WorldWideScience

Sample records for differential co-expression analysis

  1. Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Li Z

    2017-06-01

    Full Text Available Zhen Li,1 Qianlan Yao,1 Songjian Zhao,1 Yin Wang,2,3 Yixue Li,1,4 Zhen Wang4 1School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 2Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 3Collaborative Innovation Center for Genetics and Development, Fudan University, 4Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Esophageal squamous cell carcinoma (ESCC is one of the most common malignancies worldwide and occurs at a relatively high frequency in People’s Republic of China. However, the molecular mechanism underlying ESCC is still unclear. In this study, the mRNA and long non-coding RNA (lncRNA expression profiles of ESCC were downloaded from the Gene Expression Omnibus database, and then differential co-expression analysis was used to reveal the altered co-expression relationship of gene pairs in ESCC tumors. A total of 3,709 mRNAs and 923 lncRNAs were differentially co-expressed between normal and tumor tissues, and we found that most of the gene pairs lost associations in the tumor tissues. The differential regulatory networking approach deciphered that transcriptional dysregulation was ubiquitous in ESCC, and most of the differentially regulated links were modulated by 37 TFs. Our study also found that two novel lncRNAs (ADAMTS9-AS1 and AP000696.2 might be essential in the development of ectoderm and epithelial cells, which could significantly stratify ESCC patients into high-risk and low-risk groups, and were much better than traditional clinical tumor markers. Further inspection of two risk groups showed that the changes in TF-target regulation in the high-risk patients were significantly higher than those in the low-risk patients. In addition, four signal transduction-related DCmRNAs (ERBB3, ENSA, KCNK7, MFSD5

  2. Dissection of regulatory networks that are altered in disease via differential co-expression.

    Directory of Open Access Journals (Sweden)

    David Amar

    Full Text Available Comparing the gene-expression profiles of sick and healthy individuals can help in understanding disease. Such differential expression analysis is a well-established way to find gene sets whose expression is altered in the disease. Recent approaches to gene-expression analysis go a step further and seek differential co-expression patterns, wherein the level of co-expression of a set of genes differs markedly between disease and control samples. Such patterns can arise from a disease-related change in the regulatory mechanism governing that set of genes, and pinpoint dysfunctional regulatory networks. Here we present DICER, a new method for detecting differentially co-expressed gene sets using a novel probabilistic score for differential correlation. DICER goes beyond standard differential co-expression and detects pairs of modules showing differential co-expression. The expression profiles of genes within each module of the pair are correlated across all samples. The correlation between the two modules, however, differs markedly between the disease and normal samples. We show that DICER outperforms the state of the art in terms of significance and interpretability of the detected gene sets. Moreover, the gene sets discovered by DICER manifest regulation by disease-specific microRNA families. In a case study on Alzheimer's disease, DICER dissected biological processes and protein complexes into functional subunits that are differentially co-expressed, thereby revealing inner structures in disease regulatory networks.

  3. Multiscale Embedded Gene Co-expression Network Analysis.

    Directory of Open Access Journals (Sweden)

    Won-Min Song

    2015-11-01

    Full Text Available Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3, the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA by: i introducing quality control of co-expression similarities, ii parallelizing embedded network construction, and iii developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs. We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA. MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

  4. Multiscale Embedded Gene Co-expression Network Analysis.

    Science.gov (United States)

    Song, Won-Min; Zhang, Bin

    2015-11-01

    Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

  5. A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.

    Science.gov (United States)

    Zhang, Qingyang

    2018-05-16

    Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

  6. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  7. Characterization of differentially expressed genes using high-dimensional co-expression networks

    DEFF Research Database (Denmark)

    Coelho Goncalves de Abreu, Gabriel; Labouriau, Rodrigo S.

    2010-01-01

    We present a technique to characterize differentially expressed genes in terms of their position in a high-dimensional co-expression network. The set-up of Gaussian graphical models is used to construct representations of the co-expression network in such a way that redundancy and the propagation...... that allow to make effective inference in problems with high degree of complexity (e.g. several thousands of genes) and small number of observations (e.g. 10-100) as typically occurs in high throughput gene expression studies. Taking advantage of the internal structure of decomposable graphical models, we...... construct a compact representation of the co-expression network that allows to identify the regions with high concentration of differentially expressed genes. It is argued that differentially expressed genes located in highly interconnected regions of the co-expression network are less informative than...

  8. [Weighted gene co-expression network analysis in biomedicine research].

    Science.gov (United States)

    Liu, Wei; Li, Li; Ye, Hua; Tu, Wei

    2017-11-25

    High-throughput biological technologies are now widely applied in biology and medicine, allowing scientists to monitor thousands of parameters simultaneously in a specific sample. However, it is still an enormous challenge to mine useful information from high-throughput data. The emergence of network biology provides deeper insights into complex bio-system and reveals the modularity in tissue/cellular networks. Correlation networks are increasingly used in bioinformatics applications. Weighted gene co-expression network analysis (WGCNA) tool can detect clusters of highly correlated genes. Therefore, we systematically reviewed the application of WGCNA in the study of disease diagnosis, pathogenesis and other related fields. First, we introduced principle, workflow, advantages and disadvantages of WGCNA. Second, we presented the application of WGCNA in disease, physiology, drug, evolution and genome annotation. Then, we indicated the application of WGCNA in newly developed high-throughput methods. We hope this review will help to promote the application of WGCNA in biomedicine research.

  9. Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

    Science.gov (United States)

    Xu, Fan; Yang, Jing; Chen, Jin; Wu, Qingyuan; Gong, Wei; Zhang, Jianguo; Shao, Weihua; Mu, Jun; Yang, Deyu; Yang, Yongtao; Li, Zhiwei; Xie, Peng

    2015-04-03

    Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

  10. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

    Directory of Open Access Journals (Sweden)

    DeYoung Joseph

    2009-08-01

    Full Text Available Abstract Background Amyotrophic Lateral Sclerosis (ALS is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients. Results Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4% showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA was used to find disease-related networks (modules and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls and third dataset (63 patients and 63 controls, thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS. Conclusion This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.

  11. Guidance for RNA-seq co-expression network construction and analysis: safety in numbers.

    Science.gov (United States)

    Ballouz, S; Verleyen, W; Gillis, J

    2015-07-01

    RNA-seq co-expression analysis is in its infancy and reasonable practices remain poorly defined. We assessed a variety of RNA-seq expression data to determine factors affecting functional connectivity and topology in co-expression networks. We examine RNA-seq co-expression data generated from 1970 RNA-seq samples using a Guilt-By-Association framework, in which genes are assessed for the tendency of co-expression to reflect shared function. Minimal experimental criteria to obtain performance on par with microarrays were >20 samples with read depth >10 M per sample. While the aggregate network constructed shows good performance (area under the receiver operator characteristic curve ∼0.71), the dependency on number of experiments used is nearly identical to that present in microarrays, suggesting thousands of samples are required to obtain 'gold-standard' co-expression. We find a major topological difference between RNA-seq and microarray co-expression in the form of low overlaps between hub-like genes from each network due to changes in the correlation of expression noise within each technology. jgillis@cshl.edu or sballouz@cshl.edu Networks are available at: http://gillislab.labsites.cshl.edu/supplements/rna-seq-networks/ and supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Co-expression network analysis of duplicate genes in maize (Zea mays L.) reveals no subgenome bias.

    Science.gov (United States)

    Li, Lin; Briskine, Roman; Schaefer, Robert; Schnable, Patrick S; Myers, Chad L; Flagel, Lex E; Springer, Nathan M; Muehlbauer, Gary J

    2016-11-04

    Gene duplication is prevalent in many species and can result in coding and regulatory divergence. Gene duplications can be classified as whole genome duplication (WGD), tandem and inserted (non-syntenic). In maize, WGD resulted in the subgenomes maize1 and maize2, of which maize1 is considered the dominant subgenome. However, the landscape of co-expression network divergence of duplicate genes in maize is still largely uncharacterized. To address the consequence of gene duplication on co-expression network divergence, we developed a gene co-expression network from RNA-seq data derived from 64 different tissues/stages of the maize reference inbred-B73. WGD, tandem and inserted gene duplications exhibited distinct regulatory divergence. Inserted duplicate genes were more likely to be singletons in the co-expression networks, while WGD duplicate genes were likely to be co-expressed with other genes. Tandem duplicate genes were enriched in the co-expression pattern where co-expressed genes were nearly identical for the duplicates in the network. Older gene duplications exhibit more extensive co-expression variation than younger duplications. Overall, non-syntenic genes primarily from inserted duplications show more co-expression divergence. Also, such enlarged co-expression divergence is significantly related to duplication age. Moreover, subgenome dominance was not observed in the co-expression networks - maize1 and maize2 exhibit similar levels of intra subgenome correlations. Intriguingly, the level of inter subgenome co-expression was similar to the level of intra subgenome correlations, and genes from specific subgenomes were not likely to be the enriched in co-expression network modules and the hub genes were not predominantly from any specific subgenomes in maize. Our work provides a comprehensive analysis of maize co-expression network divergence for three different types of gene duplications and identifies potential relationships between duplication types

  13. Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Borlawsky Tara B

    2010-10-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the most common adult leukemia. It is a highly heterogeneous disease, and can be divided roughly into indolent and progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH mutational status was found to be associated with patient survival outcome, and biomarkers linked to the IgVH status has been a focus in the CLL prognosis research field. However, biomarkers highly correlated with IgVH mutational status which can accurately predict the survival outcome are yet to be discovered. Results In this paper, we investigate the use of gene co-expression network analysis to identify potential biomarkers for CLL. Specifically we focused on the co-expression network involving ZAP70, a well characterized biomarker for CLL. We selected 23 microarray datasets corresponding to multiple types of cancer from the Gene Expression Omnibus (GEO and used the frequent network mining algorithm CODENSE to identify highly connected gene co-expression networks spanning the entire genome, then evaluated the genes in the co-expression network in which ZAP70 is involved. We then applied a set of feature selection methods to further select genes which are capable of predicting IgVH mutation status from the ZAP70 co-expression network. Conclusions We have identified a set of genes that are potential CLL prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient IgVH mutational status with high accuracies. Their prognostic capabilities were cross-validated by applying these biomarker candidates to classify patients into different outcome groups using a CLL microarray datasets with clinical information.

  14. Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

    Science.gov (United States)

    Han, Xinxin; Yin, Linlin; Xue, Hongwei

    2012-07-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

  15. Pathway enrichment and co-expression cluster analysis - FANTOM5 | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us FANTOM...lusters File URL: ftp://ftp.biosciencedbc.jp/archive/fantom5/datafiles/phase1.3/extra/Co-expression_clusters...ite Policy | Contact Us Pathway enrichment and co-expression cluster analysis - FANTOM5 | LSDB Archive ...

  16. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean) Cattle.

    Science.gov (United States)

    Lim, Dajeong; Lee, Seung-Hwan; Kim, Nam-Kuk; Cho, Yong-Min; Chai, Han-Ha; Seong, Hwan-Hoo; Kim, Heebal

    2013-01-01

    Marbling (intramuscular fat) is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the 'marbling score' trait and systemically analyzed the network topology in Hanwoo (Korean cattle). As a result, we determined 3 modules (gene groups) that showed statistically significant results for marbling score. In particular, one module (denoted as red) has a statistically significant result for marbling score (p = 0.008) and intramuscular fat (p = 0.02) and water capacity (p = 0.006). From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA) have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  17. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean Cattle

    Directory of Open Access Journals (Sweden)

    Dajeong Lim

    2013-01-01

    Full Text Available Marbling (intramuscular fat is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the ‘marbling score’ trait and systemically analyzed the network topology in Hanwoo (Korean cattle. As a result, we determined 3 modules (gene groups that showed statistically significant results for marbling score. In particular, one module (denoted as red has a statistically significant result for marbling score (p = 0.008 and intramuscular fat (p = 0.02 and water capacity (p = 0.006. From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  18. An extensive (co-expression analysis tool for the cytochrome P450 superfamily in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Provart Nicholas J

    2008-04-01

    Full Text Available Abstract Background Sequencing of the first plant genomes has revealed that cytochromes P450 have evolved to become the largest family of enzymes in secondary metabolism. The proportion of P450 enzymes with characterized biochemical function(s is however very small. If P450 diversification mirrors evolution of chemical diversity, this points to an unexpectedly poor understanding of plant metabolism. We assumed that extensive analysis of gene expression might guide towards the function of P450 enzymes, and highlight overlooked aspects of plant metabolism. Results We have created a comprehensive database, 'CYPedia', describing P450 gene expression in four data sets: organs and tissues, stress response, hormone response, and mutants of Arabidopsis thaliana, based on public Affymetrix ATH1 microarray expression data. P450 expression was then combined with the expression of 4,130 re-annotated genes, predicted to act in plant metabolism, for co-expression analyses. Based on the annotation of co-expressed genes from diverse pathway annotation databases, co-expressed pathways were identified. Predictions were validated for most P450s with known functions. As examples, co-expression results for P450s related to plastidial functions/photosynthesis, and to phenylpropanoid, triterpenoid and jasmonate metabolism are highlighted here. Conclusion The large scale hypothesis generation tools presented here provide leads to new pathways, unexpected functions, and regulatory networks for many P450s in plant metabolism. These can now be exploited by the community to validate the proposed functions experimentally using reverse genetics, biochemistry, and metabolic profiling.

  19. Weighted gene co-expression network analysis reveals potential genes involved in early metamorphosis process in sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Li, Yongxin; Kikuchi, Mani; Li, Xueyan; Gao, Qionghua; Xiong, Zijun; Ren, Yandong; Zhao, Ruoping; Mao, Bingyu; Kondo, Mariko; Irie, Naoki; Wang, Wen

    2018-01-01

    Sea cucumbers, one main class of Echinoderms, have a very fast and drastic metamorphosis process during their development. However, the molecular basis under this process remains largely unknown. Here we systematically examined the gene expression profiles of Japanese common sea cucumber (Apostichopus japonicus) for the first time by RNA sequencing across 16 developmental time points from fertilized egg to juvenile stage. Based on the weighted gene co-expression network analysis (WGCNA), we identified 21 modules. Among them, MEdarkmagenta was highly expressed and correlated with the early metamorphosis process from late auricularia to doliolaria larva. Furthermore, gene enrichment and differentially expressed gene analysis identified several genes in the module that may play key roles in the metamorphosis process. Our results not only provide a molecular basis for experimentally studying the development and morphological complexity of sea cucumber, but also lay a foundation for improving its emergence rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

    Science.gov (United States)

    Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

    2017-12-20

    Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

  1. Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

    Science.gov (United States)

    Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

    2017-08-01

    This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  2. Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

    Science.gov (United States)

    Rodius, Sophie; Androsova, Ganna; Götz, Lou; Liechti, Robin; Crespo, Isaac; Merz, Susanne; Nazarov, Petr V.; de Klein, Niek; Jeanty, Céline; González-Rosa, Juan M.; Muller, Arnaud; Bernardin, Francois; Niclou, Simone P.; Vallar, Laurent; Mercader, Nadia; Ibberson, Mark; Xenarios, Ioannis; Azuaje, Francisco

    2016-05-01

    The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.

  3. Application of Weighted Gene Co-expression Network Analysis for Data from Paired Design.

    Science.gov (United States)

    Li, Jianqiang; Zhou, Doudou; Qiu, Weiliang; Shi, Yuliang; Yang, Ji-Jiang; Chen, Shi; Wang, Qing; Pan, Hui

    2018-01-12

    Investigating how genes jointly affect complex human diseases is important, yet challenging. The network approach (e.g., weighted gene co-expression network analysis (WGCNA)) is a powerful tool. However, genomic data usually contain substantial batch effects, which could mask true genomic signals. Paired design is a powerful tool that can reduce batch effects. However, it is currently unclear how to appropriately apply WGCNA to genomic data from paired design. In this paper, we modified the current WGCNA pipeline to analyse high-throughput genomic data from paired design. We illustrated the modified WGCNA pipeline by analysing the miRNA dataset provided by Shiah et al. (2014), which contains forty oral squamous cell carcinoma (OSCC) specimens and their matched non-tumourous epithelial counterparts. OSCC is the sixth most common cancer worldwide. The modified WGCNA pipeline identified two sets of novel miRNAs associated with OSCC, in addition to the existing miRNAs reported by Shiah et al. (2014). Thus, this work will be of great interest to readers of various scientific disciplines, in particular, genetic and genomic scientists as well as medical scientists working on cancer.

  4. Integrative analysis of many weighted co-expression networks using tensor computation.

    Directory of Open Access Journals (Sweden)

    Wenyuan Li

    2011-06-01

    Full Text Available The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks.

  5. Meta-analysis of inter-species liver co-expression networks elucidates traits associated with common human diseases.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2009-12-01

    Full Text Available Co-expression networks are routinely used to study human diseases like obesity and diabetes. Systematic comparison of these networks between species has the potential to elucidate common mechanisms that are conserved between human and rodent species, as well as those that are species-specific characterizing evolutionary plasticity. We developed a semi-parametric meta-analysis approach for combining gene-gene co-expression relationships across expression profile datasets from multiple species. The simulation results showed that the semi-parametric method is robust against noise. When applied to human, mouse, and rat liver co-expression networks, our method out-performed existing methods in identifying gene pairs with coherent biological functions. We identified a network conserved across species that highlighted cell-cell signaling, cell-adhesion and sterol biosynthesis as main biological processes represented in genome-wide association study candidate gene sets for blood lipid levels. We further developed a heterogeneity statistic to test for network differences among multiple datasets, and demonstrated that genes with species-specific interactions tend to be under positive selection throughout evolution. Finally, we identified a human-specific sub-network regulated by RXRG, which has been validated to play a different role in hyperlipidemia and Type 2 diabetes between human and mouse. Taken together, our approach represents a novel step forward in integrating gene co-expression networks from multiple large scale datasets to leverage not only common information but also differences that are dataset-specific.

