at the time when most women experience these key life-stage transitions.

The developmental activities of elite ice hockey players

The purpose of this study was to analyze the development of four 20 year-old elite hockey players through an in-depth examination of their sporting activities. The theoretical framework of deliberate practice (Ericsson, Krampe, & Tesch-Römer, 1993) and the notion of deliberate play (Côté, 1999) served as the theoretical foundations. Interviews were conducted to provide a longitudinal and detailed account of each participant's involvement in various sporting activities. The interviewer asked questions about the conditions and sporting activities for each year of development. The data obtained were validated through independent interviews conducted with three parents of three different athletes. The results were consistent with Côté's (1999) three stages of development in sport: the sampling (age 6-12), specializing (age 13-15), and investment (age 16+) years.

Relationship of ventricular longitudinal function to contractile reserve in patients with mitral regurgitation

Background Latent left ventricular (LV) dysfunction in patients with valvular or myocardial disease may be identified by loss of contractile reserve (CR) at exercise echocardiography. Contraction in the LV longitudinal axis may be more sensitive than radial contraction to minor disturbances of LV function. We sought to determine whether tissue Doppler measurement of longitudinal function could be used to identify CR. Methods Exercise echocardiography was performed in 86 patients (20 women, age 53 +/- 18 years), 72 with asymptomatic or minimally symptomatic mitral regurgitation, and 14 normal controls. Pulsed-wave tissue Doppler imaging (DTI) was used to measure maximum annular systolic velocity at rest and stress. Inducible ischemia was excluded by analysis of wall motion by an experienced observer. CR was defined by greater than or equal to5% improvement of stress compared with rest ejection fraction (EF). Exercise capacity was assessed from expired gas analysis. Results CR was present in 34 patients with mitral regurgitation (47%); peak EF in patients with and without CR was 74% +/- 11% versus 54% +/- 15% (P

In search of the ultimate ionosonde deduced equator

A further progress has been made in defining the ionosonde deduced equator (IDE) which characterises a latitudinal transition from the northern to southern hemisphere. It is now possible to define the global IDE location as the locus of the average position between geographic and geomagnetic equators. A more complete insight to the phenomenon of the third equator (i.e. after geographic and geomagnetic equators) was made possible due to availability of ionospheric height (h'F) data from three stations positioned close to the IDE in the American and the far-east sectors. The IDE ionospheric signature (or E-type signature), detected at these stations, consists of bi-annual h'F height increases. This signature however is not consistently observed during solar cycle and at times, particularly at sunspot minimum, a weak hemispheric signature is observed (i.e. the northern or southern hemisphere signature). In general, the height increase at the IDE are considerably smaller (by a factor of 4) than at other equatorial locations, indicating that the ionosphere at the IDE location becomes less disturbed. It is suggested that the equatorial longitudinal regions which can be associated with more consistent E-type signature are located in the central Pacific and at the east coast of America, close to the intersection points of the geographic and geomagnetic equators. (C) 2003 Elsevier Ltd. All rights reserved.

Data Mart para apoio ?? capacita????o em gest??o de pol??ticas p??blicas voltado para uma Escola de Administra????o P??blica

Este trabalho consiste num estudo de caso que se destina ao desenvolvimento de um Data Mart que possibilite a Escola Nacional de Administra????o P??blica ??? ENAP conhecer o perfil e o panorama geral da situa????o funcional dos servidores p??blicos federais que se capacitaram na Escola nos ??ltimos 7 anos. O aplicativo foi desenvolvido cruzando o banco de dados do sistema gerenciador dos cursos ministrados pela ENAP, onde est??o armazenadas informa????es sobre os alunos capacitados, os cursos realizados, os resultados alcan??ados, o perfil dos docentes e demais informa????es relativas ??s atividades da Escola, com os dados gerados pelo Sistema Integrado de Administra????o de Recursos Humanos ??? SIAPE, cuja extra????o de dados foi direcionada para os registros sobre a situa????o funcional, cargos, carreiras, fun????es, ??rg??os e alguns dados pessoais dos alunos, servidores p??blicos federais que se encontram registrados no SIAPE

Relationships and estimates of longitudinal growth stress in Eucalyptus dunnii at different ages

