Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines

Background

Imatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.
Methods

We conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina Human WG-6 BeadChips were analyzed for each sample using SOLAR, whilst correcting for kinship structure.
Results

Cytotoxicity within cell lines was highly heritable following imatinib treatment (h2 = 0.60-0.73), but not omacetaxine treatment. Cell lines treated with an IC20 dose of imatinib or omacetaxine showed differential gene expression for 956 (1.96%) and 3,892 transcripts (7.97%), respectively; 395 of these (0.8%) were significantly influenced by both imatinib and omacetaxine treatment. k-means clustering and DAVID functional annotation showed expression changes in genes related to kinase binding and vacuole-related functions following imatinib treatment, whilst expression changes in genes related to cell division and apoptosis were evident following treatment with omacetaxine. The enrichment scores for these ontologies were very high (mostly >10).
Conclusions

Induction of gene expression changes related to different pathways following imatinib and omacetaxine treatment suggests that the cytotoxicity of such drugs may be differentially tolerated by individuals based on their genetic background.

Evaluation of segmentation algorithms for extraction of RNFL in OCT images

The thickness of the retinal nerve fiber layer (RFNL) has become a diagnose measure for glaucoma assessment. To measure this thickness, accurate segmentation of the RFNL in optical coherence tomography (OCT) images is essential. Identification of a suitable segmentation algorithm will facilitate the enhancement of the RNFL thickness measurement accuracy. This paper investigates the performance of six algorithms in the segmentation of RNFL in OCT images. The algorithms are: normalised cuts, region growing, k-means clustering, active contour, level sets segmentation: Piecewise Gaussian Method (PGM) and Kernelized Method (KM). The performance of the six algorithms are determined through a set of experiments on OCT retinal images. An experimental procedure is used to measure the performance of the tested algorithms. The measured segmentation precision-recall results of the six algorithms are compared and discussed.

Neural network and interval type-2 fuzzy system for stock price forecasting

Stock price forecast has long been received special attention of investors and financial institutions. As stock prices are changeable over time and increasingly uncertain in modern financial markets, their forecasting becomes more important than ever before. A hybrid approach consisting of two components, a neural network and a fuzzy logic system, is proposed in this paper for stock price prediction. The first component of the hybrid, i.e. a feedforward neural network (FFNN), is used to select inputs that are highly relevant to the dependent variables. An interval type-2 fuzzy logic system (IT2 FLS) is employed as the second component of the hybrid forecasting method. The IT2 FLS’s parameters are initialized through deployment of the k-means clustering method and they are adjusted by the genetic algorithm. Experimental results demonstrate the efficiency of the FFNN input selection approach as it reduces the complexity and increase the accuracy of the forecasting models. In addition, IT2 FLS outperforms the widely used type-1 FLS and FFNN models in stock price forecasting. The combination of the FFNN and the IT2 FLS produces dominant forecasting accuracy compared to employing only the IT2 FLSs without the FFNN input selection.

An evolving possibilistic fuzzy modeling approach for value-at-risk estimation

Market risk exposure plays a key role for nancial institutions risk management. A possible measure for this exposure is to evaluate losses likely to incurwhen the price of the portfolio's assets declines using Value-at-Risk (VaR) estimates, one of the most prominent measure of nancial downside market risk. This paper suggests an evolving possibilistic fuzzy modeling approach for VaR estimation. The approach is based on an extension of the possibilistic fuzzy c-means clustering and functional fuzzy rule-based modeling, which employs memberships and typicalities to update clusters and creates new clusters based on a statistical control distance-based criteria. ePFM also uses an utility measure to evaluate the quality of the current cluster structure. Computational experiments consider data of the main global equity market indexes of United States, London, Germany, Spain and Brazil from January 2000 to December 2012 for VaR estimation using ePFM, traditional VaR benchmarks such as Historical Simulation, GARCH, EWMA, and Extreme Value Theory and state of the art evolving approaches. The results show that ePFM is a potential candidate for VaR modeling, with better performance than alternative approaches.

Causas de variação nos preços de bovinos nelore elite no Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Análise multivariada e variabilidade espacial na estimativa da erodibilidade de um argissolo vermelho-amarelo