  6. Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Chaoqun Li

    2018-01-01

    Full Text Available Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice. Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to

  7. Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus.

    Science.gov (United States)

    Li, Chaoqun; Cao, Feifei; Li, Shengli; Huang, Shenglin; Li, Wei; Abumaria, Nashat

    2017-01-01

    Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA) has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice). Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to stress

  8. The Arabidopsis co-expression tool (act): a WWW-based tool and database for microarray-based gene expression analysis

    DEFF Research Database (Denmark)

    Jen, C. H.; Manfield, I. W.; Michalopoulos, D. W.

    2006-01-01

    be examined using the novel clique finder tool to determine the sets of genes most likely to be regulated in a similar manner. In combination, these tools offer three levels of analysis: creation of correlation lists of co-expressed genes, refinement of these lists using two-dimensional scatter plots......We present a new WWW-based tool for plant gene analysis, the Arabidopsis Co-Expression Tool (act) , based on a large Arabidopsis thaliana microarray data set obtained from the Nottingham Arabidopsis Stock Centre. The co-expression analysis tool allows users to identify genes whose expression...

  9. Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.

    Science.gov (United States)

    Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N; Jones, Byron C; Lu, Lu; Wang, Xusheng

    2018-01-01

    Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

  10. Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

    Directory of Open Access Journals (Sweden)

    Jie Luo

    2018-04-01

    Full Text Available Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1, down-regulation in NOE but rescue in RSE (pattern 2, up-regulation in both restraint stress followed by a saline injection (RSS and NOE, and further amplification in RSE (pattern 3, and up-regulation in RSS but reduction in both NOE and RSE (pattern 4. We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

  11. In-silico gene co-expression network analysis in Paracoccidioides brasiliensis with reference to haloacid dehalogenase superfamily hydrolase gene

    Directory of Open Access Journals (Sweden)

    Raghunath Satpathy

    2015-01-01

    Full Text Available Context: Paracoccidioides brasiliensis, a dimorphic fungus is the causative agent of paracoccidioidomycosis, a disease globally affecting millions of people. The haloacid dehalogenase (HAD superfamily hydrolases enzyme in the fungi, in particular, is known to be responsible in the pathogenesis by adhering to the tissue. Hence, identification of novel drug targets is essential. Aims: In-silico based identification of co-expressed genes along with HAD superfamily hydrolase in P. brasiliensis during the morphogenesis from mycelium to yeast to identify possible genes as drug targets. Materials and Methods: In total, four datasets were retrieved from the NCBI-gene expression omnibus (GEO database, each containing 4340 genes, followed by gene filtration expression of the data set. Further co-expression (CE study was performed individually and then a combination these genes were visualized in the Cytoscape 2. 8.3. Statistical Analysis Used: Mean and standard deviation value of the HAD superfamily hydrolase gene was obtained from the expression data and this value was subsequently used for the CE calculation purpose by selecting specific correlation power and filtering threshold. Results: The 23 genes that were thus obtained are common with respect to the HAD superfamily hydrolase gene. A significant network was selected from the Cytoscape network visualization that contains total 7 genes out of which 5 genes, which do not have significant protein hits, obtained from gene annotation of the expressed sequence tags by BLAST X. For all the protein PSI-BLAST was performed against human genome to find the homology. Conclusions: The gene co-expression network was obtained with respect to HAD superfamily dehalogenase gene in P. Brasiliensis.

  12. Weighted Gene Co-expression Network Analysis of the Dioscin Rich Medicinal Plant Dioscorea nipponica

    Directory of Open Access Journals (Sweden)

    Wei Sun

    2017-06-01

    Full Text Available Dioscorea contains critically important species which can be used as staple foods or sources of bioactive substances, including Dioscorea nipponica, which has been used to develop highly successful drugs to treat cardiovascular disease. Its major active ingredients are thought to be sterol compounds such as diosgenin, which has been called “medicinal gold” because of its valuable properties. However, reliance on naturally growing plants as a production system limits the potential use of D. nipponica, raising interest in engineering metabolic pathways to enhance the production of secondary metabolites. However, the biosynthetic pathway of diosgenin is still poorly understood, and D. nipponica is poorly characterized at a molecular level, hindering in-depth investigation. In the present work, the RNAs from five organs and seven methyl jasmonate treated D. nipponica rhizomes were sequenced using the Illumina high-throughput sequencing platform, yielding 52 gigabases of data, which were pooled and assembled into a reference transcriptome. Four hundred and eighty two genes were found to be highly expressed in the rhizomes, and these genes are mainly involved in stress response and transcriptional regulation. Based on their expression patterns, 36 genes were selected for further investigation as candidate genes involved in dioscin biosynthesis. Constructing co-expression networks based on significant changes in gene expression revealed 15 gene modules. Of these, four modules with properties correlating to dioscin regulation and biosynthesis, consisting of 4,665 genes in total, were selected for further functional investigation. These results improve our understanding of dioscin biosynthesis in this important medicinal plant and will help guide more intensive investigations.

  13. Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

    Science.gov (United States)

    Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

    2017-11-13

    The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly

  14. Comprehensive analysis of coding-lncRNA gene co-expression network uncovers conserved functional lncRNAs in zebrafish.

    Science.gov (United States)

    Chen, Wen; Zhang, Xuan; Li, Jing; Huang, Shulan; Xiang, Shuanglin; Hu, Xiang; Liu, Changning

    2018-05-09

    Zebrafish is a full-developed model system for studying development processes and human disease. Recent studies of deep sequencing had discovered a large number of long non-coding RNAs (lncRNAs) in zebrafish. However, only few of them had been functionally characterized. Therefore, how to take advantage of the mature zebrafish system to deeply investigate the lncRNAs' function and conservation is really intriguing. We systematically collected and analyzed a series of zebrafish RNA-seq data, then combined them with resources from known database and literatures. As a result, we obtained by far the most complete dataset of zebrafish lncRNAs, containing 13,604 lncRNA genes (21,128 transcripts) in total. Based on that, a co-expression network upon zebrafish coding and lncRNA genes was constructed and analyzed, and used to predict the Gene Ontology (GO) and the KEGG annotation of lncRNA. Meanwhile, we made a conservation analysis on zebrafish lncRNA, identifying 1828 conserved zebrafish lncRNA genes (1890 transcripts) that have their putative mammalian orthologs. We also found that zebrafish lncRNAs play important roles in regulation of the development and function of nervous system; these conserved lncRNAs present a significant sequential and functional conservation, with their mammalian counterparts. By integrative data analysis and construction of coding-lncRNA gene co-expression network, we gained the most comprehensive dataset of zebrafish lncRNAs up to present, as well as their systematic annotations and comprehensive analyses on function and conservation. Our study provides a reliable zebrafish-based platform to deeply explore lncRNA function and mechanism, as well as the lncRNA commonality between zebrafish and human.

  15. Co-expression network analysis to identify pluripotency biomarkers in bovine and porcine embryos

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Freude, Karla Kristine; Hall, Vanessa Jane

    Differentiated somatic cells can be reprogrammed in induced pluripotent stem cells (iPSCs); a cell type with great potentials in regenerative medicine and in vitro disease modeling. In the pig, we have developed iPSCs, but proper culture conditions for maintaining pluripotency over time are still...... lacking. Hence, there is a need for a more fundamental dissection of the pluripotency apparatus in the pig as well as in cattle. The aim of this study is to analyze RNA-seq data to increase the knowledge about biological pathways in porcine and bovine embryonic pluripotent cell populations exploiting...... the mouse data as proof of principle. In particular we studied cell populations from three different stages of pluripotency after fertilization: the inner cell mass, the epithelial epiblast and the gastrulating epiblast. Reads quality was checked with FASTQC, then the reads were pre-processed using Prinseq...

  16. Comparative transcriptome and gene co-expression network analysis reveal genes and signaling pathways adaptively responsive to varied adverse stresses in the insect fungal pathogen, Beauveria bassiana.

    Science.gov (United States)

    He, Zhangjiang; Zhao, Xin; Lu, Zhuoyue; Wang, Huifang; Liu, Pengfei; Zeng, Fanqin; Zhang, Yongjun

    2018-01-01

    Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. The fungal pathogen unavoidably encounters a variety of adverse environmental stresses and defense response from the host insects during application of the fungal agents. However, few are known about the transcription response of the fungus to respond or adapt varied adverse stresses. Here, we comparatively analyzed the transcriptome of B. bassiana in globe genome under the varied stationary-phase stresses including osmotic agent (0.8 M NaCl), high temperature (32 °C), cell wall-perturbing agent (Congo red), and oxidative agents (H 2 O 2 or menadione). Total of 12,412 reads were obtained, and mapped to the 6767 genes of the B. bassiana. All of these stresses caused transcription responses involved in basal metabolism, cell wall construction, stress response or cell rescue/detoxification, signaling transduction and gene transcription regulation, and likely other cellular processes. An array of genes displayed similar transcription patterns in response to at least two of the five stresses, suggesting a shared transcription response to varied adverse stresses. Gene co-expression network analysis revealed that mTOR signaling pathway, but not HOG1 MAP kinase pathway, played a central role in regulation the varied adverse stress responses, which was verified by RNAi-mediated knockdown of TOR1. Our findings provided an insight of transcription response and gene co-expression network of B. bassiana in adaptation to varied environments. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Disease gene characterization through large-scale co-expression analysis.

    Directory of Open Access Journals (Sweden)

    Allen Day

    2009-12-01

    Full Text Available In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET.Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format. The size of Celsius makes UGET a powerful gene characterization tool. Using a small seed list of known cartilage-selective genes, UGET extended the list of known genes by identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested were validated by qPCR including the novel cartilage-specific genes SDK2 and FLJ41170. In addition, we retrospectively tested UGET and other gene expression based prioritization tools to identify disease-causing genes within known linkage intervals. We first demonstrated this utility with UGET using genetically heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric disorders and type 2 limb girdle muscular dystrophy (LGMD2 and then compared UGET to other gene expression based prioritization programs which use small but discrete and well annotated datasets. Finally, we observed a significantly higher gene correlation shared between genes in disease networks associated with similar complex or Mendelian disorders.UGET is an invaluable resource for a geneticist that permits the rapid inclusion of expression criteria from one to hundreds of genes in genomic intervals linked to disease. By using thousands of arrays UGET annotates and prioritizes genes better than other tools especially with rare tissue disorders or complex multi-tissue biological processes. This information can be critical in prioritization of candidate genes for sequence analysis.

  18. Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery.

    Science.gov (United States)

    Jia, Zhilong; Liu, Ying; Guan, Naiyang; Bo, Xiaochen; Luo, Zhigang; Barnes, Michael R

    2016-05-27

    Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context. We demonstrate that the analysis of co-expressed genes may be a critical first step towards illumination of both disease pathology and mode of drug action. We achieve this using a novel framework, co-expressed gene-set enrichment analysis (cogena) for co-expression analysis of gene expression signatures and gene set enrichment analysis of co-expressed genes. The cogena framework enables simultaneous, pathway driven, disease and drug repositioning analysis. Cogena can be used to illuminate coordinated changes within disease transcriptomes and identify drugs acting mechanistically within this framework. We illustrate this using a psoriatic skin transcriptome, as an exemplar, and recover two widely used Psoriasis drugs (Methotrexate and Ciclosporin) with distinct modes of action. Cogena out-performs the results of Connectivity Map and NFFinder webservers in similar disease transcriptome analyses. Furthermore, we investigated the literature support for the other top-ranked compounds to treat psoriasis and showed how the outputs of cogena analysis can contribute new insight to support the progression of drugs into the clinic. We have made cogena freely available within Bioconductor or https://github.com/zhilongjia/cogena . In conclusion, by targeting co-expressed genes within disease transcriptomes, cogena offers novel biological insight, which can be effectively harnessed for drug discovery and

  19. Evolution, functional differentiation, and co-expression of the RLK gene family revealed in Jilin ginseng, Panax ginseng C.A. Meyer.

    Science.gov (United States)

    Lin, Yanping; Wang, Kangyu; Li, Xiangyu; Sun, Chunyu; Yin, Rui; Wang, Yanfang; Wang, Yi; Zhang, Meiping

    2018-02-21

    Most genes in a genome exist in the form of a gene family; therefore, it is necessary to have knowledge of how a gene family functions to comprehensively understand organismal biology. The receptor-like kinase (RLK)-encoding gene family is one of the most important gene families in plants. It plays important roles in biotic and abiotic stress tolerances, and growth and development. However, little is known about the functional differentiation and relationships among the gene members within a gene family in plants. This study has isolated 563 RLK genes (designated as PgRLK genes) expressed in Jilin ginseng (Panax ginseng C.A. Meyer), investigated their evolution, and deciphered their functional diversification and relationships. The PgRLK gene family is highly diverged and formed into eight types. The LRR type is the earliest and most prevalent, while only the Lec type originated after P. ginseng evolved. Furthermore, although the members of the PgRLK gene family all encode receptor-like protein kinases and share conservative domains, they are functionally very diverse, participating in numerous biological processes. The expressions of different members of the PgRLK gene family are extremely variable within a tissue, at a developmental stage and in the same cultivar, but most of the genes tend to express correlatively, forming a co-expression network. These results not only provide a deeper and comprehensive understanding of the evolution, functional differentiation and correlation of a gene family in plants, but also an RLK genic resource useful for enhanced ginseng genetic improvement.

  20. Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis

    Directory of Open Access Journals (Sweden)

    Zhou X

    2018-05-01

    Full Text Available Xian-guo Zhou,1,2,* Xiao-liang Huang,1,2,* Si-yuan Liang,1–3 Shao-mei Tang,1,2 Si-kao Wu,1,2 Tong-tong Huang,1,2 Zeng-nan Mo,1,2,4 Qiu-yan Wang1,2,5 1Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 4Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi, Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 5Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China *These authors contributed equally to this work Introduction: Colorectal cancer (CRC is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression.Materials and methods: We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA to detect the pathological stage-related miRNA and gene modules and construct a miRNA–gene network. The Cancer Genome Atlas (TCGA colon adenocarcinoma (CAC RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and

  1. Gene co-expression analysis identifies gene clusters associated with isotropic and polarized growth in Aspergillus fumigatus conidia.

    Science.gov (United States)

    Baltussen, Tim J H; Coolen, Jordy P M; Zoll, Jan; Verweij, Paul E; Melchers, Willem J G

    2018-04-26

    Aspergillus fumigatus is a saprophytic fungus that extensively produces conidia. These microscopic asexually reproductive structures are small enough to reach the lungs. Germination of conidia followed by hyphal growth inside human lungs is a key step in the establishment of infection in immunocompromised patients. RNA-Seq was used to analyze the transcriptome of dormant and germinating A. fumigatus conidia. Construction of a gene co-expression network revealed four gene clusters (modules) correlated with a growth phase (dormant, isotropic growth, polarized growth). Transcripts levels of genes encoding for secondary metabolites were high in dormant conidia. During isotropic growth, transcript levels of genes involved in cell wall modifications increased. Two modules encoding for growth and cell cycle/DNA processing were associated with polarized growth. In addition, the co-expression network was used to identify highly connected intermodular hub genes. These genes may have a pivotal role in the respective module and could therefore be compelling therapeutic targets. Generally, cell wall remodeling is an important process during isotropic and polarized growth, characterized by an increase of transcripts coding for hyphal growth and cell cycle/DNA processing when polarized growth is initiated. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Genetic architecture of wood properties based on association analysis and co-expression networks in white spruce.