O objetivo desse trabalho foi obter estimativas da tensão de crescimento longitudinal em árvores vivas e verificar a sua relação com algumas características da madeira de Eucalyptus dunnii Maiden aos oito, treze, quinze e dezenove anos de idade. O material foi proveniente da Empresa Procopiak Compensados e Embalagens S.A., localizada no Município de Canoinhas, Santa Catarina. Os níveis de tensão longitudinal de crescimento foram mensurados indiretamente pelo método do "CIRAD-Forêt", na árvore viva, e estimados a partir do módulo de elasticidade dinâmico e do módulo de elasticidade obtido no ensaio de tração paralela à grã. A deformação residual longitudinal (DRL) e as estimativas das tensões de crescimento longitudinais apresentaram tendência de aumento, na média, com a idade do material. A DRL apresentou correlação, positiva e significativa, com todas as estimativas das tensões de crescimento longitudinais, sendo de maior magnitude aos 13, 15 e 19 anos de idade. A densidade básica apresentou maiores correlações, positivas e significativas, com o módulo de elasticidade dinâmico, estimado no sentido longitudinal, para a madeira na condição de saturação e a 12% de umidade, em todas as idades avaliadas. Todas as estimativas das tensões de crescimento longitudinais apresentam elevadas correlações, positivas e significativas, entre si.

Variação radial da retratibilidade e densidade básica da madeira de Eucalyptus saligna Sm.

A ultra-estrutura e a composição química da madeira, bem como suas propriedades físicas e mecânicas, variam significativamente entre espécies, entre árvores de uma mesma espécie e, mesmo, entre diferentes partes de uma mesma árvore. Com este trabalho objetivou-se o estudo dos parâmetros de retratibilidade e de densidade básica da madeira Eucalyptus saligna, com idade de 16 anos, proveniente de talhões experimentais da EMBRAPA Florestas, de Colombo, Paraná. As amostras foram retiradas à altura do DAP de quatro posições eqüidistantes a partir da medula em direção à periferia, correspondendo a 0, 33, 66 e 100%, com dimensões nominais de 1,0 x 2,0 x 3,0 cm, sendo a última dimensão no sentido longitudinal. Elas foram mantidas em câmara fechada com ventilação, próximo de soluções salinas supersaturadas, com o objetivo de proporcionar diferentes condições de umidade relativa. Uma vez atingidas as distintas condições de umidade de equilíbrio, as amostras foram secas em estufa a 105 ºC e obtidos os dados de retratibilidade e densidade básica da madeira nas posições mencionadas. Constataram-se valores de contração volumétrica mais baixos na região medular, apresentando um acréscimo para as demais posições. Comportamento semelhante foi observado para os coeficientes das contrações lineares nas direções tangencial e radial. O fator anisotrópico foi consideravelmente mais elevado na região medular, decrescendo substancialmente em direção ao alburno. A densidade básica não mostrou sinais efetivos de estabilidade, apesar de mostrar tendência de aumento em direção à periferia do tronco.

Avaliação das propriedades higroscópicas da madeira de Eucalyptus saligna Sm., em diferentes condições de umidade relativa do ar

O estudo da higroscopicidade é indispensável para o entendimento da trabalhabilidade, estabilidade dimensional, resistência mecânica e durabilidade natural da madeira. Neste trabalho objetivou-se a avaliação do teor de equilíbrio higroscópico para diversas condições de umidade relativa do ar, bem como da retratibilidade linear e volumétrica e da densidade básica da madeira de Eucalyptus saligna Sm. A madeira utilizada foi proveniente de árvores com 16 anos de idade, procedentes de talhões experimentais da EMBRAPA Florestas de Colombo, Paraná. Amostras com dimensões de 1,0x2,0x3,0 cm, sendo a última na direção longitudinal, foram colocadas em uma câmara fechada, sob ventilação, próximas de recipientes com soluções salinas supersaturadas, a fim de atingir determinada condição preestabelecida de teor de equilíbrio higroscópico. Após o equilíbrio da umidade da madeira nas distintas condições de umidade relativa, as amostras foram secas em estufa, para posterior avaliação. Os dados relativos à umidade de equilíbrio ajustaram-se muito bem às condições de umidade relativa adotadas neste estudo, tendo sido possível estimar com grande precisão o teor de equilíbrio higroscópico, para a faixa de aproximadamente 20 até 100% de umidade relativa. A madeira em estudo apresentou dados de retratibilidade bastante elevados, se comparados aos de outras da mesma faixa de densidade. Apesar dos elevados coeficientes de contração, o fator anisotrópico ou relação T/R mostrou-se próximo daquele encontrado na grande maioria das madeiras comerciais brasileiras. Verificaram-se ainda coeficientes de contrações mais suaves nos teores de umidade abaixo de 17%.