402 research outputs found

    Optimization Based Liver Contour Extraction of Abdominal CT Images

    Get PDF
    This paper introduces computer aided analysis system for diagnosis of liver abnormality in abdominal CT images. Segmenting the liver and visualizing the region of interest is a most challenging task in the field of cancer imaging, due to small observable changes between healthy and unhealthy liver. In this paper, hybrid approach for automatic extraction of liver contour is proposed. To obtain optimal threshold, the proposed work integrates segmentation method with optimization technique in order to provide better accuracy. This method uses bilateral filter for preprocessing and Fuzzy C means clustering (FCM) for segmentation. Mean Grey Wolf Optimization technique (mGWO) has been used to get the optimal threshold. This threshold is used for segmenting the region of interest. From the segmented output, largest connected region are identified using Label Connected Component (LCC) algorithm. The effectiveness of proposed method is quantitatively evaluated by comparing with ground truth obtained from radiologists. The performance criteria like dice coefficient, true positive error and misclassification rate are taken for evaluation

    G-protein-coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion

    Get PDF
    Triple-negative breast cancer (TNBC) accounts for 20% of breast cancer in women and lacks an effective targeted therapy. Therefore, finding common vulnerabilities in these tumors represents an opportunity for more effective treatment. Despite the growing appreciation of G-protein-coupled receptor (GPCR)-mediated signaling in cancer pathogenesis, very little is known about the role GPCRs play in TNBC. Using genomic information of human breast cancer, we have discovered that the orphan GPCR, G-protein-coupled receptor 161 (GPR161) is overexpressed specifically in TNBC and correlates with poor prognosis. Knockdown of GPR161 impairs proliferation of human basal breast cancer cell lines. Overexpression of GPR161 in human mammary epithelial cells increases cell proliferation, migration, intracellular accumulation of E-cadherin, and formation of multiacinar structures in 3D culture. GPR161 forms a signaling complex with the scaffold proteins beta-arrestin 2 and Ile Gln motif containing GTPase Activating Protein 1, a regulator of mammalian target of rapamycin complex 1 and E-cadherin. Consistently, GPR161 amplified breast tumors and cells overexpressing GPR161 activate mammalian target of rapamycin signaling and decrease Ile Gln motif containing GTPase Activating Protein 1 phosphorylation. Thus, we identify the orphan GPCR, GPR161, as an important regulator and a potential drug target for TNBC

    Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

    Get PDF
    Our understanding of the mechanisms by which ducts and lobules develop is derived from model organisms and three-dimensional (3D) cell culture models wherein mammalian epithelial cells undergo morphogenesis to form multicellular spheres with a hollow central lumen. However, the mechanophysical properties associated with epithelial morphogenesis are poorly understood. We performed multidimensional live-cell imaging analysis to track the morphogenetic process starting from a single cell to the development of a multicellular, spherical structure composed of polarized epithelial cells surrounding a hollow lumen. We report that in addition to actively maintaining apicobasal polarity, the structures underwent rotational motions at rates of 15-20 μm/h and the structures rotated 360° every 4 h during the early phase of morphogenesis. Rotational motion was independent of the cell cycle, but was blocked by loss of the epithelial polarity proteins Scribble or Pard3, or by inhibition of dynein-based microtubule motors. Interestingly, none of the structures derived from human cancer underwent rotational motion. We found a direct relationship between rotational motion and assembly of endogenous basement membrane matrix around the 3D structures, and that structures that failed to rotate were defective in weaving exogenous laminin matrix. Dissolution of basement membrane around mature, nonrotating acini restored rotational movement and the ability to assemble exogenous laminin. Thus, coordinated rotational movement is a unique mechanophysical process observed during normal 3D morphogenesis that regulates laminin matrix assembly and is lost in cancer-derived epithelial cells

    A novel role for 14-3-3σ in regulating epithelial cell polarity

    Get PDF
    The loss of epithelial polarity is thought to play an important role during mammary tumor progression. Using a unique transgenic mouse model of ErbB2-induced mammary tumorigenesis, we demonstrated previously that amplification of ErbB2 is frequently accompanied by loss of the 14-3-3σ gene. Here, we demonstrate that ectopic expression of 14-3-3σ results in restoration of epithelial polarity in ErbB2-transformed mammary tumor cells. We further demonstrate that targeted deletion of 14-3-3σ within primary mammary epithelial cells increases their proliferative capacity and adversely affects their ability to form polarized structures. Finally, we show that 14-3-3σ can specifically form complexes with Par3, a protein that is essential for the maintenance of a polarized epithelial state. Taken together, these observations suggest that 14-3-3σ plays a critical role in retaining epithelial polarity. © 2010 by Cold Spring Harbor Laboratory Press