    Science.gov (United States)

    Lamara, Mebarek; Raherison, Elie; Lenz, Patrick; Beaulieu, Jean; Bousquet, Jean; MacKay, John

    2016-04-01

    Association studies are widely utilized to analyze complex traits but their ability to disclose genetic architectures is often limited by statistical constraints, and functional insights are usually minimal in nonmodel organisms like forest trees. We developed an approach to integrate association mapping results with co-expression networks. We tested single nucleotide polymorphisms (SNPs) in 2652 candidate genes for statistical associations with wood density, stiffness, microfibril angle and ring width in a population of 1694 white spruce trees (Picea glauca). Associations mapping identified 229-292 genes per wood trait using a statistical significance level of P wood associated genes and several known MYB and NAC regulators were identified as network hubs. The network revealed a link between the gene PgNAC8, wood stiffness and microfibril angle, as well as considerable within-season variation for both genetic control of wood traits and gene expression. Trait associations were distributed throughout the network suggesting complex interactions and pleiotropic effects. Our findings indicate that integration of association mapping and co-expression networks enhances our understanding of complex wood traits. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  3. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Science.gov (United States)

    Faggi, Fiorella; Codenotti, Silvia; Poliani, Pietro Luigi; Cominelli, Manuela; Chiarelli, Nicola; Colombi, Marina; Vezzoli, Marika; Monti, Eugenio; Bono, Federica; Tulipano, Giovanni; Fiorentini, Chiara; Zanola, Alessandra; Lo, Harriet P; Parton, Robert G; Keller, Charles; Fanzani, Alessandro

    2015-01-01

    The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3) in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS), an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC) expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  4. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Directory of Open Access Journals (Sweden)

    Fiorella Faggi

    Full Text Available The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3 in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS, an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  5. Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Zhifen Liu

    Full Text Available LncRNAs, which represent one of the most highly expressed classes of ncRNAs in the brain, are becoming increasingly interesting with regard to brain functions and disorders. However, changes in the expression of regulatory lncRNAs in Major Depressive Disorder (MDD have not yet been reported. Using microarrays, we profiled the expression of 34834 lncRNAs and 39224 mRNAs in peripheral blood sampled from MDD patients as well as demographically-matched controls. Among these, we found that 2007 lncRNAs and 1667 mRNAs were differentially expressed, 17 of which were documented as depression-related gene in previous studies. Gene Ontology (GO and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to fundamental metabolic processes and neurodevelopment diseases. To investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, we also constructed co-expression networks composed of the lncRNAs and mRNAs, which shows significant correlated patterns of expression. In the MDD-derived network, there were a greater number of nodes and connections than that in the control-derived network. The lncRNAs located at chr10:874695-874794, chr10:75873456-75873642, and chr3:47048304-47048512 may be important factors regulating the expression of mRNAs as they have previously been reported associations with MDD. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in MDD using microarray technology. We identified circulating lncRNAs that are aberrantly expressed in MDD and the results suggest that lncRNAs may contribute to the molecular pathogenesis of MDD.

  6. Co-expression analysis and identification of fecundity-related long non-coding RNAs in sheep ovaries.

    Science.gov (United States)

    Miao, Xiangyang; Luo, Qingmiao; Zhao, Huijing; Qin, Xiaoyu

    2016-12-16

    Small Tail Han sheep, including the FecB B FecB B (Han BB) and FecB + FecB + (Han++) genotypes, and Dorset sheep exhibit different fecundities. To identify novel long non-coding RNAs (lncRNAs) associated with sheep fecundity to better understand their molecular mechanisms, a genome-wide analysis of mRNAs and lncRNAs from Han BB, Han++ and Dorset sheep was performed. After the identification of differentially expressed mRNAs and lncRNAs, 16 significant modules were explored by using weighted gene coexpression network analysis (WGCNA) followed by functional enrichment analysis of the genes and lncRNAs in significant modules. Among these selected modules, the yellow and brown modules were significantly related to sheep fecundity. lncRNAs (e.g., NR0B1, XLOC_041882, and MYH15) in the yellow module were mainly involved in the TGF-β signalling pathway, and NYAP1 and BCORL1 were significantly associated with the oxytocin signalling pathway, which regulates several genes in the coexpression network of the brown module. Overall, we identified several gene modules associated with sheep fecundity, as well as networks consisting of hub genes and lncRNAs that may contribute to sheep prolificacy by regulating the target mRNAs related to the TGF-β and oxytocin signalling pathways. This study provides an alternative strategy for the identification of potential candidate regulatory lncRNAs.

  7. In silico identification of miRNAs and their target genes and analysis of gene co-expression network in saffron (Crocus sativus L.) stigma

    Science.gov (United States)

    Zinati, Zahra; Shamloo-Dashtpagerdi, Roohollah; Behpouri, Ali

    2016-01-01

    As an aromatic and colorful plant of substantive taste, saffron (Crocus sativus L.) owes such properties of matter to growing class of the secondary metabolites derived from the carotenoids, apocarotenoids. Regarding the critical role of microRNAs in secondary metabolic synthesis and the limited number of identified miRNAs in C. sativus, on the other hand, one may see the point how the characterization of miRNAs along with the corresponding target genes in C. sativus might expand our perspectives on the roles of miRNAs in carotenoid/apocarotenoid biosynthetic pathway. A computational analysis was used to identify miRNAs and their targets using EST (Expressed Sequence Tag) library from mature saffron stigmas. Then, a gene co- expression network was constructed to identify genes which are potentially involved in carotenoid/apocarotenoid biosynthetic pathways. EST analysis led to the identification of two putative miRNAs (miR414 and miR837-5p) along with the corresponding stem- looped precursors. To our knowledge, this is the first report on miR414 and miR837-5p in C. sativus. Co-expression network analysis indicated that miR414 and miR837-5p may play roles in C. sativus metabolic pathways and led to identification of candidate genes including six transcription factors and one protein kinase probably involved in carotenoid/apocarotenoid biosynthetic pathway. Presence of transcription factors, miRNAs and protein kinase in the network indicated multiple layers of regulation in saffron stigma. The candidate genes from this study may help unraveling regulatory networks underlying the carotenoid/apocarotenoid biosynthesis in saffron and designing metabolic engineering for enhanced secondary metabolites. PMID:28261627

  8. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    Science.gov (United States)

    Xiao, Xiaolin; Moreno-Moral, Aida; Rotival, Maxime; Bottolo, Leonardo; Petretto, Enrico

    2014-01-01

    Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states). Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks) that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted) networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based) and humans (mRNA-sequencing-based) and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue subnetwork of co-expressed

  9. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    Directory of Open Access Journals (Sweden)

    Xiaolin Xiao

    2014-01-01

    Full Text Available Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states. Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based and humans (mRNA-sequencing-based and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi

  10. Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.

    Science.gov (United States)

    Wada, Masayoshi; Takahashi, Hiroki; Altaf-Ul-Amin, Md; Nakamura, Kensuke; Hirai, Masami Y; Ohta, Daisaku; Kanaya, Shigehiko

    2012-07-15

    Operon-like arrangements of genes occur in eukaryotes ranging from yeasts and filamentous fungi to nematodes, plants, and mammals. In plants, several examples of operon-like gene clusters involved in metabolic pathways have recently been characterized, e.g. the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice. Such operon-like gene clusters are defined by their co-regulation or neighboring positions within immediate vicinity of chromosomal regions. A comprehensive analysis of the expression of neighboring genes therefore accounts a crucial step to reveal the complete set of operon-like gene clusters within a genome. Genome-wide prediction of operon-like gene clusters should contribute to functional annotation efforts and provide novel insight into evolutionary aspects acquiring certain biological functions as well. We predicted co-expressed gene clusters by comparing the Pearson correlation coefficient of neighboring genes and randomly selected gene pairs, based on a statistical method that takes false discovery rate (FDR) into consideration for 1469 microarray gene expression datasets of A. thaliana. We estimated that A. thaliana contains 100 operon-like gene clusters in total. We predicted 34 statistically significant gene clusters consisting of 3 to 22 genes each, based on a stringent FDR threshold of 0.1. Functional relationships among genes in individual clusters were estimated by sequence similarity and functional annotation of genes. Duplicated gene pairs (determined based on BLAST with a cutoff of EOperon-like clusters tend to include genes encoding bio-machinery associated with ribosomes, the ubiquitin/proteasome system, secondary metabolic pathways, lipid and fatty-acid metabolism, and the lipid transfer system. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. GeneCAT--novel webtools that combine BLAST and co-expression analyses

    DEFF Research Database (Denmark)

    Mutwil, Marek; Obro, Jens; Willats, William G T

    2008-01-01

    The gene co-expression analysis toolbox (GeneCAT) introduces several novel microarray data analyzing tools. First, the multigene co-expression analysis, combined with co-expressed gene networks, provides a more powerful data mining technique than standard, single-gene co-expression analysis. Second...... orthologs in the plant model organisms Arabidopsis thaliana and Hordeum vulgare (Barley). GeneCAT is equipped with expression data for the model plant A. thaliana, and first to introduce co-expression mining tools for the monocot Barley. GeneCAT is available at http://genecat.mpg.de....

  12. Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

    DEFF Research Database (Denmark)

    Wang, Weijing; Jiang, Wenjie; Hou, Lin

    2017-01-01

    BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis......) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database...

  13. Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

    Science.gov (United States)

    Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

    2018-01-01

    Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for

  14. Relation of Transcriptional Factors to the Expression and Activity of Cytochrome P450 and UDP-Glucuronosyltransferases 1A in Human Liver: Co-Expression Network Analysis.

    Science.gov (United States)

    Zhong, Shilong; Han, Weichao; Hou, Chuqi; Liu, Junjin; Wu, Lili; Liu, Menghua; Liang, Zhi; Lin, Haoming; Zhou, Lili; Liu, Shuwen; Tang, Lan

    2017-01-01

    Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles (n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs. The relationship among 17 defined TFs, CYPs/UGTs expression, and activity were evaluated in 30 liver samples from Chinese patients. The positive controls (e.g., PPARA, NR1I2, NR1I3) and hub TFs (NFIA, NR3C2, and AR) in the Grey sWGCNA Module were significantly and positively associated with CYPs/UGTs expression. And the cancer- or inflammation-related TFs (TEAD4, NFKB2, and NFKB1) were negatively associated with mRNA expression of CYP2C9/CYP2E1/UGT1A9. Furthermore, the effect of NR1I2, NR1I3, AR, TEAD4, and NFKB2 on CYP450/UGT1A gene transcription translated into moderate influences on enzyme activities. To our knowledge, this is the first study to integrate Gene Expression Omnibus (GEO) datasets and supervised weighted correlation network analysis (sWGCNA) for defining TFs potentially related to CYPs/UGTs. We detected several novel TFs involved in the regulatory network of hepatic CYPs and UGTs in humans. Further validation and investigation may reveal their exact mechanism of CYPs/UGTs regulation.

  15. Significance of Co-expression of Epidermal Growth Factor Receptor and Ki67 on Clinical Outcome in Patients With Anal Cancer Treated With Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811.

    Science.gov (United States)

    Doll, Corinne M; Moughan, Jennifer; Klimowicz, Alexander; Ho, Clement K; Kornaga, Elizabeth N; Lees-Miller, Susan P; Ajani, Jaffer A; Crane, Christopher H; Kachnic, Lisa A; Okawara, Gordon S; Berk, Lawrence B; Roof, Kevin S; Becker, Mark J; Grisell, David L; Ellis, Robert J; Sperduto, Paul W; Marsa, Gerald W; Guha, Chandan; Magliocco, Anthony M

    2017-03-01

    To measure co-expression of EGFR and Ki67 proteins in pretreatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5-fluorouracil/mitomycin-C/radiation therapy (Arm A) versus 5-fluorouracil/cisplatin/radiation therapy (Arm B), and to correlate expression with clinical outcome. EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis. The Ki67 score within EGFR high versus low areas (Ki67ratio in EGFR high:low ) in each tumor core was analyzed at the median, quartiles, and as a continuous variable. Associations between the tumor markers and clinical endpoints (overall and disease-free survival, locoregional and colostomy failure, and distant metastases) were explored. A total of 282 pretreatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFR high:low  ≥median had worse overall survival (hazard ratio 2.41, 95% confidence interval 1.38-4.19, P=.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFR high:low  ≥ median had a higher risk of a disease-free failure (hazard ratio 1.85, 95% confidence interval 1.18-2.92, P=.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. High Ki67ratio in EGFR high:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor

  16. LOFT differential pressure uncertainty analysis

    International Nuclear Information System (INIS)

    Evans, R.P.; Biladeau, G.L.; Quinn, P.A.

    1977-03-01

    A performance analysis of the LOFT differential pressure (ΔP) measurement is presented. Along with completed descriptions of test programs and theoretical studies that have been conducted on the ΔP, specific sources of measurement uncertainty are identified, quantified, and combined to provide an assessment of the ability of this measurement to satisfy the SDD 1.4.1C (June 1975) requirement of measurement of differential pressure

  17. Identification of PEG-induced water stress responsive transcripts using co-expression network in Eucalyptus grandis.

    Science.gov (United States)

    Ghosh Dasgupta, Modhumita; Dharanishanthi, Veeramuthu

    2017-09-05

    Ecophysiological studies in Eucalyptus have shown that water is the principal factor limiting stem growth. Effect of water deficit conditions on physiological and biochemical parameters has been extensively reported in Eucalyptus. The present study was conducted to identify major polyethylene glycol induced water stress responsive transcripts in Eucalyptus grandis using gene co-expression network. A customized array representing 3359 water stress responsive genes was designed to document their expression in leaves of E. grandis cuttings subjected to -0.225MPa of PEG treatment. The differentially expressed transcripts were documented and significantly co-expressed transcripts were used for construction of network. The co-expression network was constructed with 915 nodes and 3454 edges with degree ranging from 2 to 45. Ninety four GO categories and 117 functional pathways were identified in the network. MCODE analysis generated 27 modules and module 6 with 479 nodes and 1005 edges was identified as the biologically relevant network. The major water responsive transcripts represented in the module included dehydrin, osmotin, LEA protein, expansin, arabinogalactans, heat shock proteins, major facilitator proteins, ARM repeat proteins, raffinose synthase, tonoplast intrinsic protein and transcription factors like DREB2A, ARF9, AGL24, UNE12, WLIM1 and MYB66, MYB70, MYB 55, MYB 16 and MYB 103. The coordinated analysis of gene expression patterns and coexpression networks developed in this study identified an array of transcripts that may regulate PEG induced water stress responses in E. grandis. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Co-Expression of Neighboring Genes in the Zebrafish (Danio rerio Genome

    Directory of Open Access Journals (Sweden)

    Daryi Wang

    2009-08-01

    Full Text Available Neighboring genes in the eukaryotic genome have a tendency to express concurrently, and the proximity of two adjacent genes is often considered a possible explanation for their co-expression behavior. However, the actual contribution of the physical distance between two genes to their co-expression behavior has yet to be defined. To further investigate this issue, we studied the co-expression of neighboring genes in zebrafish, which has a compact genome and has experienced a whole genome duplication event. Our analysis shows that the proportion of highly co-expressed neighboring pairs (Pearson’s correlation coefficient R>0.7 is low (0.24% ~ 0.67%; however, it is still significantly higher than that of random pairs. In particular, the statistical result implies that the co-expression tendency of neighboring pairs is negatively correlated with their physical distance. Our findings therefore suggest that physical distance may play an important role in the co-expression of neighboring genes. Possible mechanisms related to the neighboring genes’ co-expression are also discussed.

  19. Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Oyang Yen-Jen

    2010-10-01

    Full Text Available Abstract Background Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.

  20. Elucidating gene function and function evolution through comparison of co-expression networks in plants

    Directory of Open Access Journals (Sweden)

    Marek eMutwil

    2014-08-01

    Full Text Available The analysis of gene expression data has shown that transcriptionally coordinated (co-expressed genes are often functionally related, enabling scientists to use expression data in gene function prediction. This Focused Review discusses our original paper (Large-scale co-expression approach to dissect secondary cell wall formation across plant species, Frontiers in Plant Science 2:23. In this paper we applied cross-species analysis to co-expression networks of genes involved in cellulose biosynthesis. We show that the co-expression networks from different species are highly similar, indicating that whole biological pathways are conserved across species. This finding has two important implications. First, the analysis can transfer gene function annotation from well-studied plants, such as Arabidopsis, to other, uncharacterized plant species. As the analysis finds genes that have similar sequence and similar expression pattern across different organisms, functionally equivalent genes can be identified. Second, since co-expression analyses are often noisy, a comparative analysis should have higher performance, as parts of co-expression networks that are conserved are more likely to be functionally relevant. In this Focused Review, we outline the comparative analysis done in the original paper and comment on the recent advances and approaches that allow comparative analyses of co-function networks. We hypothesize that, in comparison to simple co-expression analysis, comparative analysis would yield more accurate gene function predictions. Finally, by combining comparative analysis with genomic information of green plants, we propose a possible composition of cellulose biosynthesis machinery during earlier stages of plant evolution.

  1. Multidimensional real analysis I differentiation

    CERN Document Server

    Duistermaat, J J; van Braam Houckgeest, J P

    2004-01-01

    Part one of the authors' comprehensive and innovative work on multidimensional real analysis. This book is based on extensive teaching experience at Utrecht University and gives a thorough account of differential analysis in multidimensional Euclidean space. It is an ideal preparation for students who wish to go on to more advanced study. The notation is carefully organized and all proofs are clean, complete and rigorous. The authors have taken care to pay proper attention to all aspects of the theory. In many respects this book presents an original treatment of the subject and it contains man

  2. Applied analysis and differential equations

    CERN Document Server

    Cârj, Ovidiu

    2007-01-01

    This volume contains refereed research articles written by experts in the field of applied analysis, differential equations and related topics. Well-known leading mathematicians worldwide and prominent young scientists cover a diverse range of topics, including the most exciting recent developments. A broad range of topics of recent interest are treated: existence, uniqueness, viability, asymptotic stability, viscosity solutions, controllability and numerical analysis for ODE, PDE and stochastic equations. The scope of the book is wide, ranging from pure mathematics to various applied fields such as classical mechanics, biomedicine, and population dynamics.