A erodibilidade é um fator de extrema importância na caracterização da perda de solo, representando os processos que regulam a infiltração de água e sua resistência à desagregação e o transporte de partículas. Assim, por meio da análise de dependência espacial dos componentes principais da erodibilidade (fator K), objetivou-se estimar a erodibilidade do solo em uma área de nascentes da microbacia do Córrego do Tijuco, Monte Alto-SP, e analisar a variabilidade espacial das variáveis granulométricas do solo ao longo do relevo. A erodibilidade média da área foi considerada alta, e a análise de agrupamento k-means apontou para uma formação de cinco grupos: no primeiro, os altos teores de areia grossa (AG) e média (AM) condicionaram sua distribuição nas áreas planas; o segundo, caracterizado pelo alto teor de areia fina (AF), distribui-se nos declives mais convexos; o terceiro, com altos teores de silte e areia muito fina (AMF), concentrou-se nos maiores declives e concavidades; o quarto, com maior teor de argila, seguiu as zonas de escoamento de água; e o quinto, com alto teor de matéria orgânica (MO) e areia grossa (AG), distribui-se nas proximidades da zona urbana. A análise de componentes principais (ACP) mostrou quatro componentes com 87,4 % das informações, sendo o primeiro componente principal (CP1) discriminado pelo transporte seletivo de partículas principalmente em zonas pontuais de maior declividade e acúmulo de sedimentos; o segundo (CP2), discriminado pela baixa coesão entre as partículas, mostra acúmulo da areia fina nas áreas de menor cota em toda a área de concentração de água; o terceiro (CP3), discriminado pela maior agregação do solo, concentra-se principalmente nas bases de grandes declives; e o quarto (CP4), discriminado pela areia muito fina, distribui-se ao longo das declividades nas maiores altitudes. Os resultados sugerem o comportamento granulométrico do solo, que se mostra suscetível ao processo erosivo devido às condições texturais superficiais e à movimentação do relevo.

The variability and predictors of quality of AIDS care services in Brazil

Background: Since establishing universal free access to antiretroviral therapy in 1996, the Brazilian Health System has increased the number of centers providing HIV/AIDS outpatient care from 33 to 540. There had been no formal monitoring of the quality of these services until a survey of 336 AIDS health centers across 7 Brazilian states was undertaken in 2002. Managers of the services were asked to assess their clinics according to parameters of service inputs and service delivery processes. This report analyzes the survey results and identifies predictors of the overall quality of service delivery.Methods: The survey involved completion of a multiple-choice questionnaire comprising 107 parameters of service inputs and processes of delivering care, with responses assessed according to their likely impact on service quality using a 3-point scale. K-means clustering was used to group these services according to their scored responses. Logistic regression analysis was performed to identify predictors of high service quality.Results: The questionnaire was completed by 95.8% (322) of the managers of the sites surveyed. Most sites scored about 50% of the benchmark expectation. K-means clustering analysis identified four quality levels within which services could be grouped: 76 services (24%) were classed as level 1 (best), 53 (16%) as level 2 (medium), 113 (35%) as level 3 (poor), and 80 (25%) as level 4 (very poor). Parameters of service delivery processes were more important than those relating to service inputs for determining the quality classification. Predictors of quality services included larger care sites, specialization for HIV/AIDS, and location within large municipalities.Conclusion: The survey demonstrated highly variable levels of HIV/AIDS service quality across the sites. Many sites were found to have deficiencies in the processes of service delivery processes that could benefit from quality improvement initiatives. These findings could have implications for how HIV/AIDS services are planned in Brazil to achieve quality standards, such as for where service sites should be located, their size and staffing requirements. A set of service delivery indicators has been identified that could be used for routine monitoring of HIV/AIDS service delivery for HIV/AIDS in Brazil (and potentially in other similar settings).

Damage detection in a benchmark structure using AR-ARX models and statistical pattern recognition

Structural health monitoring (SHM) is related to the ability of monitoring the state and deciding the level of damage or deterioration within aerospace, civil and mechanical systems. In this sense, this paper deals with the application of a two-step auto-regressive and auto-regressive with exogenous inputs (AR-ARX) model for linear prediction of damage diagnosis in structural systems. This damage detection algorithm is based on the. monitoring of residual error as damage-sensitive indexes, obtained through vibration response measurements. In complex structures there are. many positions under observation and a large amount of data to be handed, making difficult the visualization of the signals. This paper also investigates data compression by using principal component analysis. In order to establish a threshold value, a fuzzy c-means clustering is taken to quantify the damage-sensitive index in an unsupervised learning mode. Tests are made in a benchmark problem, as proposed by IASC-ASCE with different damage patterns. The diagnosis that was obtained showed high correlation with the actual integrity state of the structure. Copyright © 2007 by ABCM.

Ajuste de modelos não lineares e estimativas de parâmetros genéticos para produção de ovos de uma linhagem de poedeiras White Leghorn

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Metodologias para reconhecimento de padrões em sistemas SHM utilizando a técnica da Impedância Eletromecânica (E/M)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fibroblastos associados ao câncer e correlação com parãmetros patológicos em melanomas cutâneos caninos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise espacial e temporal de atributos do solo e da produtividade das culturas visando manejo específico em áreas agrícolas

Pós-graduação em Agronomia (Produção Vegetal) - FCAV