    PROJECT PERFORMANCE: ROLE OF OPERATIONAL SAFETY, HEALTH PERFORMANCE AND SAFETY PREPARATION

    Get PDF
    Contemporary construction companies are placing emphasis on implementing various safety and health strategies in order to attain a favorable safety climate within the industry and enhance operational effectiveness. The purpose of this study is to examine the influence of operational safety (OS), health performance (HP), and safety preparation (SP) on the project performance of construction companies in Saudi Arabia. In order to effectively accomplish the stated objectives and yield optimal outcomes, data was gathered from a sample size of 316 employees employed in construction companies. The findings of the study emphasize that operating systems (OS), human resources practices (HP), and strategic planning (SP) have a significant influence on the project performance of construction companies. The mediation of open-source software (OSS) has demonstrated significant effects on the relationships between operating systems (OS), hardware providers (HP), software providers (SP), and platform providers (PP). This study renders a valuable contribution to the existing body of knowledge on safety by investigating the effects of pertinent factors within the construction industry. The results of this study provide valuable insights for professionals in the construction industry, enabling them to enhance the efficacy of safety management systems within their respective work environments. Furthermore, it serves as a driving force for the development of programs and policies aimed at facilitating the effective implementation of operating systems (OS), scheduling practices (SP), and health and safety protocols (HP) in order to attain optimal performance in construction projects

    WaveCNV: allele-specific copy number alterations in primary tumors and xenograft models from next-generation sequencing.

    Get PDF
    MotivationCopy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data.ResultsWe have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data.Availability and implementationSource code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented [email protected] informationSupplementary data are available at Bioinformatics online

    Financial correlations at ultra-high frequency: theoretical models and empirical estimation

    Full text link
    A detailed analysis of correlation between stock returns at high frequency is compared with simple models of random walks. We focus in particular on the dependence of correlations on time scales - the so-called Epps effect. This provides a characterization of stochastic models of stock price returns which is appropriate at very high frequency.Comment: 22 pages, 8 figures, 1 table, version to appear in EPJ

    Optimal Drug Regimen and Combined Drug Therapy and its Efficacy in the Treatment of COVID-19 : An Within-Host Modeling Study

    Full text link
    The COVID-19 pandemic has resulted in more than 30.35 million infections and 9, 50, 625 deaths in 212 countries over the last few months. Different drug intervention acting at multiple stages of pathogenesis of COVID-19 can substantially reduce the infection induced mortality. The current within-host mathematical modeling studies deals with the optimal drug regimen and the efficacy of combined therapy in treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Inteferon (INF) and Lopinavir/Ritonavir. It is concluded that these drug interventions when administered individually or in combination reduce the infected cells and viral load. Four scenarios involving administration of single drug intervention, two drug interventions, three drug interventions and all the four have been discussed. In all these scenarios the optimal drug regimen is proposed based on two methods. In the first method these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem is formulated. In this setting the optimal drug regimen is proposed. Later using the the comparative effectiveness method the optimal drug regimen is proposed based on basic reproduction number and viral load. The average infected cell count and viral load decreased the most when all the four interventions were applied together. On the other hand the average susceptible cell count decreased the best when Arbidol alone was administered. The basic reproduction number and viral count decreased the best when all the four interventions were applied together reinstating the fact obtained earlier in the optimal control setting. These findings may help physicians with decision making in treatment of life-threatening COVID-19 pneumonia.Comment: 16 pages, 13 figure

    Quantification of depth of anesthesia by nonlinear time series analysis of brain electrical activity

    Full text link
    We investigate several quantifiers of the electroencephalogram (EEG) signal with respect to their ability to indicate depth of anesthesia. For 17 patients anesthetized with Sevoflurane, three established measures (two spectral and one based on the bispectrum), as well as a phase space based nonlinear correlation index were computed from consecutive EEG epochs. In absence of an independent way to determine anesthesia depth, the standard was derived from measured blood plasma concentrations of the anesthetic via a pharmacokinetic/pharmacodynamic model for the estimated effective brain concentration of Sevoflurane. In most patients, the highest correlation is observed for the nonlinear correlation index D*. In contrast to spectral measures, D* is found to decrease monotonically with increasing (estimated) depth of anesthesia, even when a "burst-suppression" pattern occurs in the EEG. The findings show the potential for applications of concepts derived from the theory of nonlinear dynamics, even if little can be assumed about the process under investigation.Comment: 7 pages, 5 figure
    corecore