  3. Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Shivalika Pathania

    2016-08-01

    Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

  4. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

    Science.gov (United States)

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

  5. Differential Fault Analysis on CLEFIA

    Science.gov (United States)

    Chen, Hua; Wu, Wenling; Feng, Dengguo

    CLEFIA is a new 128-bit block cipher proposed by SONY corporation recently. The fundamental structure of CLEFIA is a generalized Feistel structure consisting of 4 data lines. In this paper, the strength of CLEFIA against the differential fault attack is explored. Our attack adopts the byte-oriented model of random faults. Through inducing randomly one byte fault in one round, four bytes of faults can be simultaneously obtained in the next round, which can efficiently reduce the total induce times in the attack. After attacking the last several rounds' encryptions, the original secret key can be recovered based on some analysis of the key schedule. The data complexity analysis and experiments show that only about 18 faulty ciphertexts are needed to recover the entire 128-bit secret key and about 54 faulty ciphertexts for 192/256-bit keys.

  6. Automatic differentiation algorithms in model analysis

    NARCIS (Netherlands)

    Huiskes, M.J.

    2002-01-01

    Title: Automatic differentiation algorithms in model analysis
    Author: M.J. Huiskes
    Date: 19 March, 2002

    In this thesis automatic differentiation algorithms and derivative-based methods

  7. Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.

    Science.gov (United States)

    Wan, Qi; Tang, Jing; Han, Yu; Wang, Dan

    2018-01-01

    Uveal melanoma is an aggressive cancer which has a high percentage recurrence and with a worse prognosis. Identify the potential prognostic markers of uveal melanoma may provide information for early detection of recurrence and treatment. RNA sequence data of uveal melanoma and patient clinic traits were obtained from The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by weighted gene co -expression network analysis (WGCNA) and applied to investigate the relationship underlying modules and clinic traits. Besides, functional enrichment analysis was performed on these co-expression genes from interested modules. First, using WGCNA, identified 21 co-expression modules were constructed by the 10975 genes from the 80 human uveal melanoma samples. The number of genes in these modules ranged from 42 to 5091. Found four co -expression modules significantly correlated with three clinic traits (status, recurrence and recurrence Time). Module red, and purple positively correlated with patient's life status and recurrence Time. Module green positively correlates with recurrence. The result of functional enrichment analysis showed that the module magenta was mainly enriched genetic material assemble processes, the purple module was mainly enriched in tissue homeostasis and melanosome membrane and the module red was mainly enriched metastasis of cell, suggesting its critical role in the recurrence and development of the disease. Additionally, identified the hug gene (top connectivity with other genes) in each module. The hub gene SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal melanoma. Our findings provided the framework of co-expression gene modules of uveal melanoma and identified some prognostic markers might be detection of recurrence and treatment for uveal melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Building gene co-expression networks using transcriptomics data for systems biology investigations

    DEFF Research Database (Denmark)

    Kadarmideen, Haja; Watson-Haigh, Nathan S.

    2012-01-01

    Gene co-expression networks (GCN), built using high-throughput gene expression data are fundamental aspects of systems biology. The main aims of this study were to compare two popular approaches to building and analysing GCN. We use real ovine microarray transcriptomics datasets representing four......) is connected within a network. The two GCN construction methods used were, Weighted Gene Co-expression Network Analysis (WGCNA) and Partial Correlation and Information Theory (PCIT) methods. Nodes were ranked based on their connectivity measures in each of the four different networks created by WGCNA and PCIT...... (with > 20000 genes) access to large computer clusters, particularly those with larger amounts of shared memory is recommended....

  9. Differential analysis of matrix convex functions II

    DEFF Research Database (Denmark)

    Hansen, Frank; Tomiyama, Jun

    2009-01-01

    We continue the analysis in [F. Hansen, and J. Tomiyama, Differential analysis of matrix convex functions. Linear Algebra Appl., 420:102--116, 2007] of matrix convex functions of a fixed order defined in a real interval by differential methods as opposed to the characterization in terms of divided...

  10. Selected papers on analysis and differential equations

    CERN Document Server

    Society, American Mathematical

    2010-01-01

    This volume contains translations of papers that originally appeared in the Japanese journal Sūgaku. These papers range over a variety of topics in ordinary and partial differential equations, and in analysis. Many of them are survey papers presenting new results obtained in the last few years. This volume is suitable for graduate students and research mathematicians interested in analysis and differential equations.

  11. Construction and comparison of gene co-expression networks shows complex plant immune responses

    Directory of Open Access Journals (Sweden)

    Luis Guillermo Leal

    2014-10-01

    Full Text Available Gene co-expression networks (GCNs are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA. Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses.

  12. EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.

    Science.gov (United States)

    Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki

    2014-06-01

    Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.

  13. Numerical Analysis of Partial Differential Equations

    CERN Document Server

    Lui, S H

    2011-01-01

    A balanced guide to the essential techniques for solving elliptic partial differential equations Numerical Analysis of Partial Differential Equations provides a comprehensive, self-contained treatment of the quantitative methods used to solve elliptic partial differential equations (PDEs), with a focus on the efficiency as well as the error of the presented methods. The author utilizes coverage of theoretical PDEs, along with the nu merical solution of linear systems and various examples and exercises, to supply readers with an introduction to the essential concepts in the numerical analysis

  14. Analysis of Anther Cell Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Hong [Pennsylvania State Univ., University Park, PA (United States)

    2015-01-19

    This grant supports research on genes that regulate Arabidopsis anther development. The proposed research largely concerns that functions of two key regulatory genes: SPL and DYT1, which encode two putative transcription factors, as well as genes that interact with these genes. Last year, we reported progress in preparation for ChIP analysis with SPL and DYT1, in dyt1 and ams microarray experiments and initial data analysis, in functional analysis of one of the DYT1 target gene, MYB35.

  15. Multivariate analysis of microarray data: differential expression and differential connection.

    Science.gov (United States)

    Kiiveri, Harri T

    2011-02-01

    Typical analysis of microarray data ignores the correlation between gene expression values. In this paper we present a model for microarray data which specifically allows for correlation between genes. As a result we combine gene network ideas with linear models and differential expression. We use sparse inverse covariance matrices and their associated graphical representation to capture the notion of gene networks. An important issue in using these models is the identification of the pattern of zeroes in the inverse covariance matrix. The limitations of existing methods for doing this are discussed and we provide a workable solution for determining the zero pattern. We then consider a method for estimating the parameters in the inverse covariance matrix which is suitable for very high dimensional matrices. We also show how to construct multivariate tests of hypotheses. These overall multivariate tests can be broken down into two components, the first one being similar to tests for differential expression and the second involving the connections between genes. The methods in this paper enable the extraction of a wealth of information concerning the relationships between genes which can be conveniently represented in graphical form. Differentially expressed genes can be placed in the context of the gene network and places in the gene network where unusual or interesting patterns have emerged can be identified, leading to the formulation of hypotheses for future experimentation.

  16. Multivariate analysis of microarray data: differential expression and differential connection

    Directory of Open Access Journals (Sweden)

    Kiiveri Harri T

    2011-02-01

    Full Text Available Abstract Background Typical analysis of microarray data ignores the correlation between gene expression values. In this paper we present a model for microarray data which specifically allows for correlation between genes. As a result we combine gene network ideas with linear models and differential expression. Results We use sparse inverse covariance matrices and their associated graphical representation to capture the notion of gene networks. An important issue in using these models is the identification of the pattern of zeroes in the inverse covariance matrix. The limitations of existing methods for doing this are discussed and we provide a workable solution for determining the zero pattern. We then consider a method for estimating the parameters in the inverse covariance matrix which is suitable for very high dimensional matrices. We also show how to construct multivariate tests of hypotheses. These overall multivariate tests can be broken down into two components, the first one being similar to tests for differential expression and the second involving the connections between genes. Conclusion The methods in this paper enable the extraction of a wealth of information concerning the relationships between genes which can be conveniently represented in graphical form. Differentially expressed genes can be placed in the context of the gene network and places in the gene network where unusual or interesting patterns have emerged can be identified, leading to the formulation of hypotheses for future experimentation.

  17. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Directory of Open Access Journals (Sweden)

    Yonglong Yu

    2016-04-01

    Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  18. ConGEMs: Condensed Gene Co-Expression Module Discovery Through Rule-Based Clustering and Its Application to Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Saurav Mallik

    2017-12-01

    Full Text Available For transcriptomic analysis, there are numerous microarray-based genomic data, especially those generated for cancer research. The typical analysis measures the difference between a cancer sample-group and a matched control group for each transcript or gene. Association rule mining is used to discover interesting item sets through rule-based methodology. Thus, it has advantages to find causal effect relationships between the transcripts. In this work, we introduce two new rule-based similarity measures—weighted rank-based Jaccard and Cosine measures—and then propose a novel computational framework to detect condensed gene co-expression modules ( C o n G E M s through the association rule-based learning system and the weighted similarity scores. In practice, the list of evolved condensed markers that consists of both singular and complex markers in nature depends on the corresponding condensed gene sets in either antecedent or consequent of the rules of the resultant modules. In our evaluation, these markers could be supported by literature evidence, KEGG (Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology annotations. Specifically, we preliminarily identified differentially expressed genes using an empirical Bayes test. A recently developed algorithm—RANWAR—was then utilized to determine the association rules from these genes. Based on that, we computed the integrated similarity scores of these rule-based similarity measures between each rule-pair, and the resultant scores were used for clustering to identify the co-expressed rule-modules. We applied our method to a gene expression dataset for lung squamous cell carcinoma and a genome methylation dataset for uterine cervical carcinogenesis. Our proposed module discovery method produced better results than the traditional gene-module discovery measures. In summary, our proposed rule-based method is useful for exploring biomarker modules from transcriptomic data.

  19. ConGEMs: Condensed Gene Co-Expression Module Discovery Through Rule-Based Clustering and Its Application to Carcinogenesis.

    Science.gov (United States)

    Mallik, Saurav; Zhao, Zhongming

    2017-12-28

    For transcriptomic analysis, there are numerous microarray-based genomic data, especially those generated for cancer research. The typical analysis measures the difference between a cancer sample-group and a matched control group for each transcript or gene. Association rule mining is used to discover interesting item sets through rule-based methodology. Thus, it has advantages to find causal effect relationships between the transcripts. In this work, we introduce two new rule-based similarity measures-weighted rank-based Jaccard and Cosine measures-and then propose a novel computational framework to detect condensed gene co-expression modules ( C o n G E M s) through the association rule-based learning system and the weighted similarity scores. In practice, the list of evolved condensed markers that consists of both singular and complex markers in nature depends on the corresponding condensed gene sets in either antecedent or consequent of the rules of the resultant modules. In our evaluation, these markers could be supported by literature evidence, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and Gene Ontology annotations. Specifically, we preliminarily identified differentially expressed genes using an empirical Bayes test. A recently developed algorithm-RANWAR-was then utilized to determine the association rules from these genes. Based on that, we computed the integrated similarity scores of these rule-based similarity measures between each rule-pair, and the resultant scores were used for clustering to identify the co-expressed rule-modules. We applied our method to a gene expression dataset for lung squamous cell carcinoma and a genome methylation dataset for uterine cervical carcinogenesis. Our proposed module discovery method produced better results than the traditional gene-module discovery measures. In summary, our proposed rule-based method is useful for exploring biomarker modules from transcriptomic data.

  20. VTCdb: a gene co-expression database for the crop species Vitis vinifera (grapevine).

    Science.gov (United States)

    Wong, Darren C J; Sweetman, Crystal; Drew, Damian P; Ford, Christopher M

    2013-12-16

    Gene expression datasets in model plants such as Arabidopsis have contributed to our understanding of gene function and how a single underlying biological process can be governed by a diverse network of genes. The accumulation of publicly available microarray data encompassing a wide range of biological and environmental conditions has enabled the development of additional capabilities including gene co-expression analysis (GCA). GCA is based on the understanding that genes encoding proteins involved in similar and/or related biological processes may exhibit comparable expression patterns over a range of experimental conditions, developmental stages and tissues. We present an open access database for the investigation of gene co-expression networks within the cultivated grapevine, Vitis vinifera. The new gene co-expression database, VTCdb (http://vtcdb.adelaide.edu.au/Home.aspx), offers an online platform for transcriptional regulatory inference in the cultivated grapevine. Using condition-independent and condition-dependent approaches, grapevine co-expression networks were constructed using the latest publicly available microarray datasets from diverse experimental series, utilising the Affymetrix Vitis vinifera GeneChip (16 K) and the NimbleGen Grape Whole-genome microarray chip (29 K), thus making it possible to profile approximately 29,000 genes (95% of the predicted grapevine transcriptome). Applications available with the online platform include the use of gene names, probesets, modules or biological processes to query the co-expression networks, with the option to choose between Affymetrix or Nimblegen datasets and between multiple co-expression measures. Alternatively, the user can browse existing network modules using interactive network visualisation and analysis via CytoscapeWeb. To demonstrate the utility of the database, we present examples from three fundamental biological processes (berry development, photosynthesis and flavonoid biosynthesis

  1. Co-expression Network Approach to Studying the Effects of Botulinum Neurotoxin-A.

    Science.gov (United States)

    Mukund, Kavitha; Ward, Samuel R; Lieber, Richard L; Subramaniam, Shankar

    2017-10-16

    Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A. Functional analysis revealed enrichment of group 1 with metabolism; group 5 with contradictory functions of atrophy and cellular recovery; and groups 2 and 3 with extracellular matrix (ECM) and non-fast fiber isoforms. Topological positioning of two highly ranked, significantly expressed genes- Dclk1 and Ostalpha within group 5 suggested possible mechanistic roles in recovery from BoNT-A induced atrophy. Phenotypic correlations of groups with titin and myosin protein content further emphasized the effect of BoNT-A on the sarcomeric contraction machinery in early phase of chemodenervation. In summary, our approach revealed a hierarchical functional response to BoNT-A induced paralysis with early metabolic and later ECM responses and identified putative biomarkers associated with chemodenervation. Additionally, our results provide an unbiased validation of the response documented in our previous workBotulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules

  2. Inferring the transcriptional landscape of bovine skeletal muscle by integrating co-expression networks.

    Directory of Open Access Journals (Sweden)

    Nicholas J Hudson

    Full Text Available BACKGROUND: Despite modern technologies and novel computational approaches, decoding causal transcriptional regulation remains challenging. This is particularly true for less well studied organisms and when only gene expression data is available. In muscle a small number of well characterised transcription factors are proposed to regulate development. Therefore, muscle appears to be a tractable system for proposing new computational approaches. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a simple algorithm that asks "which transcriptional regulator has the highest average absolute co-expression correlation to the genes in a co-expression module?" It correctly infers a number of known causal regulators of fundamental biological processes, including cell cycle activity (E2F1, glycolysis (HLF, mitochondrial transcription (TFB2M, adipogenesis (PIAS1, neuronal development (TLX3, immune function (IRF1 and vasculogenesis (SOX17, within a skeletal muscle context. However, none of the canonical pro-myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6 and MEF2C were linked to muscle structural gene expression modules. Co-expression values were computed using developing bovine muscle from 60 days post conception (early foetal to 30 months post natal (adulthood for two breeds of cattle, in addition to a nutritional comparison with a third breed. A number of transcriptional landscapes were constructed and integrated into an always correlated landscape. One notable feature was a 'metabolic axis' formed from glycolysis genes at one end, nuclear-encoded mitochondrial protein genes at the other, and centrally tethered by mitochondrially-encoded mitochondrial protein genes. CONCLUSIONS/SIGNIFICANCE: The new module-to-regulator algorithm complements our recently described Regulatory Impact Factor analysis. Together with a simple examination of a co-expression module's contents, these three gene expression approaches are starting to illuminate the in vivo

  3. Large clusters of co-expressed genes in the Drosophila genome.

    Science.gov (United States)

    Boutanaev, Alexander M; Kalmykova, Alla I; Shevelyov, Yuri Y; Nurminsky, Dmitry I

    2002-12-12

    Clustering of co-expressed, non-homologous genes on chromosomes implies their co-regulation. In lower eukaryotes, co-expressed genes are often found in pairs. Clustering of genes that share aspects of transcriptional regulation has also been reported in higher eukaryotes. To advance our understanding of the mode of coordinated gene regulation in multicellular organisms, we performed a genome-wide analysis of the chromosomal distribution of co-expressed genes in Drosophila. We identified a total of 1,661 testes-specific genes, one-third of which are clustered on chromosomes. The number of clusters of three or more genes is much higher than expected by chance. We observed a similar trend for genes upregulated in the embryo and in the adult head, although the expression pattern of individual genes cannot be predicted on the basis of chromosomal position alone. Our data suggest that the prevalent mechanism of transcriptional co-regulation in higher eukaryotes operates with extensive chromatin domains that comprise multiple genes.

  4. Dynamic sporulation gene co-expression networks for Bacillus subtilis 168 and the food-borne isolate Bacillus amyloliquefaciens: a transcriptomic model.

    Science.gov (United States)

    Omony, Jimmy; de Jong, Anne; Krawczyk, Antonina O; Eijlander, Robyn T; Kuipers, Oscar P

    2018-02-09

    Sporulation is a survival strategy, adapted by bacterial cells in response to harsh environmental adversities. The adaptation potential differs between strains and the variations may arise from differences in gene regulation. Gene networks are a valuable way of studying such regulation processes and establishing associations between genes. We reconstructed and compared sporulation gene co-expression networks (GCNs) of the model laboratory strain Bacillus subtilis 168 and the food-borne industrial isolate Bacillus amyloliquefaciens. Transcriptome data obtained from samples of six stages during the sporulation process were used for network inference. Subsequently, a gene set enrichment analysis was performed to compare the reconstructed GCNs of B. subtilis 168 and B. amyloliquefaciens with respect to biological functions, which showed the enriched modules with coherent functional groups associated with sporulation. On basis of the GCNs and time-evolution of differentially expressed genes, we could identify novel candidate genes strongly associated with sporulation in B. subtilis 168 and B. amyloliquefaciens. The GCNs offer a framework for exploring transcription factors, their targets, and co-expressed genes during sporulation. Furthermore, the methodology described here can conveniently be applied to other species or biological processes.

  5. Enforcing Co-expression Within a Brain-Imaging Genomics Regression Framework.

    Science.gov (United States)

    Zille, Pascal; Calhoun, Vince D; Wang, Yu-Ping

    2017-06-28

    Among the challenges arising in brain imaging genetic studies, estimating the potential links between neurological and genetic variability within a population is key. In this work, we propose a multivariate, multimodal formulation for variable selection that leverages co-expression patterns across various data modalities. Our approach is based on an intuitive combination of two widely used statistical models: sparse regression and canonical correlation analysis (CCA). While the former seeks multivariate linear relationships between a given phenotype and associated observations, the latter searches to extract co-expression patterns between sets of variables belonging to different modalities. In the following, we propose to rely on a 'CCA-type' formulation in order to regularize the classical multimodal sparse regression problem (essentially incorporating both CCA and regression models within a unified formulation). The underlying motivation is to extract discriminative variables that are also co-expressed across modalities. We first show that the simplest formulation of such model can be expressed as a special case of collaborative learning methods. After discussing its limitation, we propose an extended, more flexible formulation, and introduce a simple and efficient alternating minimization algorithm to solve the associated optimization problem.We explore the parameter space and provide some guidelines regarding parameter selection. Both the original and extended versions are then compared on a simple toy dataset and a more advanced simulated imaging genomics dataset in order to illustrate the benefits of the latter. Finally, we validate the proposed formulation using single nucleotide polymorphisms (SNP) data and functional magnetic resonance imaging (fMRI) data from a population of adolescents (n = 362 subjects, age 16.9 ± 1.9 years from the Philadelphia Neurodevelopmental Cohort) for the study of learning ability. Furthermore, we carry out a significance

  6. Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

    Science.gov (United States)

    Pabba, Mohan; Scifo, Enzo; Kapadia, Fenika; Nikolova, Yuliya S; Ma, Tianzhou; Mechawar, Naguib; Tseng, George C; Sibille, Etienne

    2017-10-01

    The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Improvisation and co-expression in explorative digital music systems

    DEFF Research Database (Denmark)

    Hansen, Anne-Marie Skriver

    relationships. The benefit of the digitally networked electronic musical instruments is that particular patterns of co-expression can be found and mediated by the music system (that also contains all individual instruments) in ways that make players aware of their mutual play and perhaps will encourage players...... other when they are given a number of creative restrictions in the sonic/musical material that they interact with. The benefit with digital musical instruments is that non-musicians and novices can get access to limited musical material that they are immediately able to master without any musical...... be developed in future designs. The Wacom® pen tablet, a simple drawing interface, was turned into an array of digital musical instruments in order to investigate the benefit of networked musical instruments in the context of the genre of casual games. Through qualitative and quantitative studies of player...

  8. Effects of threshold on the topology of gene co-expression networks.

    Science.gov (United States)

    Couto, Cynthia Martins Villar; Comin, César Henrique; Costa, Luciano da Fontoura

    2017-09-26

    Several developments regarding the analysis of gene co-expression profiles using complex network theory have been reported recently. Such approaches usually start with the construction of an unweighted gene co-expression network, therefore requiring the selection of a suitable threshold defining which pairs of vertices will be connected. We aimed at addressing such an important problem by suggesting and comparing five different approaches for threshold selection. Each of the methods considers a respective biologically-motivated criterion for electing a potentially suitable threshold. A set of 21 microarray experiments from different biological groups was used to investigate the effect of applying the five proposed criteria to several biological situations. For each experiment, we used the Pearson correlation coefficient to measure the relationship between each gene pair, and the resulting weight matrices were thresholded considering several values, generating respective adjacency matrices (co-expression networks). Each of the five proposed criteria was then applied in order to select the respective threshold value. The effects of these thresholding approaches on the topology of the resulting networks were compared by using several measurements, and we verified that, depending on the database, the impact on the topological properties can be large. However, a group of databases was verified to be similarly affected by most of the considered criteria. Based on such results, it can be suggested that when the generated networks present similar measurements, the thresholding method can be chosen with greater freedom. If the generated networks are markedly different, the thresholding method that better suits the interests of each specific research study represents a reasonable choice.

  9. Network statistics of genetically-driven gene co-expression modules in mouse crosses

    Directory of Open Access Journals (Sweden)

    Marie-Pier eScott-Boyer

    2013-12-01

    Full Text Available In biology, networks are used in different contexts as ways to represent relationships between entities, such as for instance interactions between genes, proteins or metabolites. Despite progress in the analysis of such networks and their potential to better understand the collective impact of genes on complex traits, one remaining challenge is to establish the biologic validity of gene co-expression networks and to determine what governs their organization. We used WGCNA to construct and analyze seven gene expression datasets from several tissues of mouse recombinant inbred strains (RIS. For six out of the 7 networks, we found that linkage to module QTLs (mQTLs could be established for 29.3% of gene co-expression modules detected in the several mouse RIS. For about 74.6% of such genetically-linked modules, the mQTL was on the same chromosome as the one contributing most genes to the module, with genes originating from that chromosome showing higher connectivity than other genes in the modules. Such modules (that we considered as genetically-driven had network statistic properties (density, centralization and heterogeneity that set them apart from other modules in the network. Altogether, a sizeable portion of gene co-expression modules detected in mouse RIS panels had genetic determinants as their main organizing principle. In addition to providing a biologic interpretation validation for these modules, these genetic determinants imparted on them particular properties that set them apart from other modules in the network, to the point that they can be predicted to a large extent on the basis of their network statistics.

  10. Numerical analysis of systems of ordinary and stochastic differential equations

    CERN Document Server

    Artemiev, S S

    1997-01-01

    This text deals with numerical analysis of systems of both ordinary and stochastic differential equations. It covers numerical solution problems of the Cauchy problem for stiff ordinary differential equations (ODE) systems by Rosenbrock-type methods (RTMs).

  11. Uncovering co-expression gene network modules regulating fruit acidity in diverse apples.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Zhong, Gan-Yuan; Xu, Kenong

    2015-08-16

    Acidity is a major contributor to fruit quality. Several organic acids are present in apple fruit, but malic acid is predominant and determines fruit acidity. The trait is largely controlled by the Malic acid (Ma) locus, underpinning which Ma1 that putatively encodes a vacuolar aluminum-activated malate transporter1 (ALMT1)-like protein is a strong candidate gene. We hypothesize that fruit acidity is governed by a gene network in which Ma1 is key member. The goal of this study is to identify the gene network and the potential mechanisms through which the network operates. Guided by Ma1, we analyzed the transcriptomes of mature fruit of contrasting acidity from six apple accessions of genotype Ma_ (MaMa or Mama) and four of mama using RNA-seq and identified 1301 fruit acidity associated genes, among which 18 were most significant acidity genes (MSAGs). Network inferring using weighted gene co-expression network analysis (WGCNA) revealed five co-expression gene network modules of significant (P acidity. Overall, this study provides important insight into the Ma1-mediated gene network controlling acidity in mature apple fruit of diverse genetic background.

  12. Extracting gene expression patterns and identifying co-expressed genes from microarray data reveals biologically responsive processes

    Directory of Open Access Journals (Sweden)

    Paules Richard S

    2007-11-01

    Full Text Available Abstract Background A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions. Results Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and L1 starvation in C. elegans and after ultraviolet (UV or ionizing radiation (IR-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying

  13. Differential-thermal analysis of irradiated lignite

    International Nuclear Information System (INIS)

    Chichek, F.; Eyubova, N.

    2006-01-01

    Full text: In this theme our purpose is to explain thermo-differential analysis of lignites irradiated. During experiment Caraman Ermenek (washed), Caraman Ermenek (crude), Nevshehir (crude), Slopi (crude), Trakya Harman (washed) lignite coals were used. Five of five kinds of coal samples with 3mm and 1gr of each sample were obtained. Then they were filled into the Tubes after having dried total 25 samples with 1 gr at 1000 degrees temperature for one hour. Air in the tubes was pumped out and closed. Coal samples in vacuum medium were irradiated by gamma rays of Co60 at 5.5 kGy, 19.2 kGy, 65.7 kGy, 169.6 kGy, 411.2 kGy doses to the normal conditions. Then differential thermal analysis was carried out both in original and the samples irradiated. Argon gas was used to make inert medium in the camera. T=200-8500 degrees temperature was selected. At the experiment done from 1000-1300 degrees temperatures too great endothermic reaction pick was begun to form by being observed thermal changings. At 3000-4200 degrees temperature exothermic reaction picks and at 7000 degrees parallel exothermic reaction picks were observed. Initial endothermic and exothermic reaction picks in five lignite samples were observed like a sharp curve. At the end coal irradiated samples were compared with original coal samples. At the result of experiment it was revealed that in comparison with original coal samples coal samples irradiated form exothermic and endothermic curves at very reaction pick and temperature intervals of these pick were large. Besides loss of weight was observed to begin at low temperatures in samples irradiated and especially momentary weight loss at some heats in the rang of known temperatures was observed in the coal Slopi contain in bitumen. Because of heat the weigh loss in the non irradiated samples forms parabolic curve and because of heat the weight loss in the samples irradiated forms stepped curves. It has shown that the coal irradiated can be easily departed by

  14. Applying homotopy analysis method for solving differential-difference equation

    International Nuclear Information System (INIS)

    Wang Zhen; Zou Li; Zhang Hongqing

    2007-01-01

    In this Letter, we apply the homotopy analysis method to solving the differential-difference equations. A simple but typical example is applied to illustrate the validity and the great potential of the generalized homotopy analysis method in solving differential-difference equation. Comparisons are made between the results of the proposed method and exact solutions. The results show that the homotopy analysis method is an attractive method in solving the differential-difference equations

  15. Stability analysis of impulsive functional differential equations

    CERN Document Server

    Stamova, Ivanka

    2009-01-01

    This book is devoted to impulsive functional differential equations which are a natural generalization of impulsive ordinary differential equations (without delay) and of functional differential equations (without impulses). At the present time the qualitative theory of such equationsis under rapid development. After a presentation of the fundamental theory of existence, uniqueness and continuability of solutions, a systematic development of stability theory for that class of problems is given which makes the book unique. It addresses to a wide audience such as mathematicians, applied research

  16. Selected papers on analysis and differential equations

    CERN Document Server

    Nomizu, Katsumi

    2003-01-01

    This volume contains translations of papers that originally appeared in the Japanese journal, Sugaku. The papers range over a variety of topics, including nonlinear partial differential equations, C^*-algebras, and Schrödinger operators.

  17. Differential-thermal analysis of irradiated lignite

    International Nuclear Information System (INIS)

    Chichek, F; Eyubova, N.

    2006-01-01

    Full text: In this theme our purpose is to explain thermo-differential analysis of lignite's irradiated. During experiment Caraman Ermenek (washed), Caraman Ermenek (crude), Nevshehir (crude), Slopi (crude), Trakya Harman (washed) lignite coals were used. Five of five kinds of coal samples with 3mm and 1 gr of each sample were obtained. Then they were filled into the Tubes after having dried total 25 samples with 1 gr at 1000C temperature for one hour. Air in the tubes was pumped out and closed. Coal samples in vacuum medium were irradiated by gamma rays of Co-60 at 5.5 kGy, 19.2 kGy, 65.7 kGy, 169.6 kGy, 411.2 kGy, doses to the normal conditions. At the end coal irradiated samples were compared with original coal samples. At the result of experiment it was revealed that in comparison with original coal samples coal samples irradiated from exothermic and endothermic curves at very reaction pick and temperature intervals of these pick were large. Besides loss of weight was observed to begin at low temperatures in samples irradiated and especially momentary weight loss at some heats in the rang of known temperatures was observed in the coal Slopi contain in bitumen. Because of heat the weight loss in the non irradiated samples forms parabolic curve and because of heat the weight loss in the samples irradiated forms stepped curves. It was shown that the coal irradiated can be easily departed by heat because of the chemical structure in comparison the original one.

  18. Sensitivity analysis and design optimization through automatic differentiation

    International Nuclear Information System (INIS)

    Hovland, Paul D; Norris, Boyana; Strout, Michelle Mills; Bhowmick, Sanjukta; Utke, Jean

    2005-01-01

    Automatic differentiation is a technique for transforming a program or subprogram that computes a function, including arbitrarily complex simulation codes, into one that computes the derivatives of that function. We describe the implementation and application of automatic differentiation tools. We highlight recent advances in the combinatorial algorithms and compiler technology that underlie successful implementation of automatic differentiation tools. We discuss applications of automatic differentiation in design optimization and sensitivity analysis. We also describe ongoing research in the design of language-independent source transformation infrastructures for automatic differentiation algorithms

  19. Asymptotic analysis for functional stochastic differential equations

    CERN Document Server

    Bao, Jianhai; Yuan, Chenggui

    2016-01-01

    This brief treats dynamical systems that involve delays and random disturbances. The study is motivated by a wide variety of systems in real life in which random noise has to be taken into consideration and the effect of delays cannot be ignored. Concentrating on such systems that are described by functional stochastic differential equations, this work focuses on the study of large time behavior, in particular, ergodicity. This brief is written for probabilists, applied mathematicians, engineers, and scientists who need to use delay systems and functional stochastic differential equations in their work. Selected topics from the brief can also be used in a graduate level topics course in probability and stochastic processes.

  20. An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks.

    Science.gov (United States)

    Botía, Juan A; Vandrovcova, Jana; Forabosco, Paola; Guelfi, Sebastian; D'Sa, Karishma; Hardy, John; Lewis, Cathryn M; Ryten, Mina; Weale, Michael E

    2017-04-12

    Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.

  1. Decomposition analysis of differential dose volume histograms

    International Nuclear Information System (INIS)

    Heuvel, Frank van den

    2006-01-01

    Dose volume histograms are a common tool to assess the value of a treatment plan for various forms of radiation therapy treatment. The purpose of this work is to introduce, validate, and apply a set of tools to analyze differential dose volume histograms by decomposing them into physically and clinically meaningful normal distributions. A weighted sum of the decomposed normal distributions (e.g., weighted dose) is proposed as a new measure of target dose, rather than the more unstable point dose. The method and its theory are presented and validated using simulated distributions. Additional validation is performed by analyzing simple four field box techniques encompassing a predefined target, using different treatment energies inside a water phantom. Furthermore, two clinical situations are analyzed using this methodology to illustrate practical usefulness. A comparison of a treatment plan for a breast patient using a tangential field setup with wedges is compared to a comparable geometry using dose compensators. Finally, a normal tissue complication probability (NTCP) calculation is refined using this decomposition. The NTCP calculation is performed on a liver as organ at risk in a treatment of a mesothelioma patient with involvement of the right lung. The comparison of the wedged breast treatment versus the compensator technique yields comparable classical dose parameters (e.g., conformity index ≅1 and equal dose at the ICRU dose point). The methodology proposed here shows a 4% difference in weighted dose outlining the difference in treatment using a single parameter instead of at least two in a classical analysis (e.g., mean dose, and maximal dose, or total dose variance). NTCP-calculations for the mesothelioma case are generated automatically and show a 3% decrease with respect to the classical calculation. The decrease is slightly dependant on the fractionation and on the α/β-value utilized. In conclusion, this method is able to distinguish clinically

  2. Continuous nowhere differentiable functions the monsters of analysis

    CERN Document Server

    Jarnicki, Marek

    2015-01-01

    This book covers the construction, analysis, and theory of continuous nowhere differentiable functions, comprehensively and accessibly. After illuminating the significance of the subject through an overview of its history, the reader is introduced to the sophisticated toolkit of ideas and tricks used to study the explicit continuous nowhere differentiable functions of Weierstrass, Takagi–van der Waerden, Bolzano, and others. Modern tools of functional analysis, measure theory, and Fourier analysis are applied to examine the generic nature of continuous nowhere differentiable functions, as well as linear structures within the (nonlinear) space of continuous nowhere differentiable functions. To round out the presentation, advanced techniques from several areas of mathematics are brought together to give a state-of-the-art analysis of Riemann’s continuous, and purportedly nowhere differentiable, function. For the reader’s benefit, claims requiring elaboration, and open problems, are clearly indicated. An a...

  3. Tensor analysis and elementary differential geometry for physicists and engineers

    CERN Document Server

    Nguyen-Schäfer, Hung

    2017-01-01

    This book comprehensively presents topics, such as Dirac notation, tensor analysis, elementary differential geometry of moving surfaces, and k-differential forms. Additionally, two new chapters of Cartan differential forms and Dirac and tensor notations in quantum mechanics are added to this second edition. The reader is provided with hands-on calculations and worked-out examples at which he will learn how to handle the bra-ket notation, tensors, differential geometry, and differential forms; and to apply them to the physical and engineering world. Many methods and applications are given in CFD, continuum mechanics, electrodynamics in special relativity, cosmology in the Minkowski four-dimensional spacetime, and relativistic and non-relativistic quantum mechanics. Tensors, differential geometry, differential forms, and Dirac notation are very useful advanced mathematical tools in many fields of modern physics and computational engineering. They are involved in special and general relativity physics, quantum m...

  4. Estimation of the proteomic cancer co-expression sub networks by using association estimators.

    Directory of Open Access Journals (Sweden)

    Cihat Erdoğan

    Full Text Available In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA. Correlation and mutual information (MI based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators' performance, a multi-layer data integration platform on gene-disease associations (DisGeNET and the Molecular Signatures Database (MSigDB was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink and 64% for Schurmann-Grassberger (SG association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists.

  5. Differential analysis of matrix convex functions

    DEFF Research Database (Denmark)

    Hansen, Frank; Tomiyama, Jun

    2007-01-01

    We analyze matrix convex functions of a fixed order defined in a real interval by differential methods as opposed to the characterization in terms of divided differences given by Kraus [F. Kraus, Über konvekse Matrixfunktionen, Math. Z. 41 (1936) 18-42]. We obtain for each order conditions for ma...

  6. Differential equation analysis in biomedical science and engineering ordinary differential equation applications with R

    CERN Document Server

    Schiesser, William E

    2014-01-01

    Features a solid foundation of mathematical and computational tools to formulate and solve real-world ODE problems across various fields With a step-by-step approach to solving ordinary differential equations (ODEs), Differential Equation Analysis in Biomedical Science and Engineering: Ordinary Differential Equation Applications with R successfully applies computational techniques for solving real-worldODE problems that are found in a variety of fields, including chemistry, physics, biology,and physiology. The book provides readers with the necessary knowledge to reproduce andextend the comp

  7. Differential equation analysis in biomedical science and engineering partial differential equation applications with R

    CERN Document Server

    Schiesser, William E

    2014-01-01

    Features a solid foundation of mathematical and computational tools to formulate and solve real-world PDE problems across various fields With a step-by-step approach to solving partial differential equations (PDEs), Differential Equation Analysis in Biomedical Science and Engineering: Partial Differential Equation Applications with R successfully applies computational techniques for solving real-world PDE problems that are found in a variety of fields, including chemistry, physics, biology, and physiology. The book provides readers with the necessary knowledge to reproduce and extend the com

  8. Transcriptomic Analysis of Flower Bud Differentiation in Magnolia sinostellata

    Directory of Open Access Journals (Sweden)

    Lijie Fan

    2018-04-01

    Full Text Available Magnolias are widely cultivated for their beautiful flowers, but despite their popularity, the molecular mechanisms regulating flower bud differentiation have not been elucidated. Here, we used paraffin sections and RNA-seq to study the process of flower bud differentiation in Magnolia sinostellata. Flower bud development occurred between 28 April and 30 May 2017 and was divided into five stages: undifferentiated, early flower bud differentiation, petal primordium differentiation, stamen primordium differentiation, and pistil primordium differentiation. A total of 52,441 expressed genes were identified, of which 11,592 were significantly differentially expressed in the five bud development stages. Of these, 82 genes were involved in the flowering. In addition, MADS-box and AP2 family genes play critical roles in the formation of flower organs and 20 differentially expressed genes associated with flower bud differentiation were identified in M. sinostellata. A qRT-PCR analysis verified that the MADS-box and AP2 family genes were expressed at high levels during flower bud differentiation. Consequently, this study provides a theoretical basis for the genetic regulation of flowering in M. sinostellata, which lays a foundation for further research into flowering genes and may facilitate the development of new cultivars.

  9. Noise Analysis of Single-Ended Input Differential Amplifier using Stochastic Differential Equation

    OpenAIRE

    Tarun Kumar Rawat; Abhirup Lahiri; Ashish Gupta

    2008-01-01

    In this paper, we analyze the effect of noise in a single- ended input differential amplifier working at high frequencies. Both extrinsic and intrinsic noise are analyzed using time domain method employing techniques from stochastic calculus. Stochastic differential equations are used to obtain autocorrelation functions of the output noise voltage and other solution statistics like mean and variance. The analysis leads to important design implications and suggests changes in the device parame...

  10. Long SAGE analysis of genes differentially expressed in the midgut ...

    African Journals Online (AJOL)

    Long SAGE analysis of genes differentially expressed in the midgut and silk gland between the sexes of the silkwormBombyx mori. Liping Gan, Ying Wang, Jian Xi, Yanshan Niu, Hongyou Qin, Yanghu Sima, Shiqing Xu ...

  11. PC analysis of stochastic differential equations driven by Wiener noise

    KAUST Repository

    Le Maitre, Olivier; Knio, Omar

    2015-01-01

    A polynomial chaos (PC) analysis with stochastic expansion coefficients is proposed for stochastic differential equations driven by additive or multiplicative Wiener noise. It is shown that for this setting, a Galerkin formalism naturally leads

  12. International conference Fourier Analysis and Pseudo-Differential Operators

    CERN Document Server

    Turunen, Ville; Fourier Analysis : Pseudo-differential Operators, Time-Frequency Analysis and Partial Differential Equations

    2014-01-01

    This book is devoted to the broad field of Fourier analysis and its applications to several areas of mathematics, including problems in the theory of pseudo-differential operators, partial differential equations, and time-frequency analysis. This collection of 20 refereed articles is based on selected talks given at the international conference “Fourier Analysis and Pseudo-Differential Operators,” June 25–30, 2012, at Aalto University, Finland, and presents the latest advances in the field. The conference was a satellite meeting of the 6th European Congress of Mathematics, which took place in Krakow in July 2012; it was also the 6th meeting in the series “Fourier Analysis and Partial Differential Equations.”

  13. Dynamic data analysis modeling data with differential equations

    CERN Document Server

    Ramsay, James

    2017-01-01

    This text focuses on the use of smoothing methods for developing and estimating differential equations following recent developments in functional data analysis and building on techniques described in Ramsay and Silverman (2005) Functional Data Analysis. The central concept of a dynamical system as a buffer that translates sudden changes in input into smooth controlled output responses has led to applications of previously analyzed data, opening up entirely new opportunities for dynamical systems. The technical level has been kept low so that those with little or no exposure to differential equations as modeling objects can be brought into this data analysis landscape. There are already many texts on the mathematical properties of ordinary differential equations, or dynamic models, and there is a large literature distributed over many fields on models for real world processes consisting of differential equations. However, a researcher interested in fitting such a model to data, or a statistician interested in...

  14. Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

    Science.gov (United States)

    Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

    2015-09-01

    Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Genes and co-expression modules common to drought and bacterial stress responses in Arabidopsis and rice.

    Directory of Open Access Journals (Sweden)

    Rafi Shaik

    Full Text Available Plants are simultaneously exposed to multiple stresses resulting in enormous changes in the molecular landscape within the cell. Identification and characterization of the synergistic and antagonistic components of stress response mechanisms contributing to the cross talk between stresses is of high priority to explore and enhance multiple stress responses. To this end, we performed meta-analysis of drought (abiotic, bacterial (biotic stress response in rice and Arabidopsis by analyzing a total of 386 microarray samples belonging to 20 microarray studies and identified approximately 3100 and 900 DEGs in rice and Arabidopsis, respectively. About 38.5% (1214 and 28.7% (272 DEGs were common to drought and bacterial stresses in rice and Arabidopsis, respectively. A majority of these common DEGs showed conserved expression status in both stresses. Gene ontology enrichment analysis clearly demarcated the response and regulation of various plant hormones and related biological processes. Fatty acid metabolism and biosynthesis of alkaloids were upregulated and, nitrogen metabolism and photosynthesis was downregulated in both stress conditions. WRKY transcription family genes were highly enriched in all upregulated gene sets while 'CO-like' TF family showed inverse relationship of expression between drought and bacterial stresses. Weighted gene co-expression network analysis divided DEG sets into multiple modules that show high co-expression and identified stress specific hub genes with high connectivity. Detection of consensus modules based on DEGs common to drought and bacterial stress revealed 9 and 4 modules in rice and Arabidopsis, respectively, with conserved and reversed co-expression patterns.

  16. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  17. Co-Expression of Bmi-1 and Podoplanin Predicts Overall Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Radio(chemo)therapy

    International Nuclear Information System (INIS)

    Vormittag, Laurenz; Thurnher, Dietmar; Geleff, Silvana; Pammer, Johannes; Heiduschka, Gregor; Brunner, Markus; Grasl, Matthaeus Ch.; Erovic, Boban M.

    2009-01-01

    Purpose: This study was conducted to determine the expression of Bmi-1 and podoplanin in healthy oral mucosa and in untreated tumor tissues samples of patients with squamous cell carcinomas of the head and neck. All patients were treated by primary radio(chemo)therapy. Methods and Materials: The expression of Bmi-1 and podoplanin was immunohistochemically evaluated in 12 normal oral mucosa and 63 tumor specimens and correlated with patients' clinical data. Results: In healthy mucosa expression of Bmi-1 and podoplanin was restricted to the basal cell layer. Expression of both proteins was found in 79% and 86% of our tumor samples, respectively. In 17 and 8 samples, Bmi-1 and podoplanin were co-expressed at the invasive border or diffuse in the bulk of the tumor, respectively. Univariate analysis showed that the co-expression of Bmi-1 and podoplanin correlated to decreased overall survival (p = 0.044). Moreover, multivariate testing identified high expression of podoplanin (p = 0.044), co-expression of Bmi-1 and podoplanin (p = 0.007) and lack of response to therapy (p < 0.0001) as predictors of shortened overall survival in patients treated with primary radio(chemo)therapy. Conclusions: Bmi-1 and podoplanin are expressed at the invasive front of squamous cell carcinomas of the head and neck. Co-expression of Bmi-1 and podoplanin predicts significantly overall survival of patients treated with primary radio(chemo)therapy

  18. Discovery of cis-elements between sorghum and rice using co-expression and evolutionary conservation

    Directory of Open Access Journals (Sweden)

    Haberer Georg

    2009-06-01

    Full Text Available Abstract Background The spatiotemporal regulation of gene expression largely depends on the presence and absence of cis-regulatory sites in the promoter. In the economically highly important grass family, our knowledge of transcription factor binding sites and transcriptional networks is still very limited. With the completion of the sorghum genome and the available rice genome sequence, comparative promoter analyses now allow genome-scale detection of conserved cis-elements. Results In this study, we identified thousands of phylogenetic footprints conserved between orthologous rice and sorghum upstream regions that are supported by co-expression information derived from three different rice expression data sets. In a complementary approach, cis-motifs were discovered by their highly conserved co-occurrence in syntenic promoter pairs. Sequence conservation and matches to known plant motifs support our findings. Expression similarities of gene pairs positively correlate with the number of motifs that are shared by gene pairs and corroborate the importance of similar promoter architectures for concerted regulation. This strongly suggests that these motifs function in the regulation of transcript levels in rice and, presumably also in sorghum. Conclusion Our work provides the first large-scale collection of cis-elements for rice and sorghum and can serve as a paradigm for cis-element analysis through comparative genomics in grasses in general.

  19. Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

    Science.gov (United States)

    Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

    2000-01-01

    Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.

  20. Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

    Science.gov (United States)

    Hulsman, Marc; Lelieveldt, Boudewijn P. F.; de Ridder, Jeroen; Reinders, Marcel

    2015-01-01

    The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale). PMID:25965262

  1. Proteomic analysis of osteogenic differentiation of dental follicle precursor cells

    DEFF Research Database (Denmark)

    Morsczeck, Christian; Petersen, Jørgen; Völlner, Florian

    2009-01-01

    of differentiation. In the present study we applied 2-DE combined with capillary-LC-MS/MS analysis to profile differentially regulated proteins upon differentiation of dental follicle precursor cells (DFPCs). Out of 115 differentially regulated proteins, glutamine synthetase, lysosomal proteinase cathepsin B....... The bioinformatic analyses suggest that proteins associated with cell cycle progression and protein metabolism were down-regulated and proteins involved in catabolism, cell motility and biological quality were up-regulated. These results display the general physiological state of DFPCs before and after osteogenic...... proteins, plastin 3 T-isoform, beta-actin, superoxide dismutases, and transgelin were found to be highly up-regulated, whereas cofilin-1, pro-alpha 1 collagen, destrin, prolyl 4-hydrolase and dihydrolipoamide dehydrogenase were found to be highly down-regulated. The group of up-regulated proteins...

  2. Tensor and vector analysis with applications to differential geometry

    CERN Document Server

    Springer, C E

    2012-01-01

    Concise and user-friendly, this college-level text assumes only a knowledge of basic calculus in its elementary and gradual development of tensor theory. The introductory approach bridges the gap between mere manipulation and a genuine understanding of an important aspect of both pure and applied mathematics.Beginning with a consideration of coordinate transformations and mappings, the treatment examines loci in three-space, transformation of coordinates in space and differentiation, tensor algebra and analysis, and vector analysis and algebra. Additional topics include differentiation of vect

  3. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    Science.gov (United States)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  4. A co-expression gene network associated with developmental regulation of apple fruit acidity.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Xu, Kenong

    2015-08-01

    Apple fruit acidity, which affects the fruit's overall taste and flavor to a large extent, is primarily determined by the concentration of malic acid. Previous studies demonstrated that the major QTL malic acid (Ma) on chromosome 16 is largely responsible for fruit acidity variations in apple. Recent advances suggested that a natural mutation that gives rise to a premature stop codon in one of the two aluminum-activated malate transporter (ALMT)-like genes (called Ma1) is the genetic causal element underlying Ma. However, the natural mutation does not explain the developmental changes of fruit malate levels in a given genotype. Using RNA-seq data from the fruit of 'Golden Delicious' taken at 14 developmental stages from 1 week after full-bloom (WAF01) to harvest (WAF20), we characterized their transcriptomes in groups of high (12.2 ± 1.6 mg/g fw, WAF03-WAF08), mid (7.4 ± 0.5 mg/g fw, WAF01-WAF02 and WAF10-WAF14) and low (5.4 ± 0.4 mg/g fw, WAF16-WAF20) malate concentrations. Detailed analyses showed that a set of 3,066 genes (including Ma1) were expressed not only differentially (P FDR < 0.05) between the high and low malate groups (or between the early and late developmental stages) but also in significant (P < 0.05) correlation with malate concentrations. The 3,066 genes fell in 648 MapMan (sub-) bins or functional classes, and 19 of them were significantly (P FDR < 0.05) co-enriched or co-suppressed in a malate dependent manner. Network inferring using the 363 genes encompassed in the 19 (sub-) bins, identified a major co-expression network of 239 genes. Since the 239 genes were also differentially expressed between the early (WAF03-WAF08) and late (WAF16-WAF20) developmental stages, the major network was considered to be associated with developmental regulation of apple fruit acidity in 'Golden Delicious'.

  5. Identification of estrogen receptor dimer selective ligands reveals growth-inhibitory effects on cells that co-express ERα and ERβ.

    Directory of Open Access Journals (Sweden)

    Emily Powell

    Full Text Available Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ.

  6. High Order Differential Frequency Hopping: Design and Analysis

    Directory of Open Access Journals (Sweden)

    Yong Li

    2015-01-01

    Full Text Available This paper considers spectrally efficient differential frequency hopping (DFH system design. Relying on time-frequency diversity over large spectrum and high speed frequency hopping, DFH systems are robust against hostile jamming interference. However, the spectral efficiency of conventional DFH systems is very low due to only using the frequency of each channel. To improve the system capacity, in this paper, we propose an innovative high order differential frequency hopping (HODFH scheme. Unlike in traditional DFH where the message is carried by the frequency relationship between the adjacent hops using one order differential coding, in HODFH, the message is carried by the frequency and phase relationship using two-order or higher order differential coding. As a result, system efficiency is increased significantly since the additional information transmission is achieved by the higher order differential coding at no extra cost on either bandwidth or power. Quantitative performance analysis on the proposed scheme demonstrates that transmission through the frequency and phase relationship using two-order or higher order differential coding essentially introduces another dimension to the signal space, and the corresponding coding gain can increase the system efficiency.

  7. Variational analysis and generalized differentiation I basic theory

    CERN Document Server

    Mordukhovich, Boris S

    2006-01-01

    Contains a study of the basic concepts and principles of variational analysis and generalized differentiation in both finite-dimensional and infinite-dimensional spaces. This title presents many applications to problems in optimization, equilibria, stability and sensitivity, control theory, economics, mechanics, and more.

  8. Function spaces and partial differential equations volume 2 : contemporary analysis

    CERN Document Server

    Taheri, Ali

    2015-01-01

    This is a book written primarily for graduate students and early researchers in the fields of Analysis and Partial Differential Equations (PDEs). Coverage of the material is essentially self-contained, extensive and novel with great attention to details and rigour.

  9. Molecular marker analysis to differentiate a clonal selection of ...

    African Journals Online (AJOL)

    Lalit Kumar

    2013-04-03

    Apr 3, 2013 ... Microsatellite and amplified fragment length polymorphism (AFLP) markers were used to differentiate. Manjari Naveen, a clonal selection of Centennial Seedless variety of grape. Twenty one (21) microsatellite primers could not detect variation between parent variety and its clone. AFLP analysis.

  10. Cis-Natural Antisense Transcripts Are Mainly Co-expressed with Their Sense Transcripts and Primarily Related to Energy Metabolic Pathways during Muscle Development.

    Science.gov (United States)

    Zhao, Yunxia; Hou, Ye; Zhao, Changzhi; Liu, Fei; Luan, Yu; Jing, Lu; Li, Xinyun; Zhu, Mengjin; Zhao, Shuhong

    2016-01-01

    Cis-natural antisense transcripts (cis-NATs) are a new class of RNAs identified in various species. However, the biological functions of cis-NATs are largely unknown. In this study, we investigated the transcriptional characteristics and functions of cis-NATs in the muscle tissue of lean Landrace and indigenous fatty Lantang pigs. In total, 3,306 cis-NATs of 2,469 annotated genes were identified in the muscle tissue of pigs. More than 1,300 cis-NATs correlated with their sense genes at the transcriptional level, and approximately 80% of them were co-expressed in the two breeds. Furthermore, over 1,200 differentially expressed cis-NATs were identified during muscle development. Function annotation showed that the cis-NATs participated in muscle development mainly by co-expressing with genes involved in energy metabolic pathways, including citrate cycle (TCA cycle), glycolysis or gluconeogenesis, mitochondrial activation and so on. Moreover, these cis-NATs and their sense genes abruptly increased at the transition from the late fetal stages to the early postnatal stages and then decreased along with muscle development. In conclusion, the cis-NATs in the muscle tissue of pigs were identified and determined to be mainly co-expressed with their sense genes. The co-expressed cis-NATs and their sense gene were primarily related to energy metabolic pathways during muscle development in pigs. Our results offered novel evidence on the roles of cis-NATs during the muscle development of pigs.

  11. Tensor analysis and elementary differential geometry for physicists and engineers

    CERN Document Server

    Nguyen-Schäfer, Hung

    2014-01-01

    Tensors and methods of differential geometry are very useful mathematical tools in many fields of modern physics and computational engineering including relativity physics, electrodynamics, computational fluid dynamics (CFD), continuum mechanics, aero and vibroacoustics, and cybernetics. This book comprehensively presents topics, such as bra-ket notation, tensor analysis, and elementary differential geometry of a moving surface. Moreover, authors intentionally abstain from giving mathematically rigorous definitions and derivations that are however dealt with as precisely as possible. The reader is provided with hands-on calculations and worked-out examples at which he will learn how to handle the bra-ket notation, tensors and differential geometry and to use them in the physical and engineering world. The target audience primarily comprises graduate students in physics and engineering, research scientists, and practicing engineers.

  12. Uncovering robust patterns of microRNA co-expression across cancers using Bayesian Relevance Networks.

    Directory of Open Access Journals (Sweden)

    Parameswaran Ramachandran

    Full Text Available Co-expression networks have long been used as a tool for investigating the molecular circuitry governing biological systems. However, most algorithms for constructing co-expression networks were developed in the microarray era, before high-throughput sequencing-with its unique statistical properties-became the norm for expression measurement. Here we develop Bayesian Relevance Networks, an algorithm that uses Bayesian reasoning about expression levels to account for the differing levels of uncertainty in expression measurements between highly- and lowly-expressed entities, and between samples with different sequencing depths. It combines data from groups of samples (e.g., replicates to estimate group expression levels and confidence ranges. It then computes uncertainty-moderated estimates of cross-group correlations between entities, and uses permutation testing to assess their statistical significance. Using large scale miRNA data from The Cancer Genome Atlas, we show that our Bayesian update of the classical Relevance Networks algorithm provides improved reproducibility in co-expression estimates and lower false discovery rates in the resulting co-expression networks. Software is available at www.perkinslab.ca.

  13. Gene co-expression networks and profiles reveal potential biomarkers of boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Skinkyté-Juskiené, R.; Do, Duy Ngoc

    synthesis. In testis, >80 DE genes were functionally classified by the PANTHER tool to “Gonadotropin releasing hormone receptor” and “Wnt signaling” pathways which play a role in reproductive maturation and proliferation of spermatogonia, respectively. WGCNA was used to build co-expression modules...

  14. Different substrate regimes determine transcriptional profiles and gene co-expression in Methanosarcina barkeri (DSM 800)

    Czech Academy of Sciences Publication Activity Database

    Lin, Qiang; Fang, X.; Ho, A.; Li, J.; Yan, X.; Tu, B.; Li, Ch.; Li, J.; Yao, M.; Li, X.

    2017-01-01

    Roč. 101, č. 19 (2017), s. 7303-7316 ISSN 0175-7598 Institutional support: RVO:60077344 Keywords : Methanosarcina barkeri * substrate regimes * diversity * co-expression * ecological strategies Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 3.420, year: 2016

  15. Co-expression of the C-terminal domain of Yersinia enterocolitica ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 40; Issue 1. Co-expression of the C-terminal domain of Yersinia enterocolitica invasin enhances the efficacy of classical swine-fever-vectored vaccine based on human adenovirus. Helin Li Pengbo Ning Zhi Lin Wulong Liang Kai Kang Lei He Yanming Zhang. Articles Volume ...

  16. Analysis of pharmacogenomic variants associated with population differentiation.

    Directory of Open Access Journals (Sweden)

    Bora Yeon

    Full Text Available In the present study, we systematically investigated population differentiation of drug-related (DR genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA F-test, Fst, and Nearest Shrunken Centroid Method (NSCM. Fst showed high sensitivity with stable specificity among varying sample sizes; thus, we selected Fst for determining population differentiation. Second, we divided DR genes from PharmGKB into two groups based on the degree of population differentiation as assessed by Fst: genes with a high level of differentiation (HD gene group and genes with a low level of differentiation (LD gene group. Last, we conducted a gene ontology (GO analysis and pathway analysis. Using all genes in the human genome as the background, the GO analysis and pathway analysis of the HD genes identified terms related to cell communication. "Cell communication" and "cell-cell signaling" had the lowest Benjamini-Hochberg's q-values (0.0002 and 0.0006, respectively, and "drug binding" was highly enriched (16.51 despite its relatively high q-value (0.0142. Among the 17 genes related to cell communication identified in the HD gene group, five genes (STX4, PPARD, DCK, GRIK4, and DRD3 contained single nucleotide polymorphisms with Fst values greater than 0.5. Specifically, the Fst values for rs10871454, rs6922548, rs3775289, rs1954787, and rs167771 were 0.682, 0.620, 0.573, 0.531, and 0.510, respectively. In the analysis using DR genes as the background, the HD gene group contained six significant terms. Five were related to reproduction, and one was "Wnt signaling pathway," which has been implicated in cancer. Our analysis suggests that the HD gene group from PharmGKB is

  17. Analysis of pharmacogenomic variants associated with population differentiation.

    Science.gov (United States)

    Yeon, Bora; Ahn, Eunyong; Kim, Kyung-Im; Kim, In-Wha; Oh, Jung Mi; Park, Taesung

    2015-01-01

    In the present study, we systematically investigated population differentiation of drug-related (DR) genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB) database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA) F-test, Fst, and Nearest Shrunken Centroid Method (NSCM). Fst showed high sensitivity with stable specificity among varying sample sizes; thus, we selected Fst for determining population differentiation. Second, we divided DR genes from PharmGKB into two groups based on the degree of population differentiation as assessed by Fst: genes with a high level of differentiation (HD gene group) and genes with a low level of differentiation (LD gene group). Last, we conducted a gene ontology (GO) analysis and pathway analysis. Using all genes in the human genome as the background, the GO analysis and pathway analysis of the HD genes identified terms related to cell communication. "Cell communication" and "cell-cell signaling" had the lowest Benjamini-Hochberg's q-values (0.0002 and 0.0006, respectively), and "drug binding" was highly enriched (16.51) despite its relatively high q-value (0.0142). Among the 17 genes related to cell communication identified in the HD gene group, five genes (STX4, PPARD, DCK, GRIK4, and DRD3) contained single nucleotide polymorphisms with Fst values greater than 0.5. Specifically, the Fst values for rs10871454, rs6922548, rs3775289, rs1954787, and rs167771 were 0.682, 0.620, 0.573, 0.531, and 0.510, respectively. In the analysis using DR genes as the background, the HD gene group contained six significant terms. Five were related to reproduction, and one was "Wnt signaling pathway," which has been implicated in cancer. Our analysis suggests that the HD gene group from PharmGKB is associated with

  18. Functional analysis in the study of differential and integral equations

    International Nuclear Information System (INIS)

    Sell, G.R.

    1976-01-01

    This paper illustrates the use of functional analysis in the study of differential equations. Our particular starting point, the theory of flows or dynamical systems, originated with the work of H. Poincare, who is the founder of the qualitative theory of ordinary differential equations. In the qualitative theory one tries to describe the behaviour of a solution, or a collection of solutions, without ''solving'' the differential equation. As a starting point one assumes the existence, and sometimes the uniqueness, of solutions and then one tries to describe the asymptotic behaviour, as time t→+infinity, of these solutions. We compare the notion of a flow with that of a C 0 -group of bounded linear operators on a Banach space. We shall show how the concept C 0 -group, or more generally a C 0 -semigroup, can be used to study the behaviour of solutions of certain differential and integral equations. Our main objective is to show how the concept of a C 0 -group and especially the notion of weak-compactness can be used to prove the existence of an invariant measure for a flow on a compact Hausdorff space. Applications to the theory of ordinary differential equations are included. (author)

  19. Comparison of co-expression measures: mutual information, correlation, and model based indices.

    Science.gov (United States)

    Song, Lin; Langfelder, Peter; Horvath, Steve

    2012-12-09

    Co-expression measures are often used to define networks among genes. Mutual information (MI) is often used as a generalized correlation measure. It is not clear how much MI adds beyond standard (robust) correlation measures or regression model based association measures. Further, it is important to assess what transformations of these and other co-expression measures lead to biologically meaningful modules (clusters of genes). We provide a comprehensive comparison between mutual information and several correlation measures in 8 empirical data sets and in simulations. We also study different approaches for transforming an adjacency matrix, e.g. using the topological overlap measure. Overall, we confirm close relationships between MI and correlation in all data sets which reflects the fact that most gene pairs satisfy linear or monotonic relationships. We discuss rare situations when the two measures disagree. We also compare correlation and MI based approaches when it comes to defining co-expression network modules. We show that a robust measure of correlation (the biweight midcorrelation transformed via the topological overlap transformation) leads to modules that are superior to MI based modules and maximal information coefficient (MIC) based modules in terms of gene ontology enrichment. We present a function that relates correlation to mutual information which can be used to approximate the mutual information from the corresponding correlation coefficient. We propose the use of polynomial or spline regression models as an alternative to MI for capturing non-linear relationships between quantitative variables. The biweight midcorrelation outperforms MI in terms of elucidating gene pairwise relationships. Coupled with the topological overlap matrix transformation, it often leads to more significantly enriched co-expression modules. Spline and polynomial networks form attractive alternatives to MI in case of non-linear relationships. Our results indicate that MI

  20. Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

    Directory of Open Access Journals (Sweden)

    Schininà Maria

    2010-09-01

    Full Text Available Abstract Background Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE combined with mass spectrometry. Results In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible. Conclusions The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the

  1. From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

    Science.gov (United States)

    Vella, Danila; Zoppis, Italo; Mauri, Giancarlo; Mauri, Pierluigi; Di Silvestre, Dario

    2017-12-01

    The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.

  2. Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

    Directory of Open Access Journals (Sweden)

    Arundhoti Das

    TFs, and their cytokine commitment varied depending on genetic background or priming conditions, without altering pattern of TF co-expression. Thus, the model of mutually antagonistic differentiation programs driven by mutually exclusively expressed T-bet or GATA-3 does not completely explain natural CD4 T cell priming outcomes.

  3. Co-expression of TIMP-1 and its cell surface binding partner CD63 in glioblastomas

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Sørensen, Mia D.; Matos, Ana L.S.A.

    2018-01-01

    scoring. CD63 expression in tumor-associated microglia/macrophages was examined by double-immunofluorescence with ionized calcium-binding adapter molecule 1 (Iba1). The association between CD63 and TIMP-1 was investigated using previously obtained TIMP-1 data from our astrocytoma cohort. Cellular co-expression...... of CD63 was widely distributed in astrocytomas with a significantly increased level in glioblastomas. CD63 levels did not significantly correlate with patient survival at a protein level, and CD63 did not augment the prognostic significance of TIMP-1. Up to 38% of the CD63+ cells expressed Iba1; however......, Iba1 did not appear to impact the prognostic value of CD63. A significant correlation was found between TIMP-1 and CD63, and the TIMP-1 and CD63 proteins were co-expressed at the cellular level and located in close molecular proximity, suggesting that TIMP-1 and CD63 could be co...

  4. PC analysis of stochastic differential equations driven by Wiener noise

    KAUST Repository

    Le Maitre, Olivier

    2015-03-01

    A polynomial chaos (PC) analysis with stochastic expansion coefficients is proposed for stochastic differential equations driven by additive or multiplicative Wiener noise. It is shown that for this setting, a Galerkin formalism naturally leads to the definition of a hierarchy of stochastic differential equations governing the evolution of the PC modes. Under the mild assumption that the Wiener and uncertain parameters can be treated as independent random variables, it is also shown that the Galerkin formalism naturally separates parametric uncertainty and stochastic forcing dependences. This enables us to perform an orthogonal decomposition of the process variance, and consequently identify contributions arising from the uncertainty in parameters, the stochastic forcing, and a coupled term. Insight gained from this decomposition is illustrated in light of implementation to simplified linear and non-linear problems; the case of a stochastic bifurcation is also considered.

  5. Teacher knowledge of error analysis in differential calculus

    Directory of Open Access Journals (Sweden)

    Eunice K. Moru

    2014-12-01

    Full Text Available The study investigated teacher knowledge of error analysis in differential calculus. Two teachers were the sample of the study: one a subject specialist and the other a mathematics education specialist. Questionnaires and interviews were used for data collection. The findings of the study reflect that the teachers’ knowledge of error analysis was characterised by the following assertions, which are backed up with some evidence: (1 teachers identified the errors correctly, (2 the generalised error identification resulted in opaque analysis, (3 some of the identified errors were not interpreted from multiple perspectives, (4 teachers’ evaluation of errors was either local or global and (5 in remedying errors accuracy and efficiency were emphasised more than conceptual understanding. The implications of the findings of the study for teaching include engaging in error analysis continuously as this is one way of improving knowledge for teaching.

  6. Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

    Directory of Open Access Journals (Sweden)

    Recep Colak

    2010-10-01

    Full Text Available Computational prediction of functionally related groups of genes (functional modules from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented.We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB, by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples.We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely

  7. Characterization of chemically induced liver injuries using gene co-expression modules.

    Directory of Open Access Journals (Sweden)

    Gregory J Tawa

    Full Text Available Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20% genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

  8. Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

    Science.gov (United States)

    Colak, Recep; Moser, Flavia; Chu, Jeffrey Shih-Chieh; Schönhuth, Alexander; Chen, Nansheng; Ester, Martin

    2010-10-25

    Computational prediction of functionally related groups of genes (functional modules) from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense) regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented. We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB), by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples. We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely available large

  9. FastGCN: a GPU accelerated tool for fast gene co-expression networks.

    Directory of Open Access Journals (Sweden)

    Meimei Liang

    Full Text Available Gene co-expression networks comprise one type of valuable biological networks. Many methods and tools have been published to construct gene co-expression networks; however, most of these tools and methods are inconvenient and time consuming for large datasets. We have developed a user-friendly, accelerated and optimized tool for constructing gene co-expression networks that can fully harness the parallel nature of GPU (Graphic Processing Unit architectures. Genetic entropies were exploited to filter out genes with no or small expression changes in the raw data preprocessing step. Pearson correlation coefficients were then calculated. After that, we normalized these coefficients and employed the False Discovery Rate to control the multiple tests. At last, modules identification was conducted to construct the co-expression networks. All of these calculations were implemented on a GPU. We also compressed the coefficient matrix to save space. We compared the performance of the GPU implementation with those of multi-core CPU implementations with 16 CPU threads, single-thread C/C++ implementation and single-thread R implementation. Our results show that GPU implementation largely outperforms single-thread C/C++ implementation and single-thread R implementation, and GPU implementation outperforms multi-core CPU implementation when the number of genes increases. With the test dataset containing 16,000 genes and 590 individuals, we can achieve greater than 63 times the speed using a GPU implementation compared with a single-thread R implementation when 50 percent of genes were filtered out and about 80 times the speed when no genes were filtered out.

  10. Differential network analysis with multiply imputed lipidomic data.

    Directory of Open Access Journals (Sweden)

    Maiju Kujala

    Full Text Available The importance of lipids for cell function and health has been widely recognized, e.g., a disorder in the lipid composition of cells has been related to atherosclerosis caused cardiovascular disease (CVD. Lipidomics analyses are characterized by large yet not a huge number of mutually correlated variables measured and their associations to outcomes are potentially of a complex nature. Differential network analysis provides a formal statistical method capable of inferential analysis to examine differences in network structures of the lipids under two biological conditions. It also guides us to identify potential relationships requiring further biological investigation. We provide a recipe to conduct permutation test on association scores resulted from partial least square regression with multiple imputed lipidomic data from the LUdwigshafen RIsk and Cardiovascular Health (LURIC study, particularly paying attention to the left-censored missing values typical for a wide range of data sets in life sciences. Left-censored missing values are low-level concentrations that are known to exist somewhere between zero and a lower limit of quantification. To make full use of the LURIC data with the missing values, we utilize state of the art multiple imputation techniques and propose solutions to the challenges that incomplete data sets bring to differential network analysis. The customized network analysis helps us to understand the complexities of the underlying biological processes by identifying lipids and lipid classes that interact with each other, and by recognizing the most important differentially expressed lipids between two subgroups of coronary artery disease (CAD patients, the patients that had a fatal CVD event and the ones who remained stable during two year follow-up.

  11. Multivariable Discriminant Analysis for the Differential Diagnosis of Microcytic Anemia

    Directory of Open Access Journals (Sweden)

    Eloísa Urrechaga

    2013-01-01

    Full Text Available Introduction. Iron deficiency anemia and thalassemia are the most common causes of microcytic anemia. Powerful statistical computer programming enables sensitive discriminant analyses to aid in the diagnosis. We aimed at investigating the performance of the multiple discriminant analysis (MDA to the differential diagnosis of microcytic anemia. Methods. The training group was composed of 200 β-thalassemia carriers, 65 α-thalassemia carriers, 170 iron deficiency anemia (IDA, and 45 mixed cases of thalassemia and acute phase response or iron deficiency. A set of potential predictor parameters that could detect differences among groups were selected: Red Blood Cells (RBC, hemoglobin (Hb, mean cell volume (MCV, mean cell hemoglobin (MCH, and RBC distribution width (RDW. The functions obtained with MDA analysis were applied to a set of 628 consecutive patients with microcytic anemia. Results. For classifying patients into two groups (genetic anemia and acquired anemia, only one function was needed; 87.9% β-thalassemia carriers, and 83.3% α-thalassemia carriers, and 72.1% in the mixed group were correctly classified. Conclusion. Linear discriminant functions based on hemogram data can aid in differentiating between IDA and thalassemia, so samples can be efficiently selected for further analysis to confirm the presence of genetic anemia.

  12. Clonal analysis of stem cells in differentiation and disease.

    Science.gov (United States)

    Colom, Bartomeu; Jones, Philip H

    2016-12-01

    Tracking the fate of individual cells and their progeny by clonal analysis has redefined the concept of stem cells and their role in health and disease. The maintenance of cell turnover in adult tissues is achieved by the collective action of populations of stem cells with an equal likelihood of self-renewal or differentiation. Following injury stem cells exhibit striking plasticity, switching from homeostatic behavior in order to repair damaged tissues. The effects of disease states on stem cells are also being uncovered, with new insights into how somatic mutations trigger clonal expansion in early neoplasia. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

    Science.gov (United States)

    2013-01-01

    Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize

  14. Spaceborne Differential SAR Interferometry: Data Analysis Tools for Deformation Measurement

    Directory of Open Access Journals (Sweden)

    Michele Crosetto

    2011-02-01

    Full Text Available This paper is focused on spaceborne Differential Interferometric SAR (DInSAR for land deformation measurement and monitoring. In the last two decades several DInSAR data analysis procedures have been proposed. The objective of this paper is to describe the DInSAR data processing and analysis tools developed at the Institute of Geomatics in almost ten years of research activities. Four main DInSAR analysis procedures are described, which range from the standard DInSAR analysis based on a single interferogram to more advanced Persistent Scatterer Interferometry (PSI approaches. These different procedures guarantee a sufficient flexibility in DInSAR data processing. In order to provide a technical insight into these analysis procedures, a whole section discusses their main data processing and analysis steps, especially those needed in PSI analyses. A specific section is devoted to the core of our PSI analysis tools: the so-called 2+1D phase unwrapping procedure, which couples a 2D phase unwrapping, performed interferogram-wise, with a kind of 1D phase unwrapping along time, performed pixel-wise. In the last part of the paper, some examples of DInSAR results are discussed, which were derived by standard DInSAR or PSI analyses. Most of these results were derived from X-band SAR data coming from the TerraSAR-X and CosmoSkyMed sensors.

  15. Inference for High-dimensional Differential Correlation Matrices.

    Science.gov (United States)

    Cai, T Tony; Zhang, Anru

    2016-01-01

    Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed.

  16. DDASAC, Double-Precision Differential or Algebraic Sensitivity Analysis

    International Nuclear Information System (INIS)

    Caracotsios, M.; Stewart, W.E.; Petzold, L.

    1997-01-01

    1 - Description of program or function: DDASAC solves nonlinear initial-value problems involving stiff implicit systems of ordinary differential and algebraic equations. Purely algebraic nonlinear systems can also be solved, given an initial guess within the region of attraction of a solution. Options include automatic reconciliation of inconsistent initial states and derivatives, automatic initial step selection, direct concurrent parametric sensitivity analysis, and stopping at a prescribed value of any user-defined functional of the current solution vector. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the sensitivities on request. 2 - Method of solution: Reconciliation of initial conditions is done with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithm of Shampine (1987), extended here to differential-algebraic equation systems. The solution is continued with the DASSL predictor- corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase detected and with row scaling of the Jacobian added. The backward-difference formulas for the predictor and corrector are expressed in divide-difference form, and the fixed-leading-coefficient form of the corrector (Jackson and Sacks-Davis 1980, Brenan et al. 1989) is used. Weights for error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations as given by Catacotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigns the work array lengths and the output unit. The machine number range and precision are determined at run time by a

  17. Differentiation of closely related fungi by electronic nose analysis

    DEFF Research Database (Denmark)

    Karlshøj, Kristian; Nielsen, Per Væggemose; Larsen, Thomas Ostenfeld

    2007-01-01

    the electronic nose potentially responded to, volatile metabolites were collected, by diffusive sampling overnight onto tubes containing Tenax TA, between the 7th and 8th day of Incubation.Volatiles were analyzed by gas chromatography coupled to mass spectrometry and the results indicated that mail alcohols...... as well as the noacheese ociated P. expansum have been investigated by electronic nose, GC-MS, and LGMS analysis. The isolates were inoculated on yeast extract sucroseagar in 20-mL headspace flasks and electronicnose analysis was performed daily for a-74period. To assess which volatile metabolites...... by high pressure liquid chromatography, coupled-to a diode array detector and a time of flight mass spectrometer. Several mycotoxins were detected in samples from the specles P.nordicum, P.roqueforti, P.paneum, P.carneum, and P.expansum. Differentiation of closely related mycotoxin producing fungi...

  18. A statistical framework for differential network analysis from microarray data

    Directory of Open Access Journals (Sweden)

    Datta Somnath

    2010-02-01

    Full Text Available Abstract Background It has been long well known that genes do not act alone; rather groups of genes act in consort during a biological process. Consequently, the expression levels of genes are dependent on each other. Experimental techniques to detect such interacting pairs of genes have been in place for quite some time. With the advent of microarray technology, newer computational techniques to detect such interaction or association between gene expressions are being proposed which lead to an association network. While most microarray analyses look for genes that are differentially expressed, it is of potentially greater significance to identify how entire association network structures change between two or more biological settings, say normal versus diseased cell types. Results We provide a recipe for conducting a differential analysis of networks constructed from microarray data under two experimental settings. At the core of our approach lies a connectivity score that represents the strength of genetic association or interaction between two genes. We use this score to propose formal statistical tests for each of following queries: (i whether the overall modular structures of the two networks are different, (ii whether the connectivity of a particular set of "interesting genes" has changed between the two networks, and (iii whether the connectivity of a given single gene has changed between the two networks. A number of examples of this score is provided. We carried out our method on two types of simulated data: Gaussian networks and networks based on differential equations. We show that, for appropriate choices of the connectivity scores and tuning parameters, our method works well on simulated data. We also analyze a real data set involving normal versus heavy mice and identify an interesting set of genes that may play key roles in obesity. Conclusions Examining changes in network structure can provide valuable information about the

  19. Penalized differential pathway analysis of integrative oncogenomics studies.

    Science.gov (United States)

    van Wieringen, Wessel N; van de Wiel, Mark A

    2014-04-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

  20. Differential DNA Methylation Analysis without a Reference Genome

    Directory of Open Access Journals (Sweden)

    Johanna Klughammer

    2015-12-01

    Full Text Available Genome-wide DNA methylation mapping uncovers epigenetic changes associated with animal development, environmental adaptation, and species evolution. To address the lack of high-throughput methods for DNA methylation analysis in non-model organisms, we developed an integrated approach for studying DNA methylation differences independent of a reference genome. Experimentally, our method relies on an optimized 96-well protocol for reduced representation bisulfite sequencing (RRBS, which we have validated in nine species (human, mouse, rat, cow, dog, chicken, carp, sea bass, and zebrafish. Bioinformatically, we developed the RefFreeDMA software to deduce ad hoc genomes directly from RRBS reads and to pinpoint differentially methylated regions between samples or groups of individuals (http://RefFreeDMA.computational-epigenetics.org. The identified regions are interpreted using motif enrichment analysis and/or cross-mapping to annotated genomes. We validated our method by reference-free analysis of cell-type-specific DNA methylation in the blood of human, cow, and carp. In summary, we present a cost-effective method for epigenome analysis in ecology and evolution, which enables epigenome-wide association studies in natural populations and species without a reference genome.

  1. Analysis of backward differentiation formula for nonlinear differential-algebraic equations with 2 delays.

    Science.gov (United States)

    Sun, Leping

    2016-01-01

    This paper is concerned with the backward differential formula or BDF methods for a class of nonlinear 2-delay differential algebraic equations. We obtain two sufficient conditions under which the methods are stable and asymptotically stable. At last, examples show that our methods are true.

  2. Viscoelastic Plate Analysis Based on Gâteaux Differential

    Directory of Open Access Journals (Sweden)

    Kadıoğlu Fethi

    2016-01-01

    Full Text Available In this study, it is aimed to analyze the quasi-static response of viscoelastic Kirchhoff plates with mixed finite element formulation based on the Gâteaux differential. Although the static response of elastic plate, beam and shell structures is a widely studied topic, there are few studies that exist in the literature pertaining to the analysis of the viscoelastic structural elements especially with complex geometries, loading conditions and constitutive relations. The developed mixed finite element model in transformed Laplace-Carson space has four unknowns as displacement, bending and twisting moments in addition to the dynamic and geometric boundary condition terms. Four-parameter solid model is employed for modelling the viscoelastic behaviour. For transformation of the solutions obtained in the Laplace-Carson domain to the time domain, different numerical inverse transform techniques are employed. The developed solution technique is applied to several quasi-static example problems for the verification of the suggested numerical procedure.

  3. Once for All: A Novel Robust System for Co-expression of Multiple Chimeric Fluorescent Fusion Proteins in Plants

    Directory of Open Access Journals (Sweden)

    Guitao Zhong

    2017-06-01

    Full Text Available Chimeric fluorescent fusion proteins have been employed as a powerful tool to reveal the subcellular localizations and dynamics of proteins in living cells. Co-expression of a fluorescent fusion protein with well-known organelle markers in the same cell is especially useful in revealing its spatial and temporal functions of the protein in question. However, the conventional methods for co-expressing multiple fluorescent tagged proteins in plants have the drawbacks of low expression efficiency, variations in the expression level and time-consuming genetic crossing. Here, we have developed a novel robust system that allows for high-efficient co-expression of multiple chimeric fluorescent fusion proteins in plants in a time-saving fashion. This system takes advantage of employing a single expression vector which consists of multiple semi-independent expressing cassettes for the protein co-expression thereby overcoming the limitations of using multiple independent expressing plasmids. In addition, it is a highly manipulable DNA assembly system, in which modification and recombination of DNA molecules are easily achieved through an optimized one-step assembly reaction. By employing this effective system, we demonstrated that co-expression of two chimeric fluorescent fusion reporter proteins of vacuolar sorting receptor and secretory carrier membrane protein gave rise to their perspective subcellular localizations in plants via both transient expression and stable transformation. Thus, we believed that this technical advance represents a promising approach for multi-color-protein co-expression in plant cells.

  4. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  5. Co-expression of G2-EPSPS and glyphosate acetyltransferase GAT genes conferring high tolerance to glyphosate in soybean

    Directory of Open Access Journals (Sweden)

    Bingfu eGuo

    2015-10-01

    Full Text Available Glyphosate is a widely used non-selective herbicide with broad spectrum of weed control around the world. At present, most of the commercial glyphosate tolerant soybeans utilize glyphosate tolerant gene CP4-EPSPS or glyphosate acetyltransferase gene GAT separately. In this study, both glyphosate tolerant gene G2-EPSPS and glyphosate degraded gene GAT were co-transferred into soybean and transgenic plants showed high tolerance to glyphosate. Molecular analysis including PCR, Sothern blot, qRT-PCR and Western blot revealed that target genes have been integrated into genome and expressed effectively at both mRNA and protein levels. Furthermore, the glyphosate tolerance analysis showed that no typical symptom was observed when compared with a glyphosate tolerant line HJ06-698 derived from GR1 transgenic soybean even at four-fold labeled rate of Roundup. Chlorophyll and shikimic acid content analysis of transgenic plant also revealed that these two indexes were not significantly altered after glyphosate application. These results indicated that co-expression of G2-EPSPS and GAT conferred high tolerance to the herbicide glyphosate in soybean. Therefore, combination of tolerant and degraded genes provides a new strategy for developing glyphosate tolerant transgenic crops.

  6. MPIGeneNet: Parallel Calculation of Gene Co-Expression Networks on Multicore Clusters.

    Science.gov (United States)

    Gonzalez-Dominguez, Jorge; Martin, Maria J

    2017-10-10

    In this work we present MPIGeneNet, a parallel tool that applies Pearson's correlation and Random Matrix Theory to construct gene co-expression networks. It is based on the state-of-the-art sequential tool RMTGeneNet, which provides networks with high robustness and sensitivity at the expenses of relatively long runtimes for large scale input datasets. MPIGeneNet returns the same results as RMTGeneNet but improves the memory management, reduces the I/O cost, and accelerates the two most computationally demanding steps of co-expression network construction by exploiting the compute capabilities of common multicore CPU clusters. Our performance evaluation on two different systems using three typical input datasets shows that MPIGeneNet is significantly faster than RMTGeneNet. As an example, our tool is up to 175.41 times faster on a cluster with eight nodes, each one containing two 12-core Intel Haswell processors. Source code of MPIGeneNet, as well as a reference manual, are available at https://sourceforge.net/projects/mpigenenet/.

  7. Exploring the Diagnostic Potential of Immune Biomarker Co-expression in Gulf War Illness.

    Science.gov (United States)

    Broderick, Gordon; Fletcher, Mary Ann; Gallagher, Michael; Barnes, Zachary; Vernon, Suzanne D; Klimas, Nancy G

    2018-01-01

    Complex disorders like Gulf War illness (GWI) often defy diagnosis on the basis of a single biomarker and may only be distinguishable by considering the co-expression of multiple markers measured in response to a challenge. We demonstrate the practical application of such an approach using an example where blood was collected from 26 GWI, 13 healthy control subjects, and 9 unhealthy controls with chronic fatigue at three points during a graded exercise challenge. A 3-way multivariate projection model based on 12 markers of endocrine and immune function was constructed using a training set of n = 10 GWI and n = 11 healthy controls. These groups were separated almost completely on the basis of two co-expression patterns. In a separate test set these same features allowed for discrimination of new GWI subjects (n = 16) from unhealthy (n = 9) and healthy control subjects with a sensitivity of 70% and a specificity of 90%.

  8. Autocrine CSF-1 and CSF-1 Receptor Co-expression Promotes Renal Cell Carcinoma Growth

    Science.gov (United States)

    Menke, Julia; Kriegsmann, Jörg; Schimanski, Carl Christoph; Schwartz, Melvin M.; Schwarting, Andreas; Kelley, Vicki R.

    2011-01-01

    Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Co-expression of the monocytic growth factor CSF-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and anti-apoptosis during regeneration of renal tubules. Here we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were co-expressed in RCC and TEC proximally adjacent to RCC. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and EGF signaling in RCC. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R and EGF expression in RCC. Further, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCC. PMID:22052465

  9. A contribution to the study of plant development evolution based on gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Francisco J. Romero-Campero

    2013-08-01

    Full Text Available Phototrophic eukaryotes are among the most successful organisms on Earth due to their unparalleled efficiency at capturing light energy and fixing carbon dioxide to produce organic molecules. A conserved and efficient network of light-dependent regulatory modules could be at the bases of this success. This regulatory system conferred early advantages to phototrophic eukaryotes that allowed for specialization, complex developmental processes and modern plant characteristics. We have studied light-dependent gene regulatory modules from algae to plants employing integrative-omics approaches based on gene co-expression networks. Our study reveals some remarkably conserved ways in which eukaryotic phototrophs deal with day length and light signaling. Here we describe how a family of Arabidopsis transcription factors involved in photoperiod response has evolved from a single algal gene according to the innovation, amplification and divergence theory of gene evolution by duplication. These modifications of the gene co-expression networks from the ancient unicellular green algae Chlamydomonas reinhardtii to the modern brassica Arabidopsis thaliana may hint on the evolution and specialization of plants and other organisms.

  10. A Network Approach of Gene Co-expression in the Zea mays/Aspergillus flavus Pathosystem to Map Host/Pathogen Interaction Pathways

    OpenAIRE

    Musungu, Bryan M.; Bhatnagar, Deepak; Brown, Robert L.; Payne, Gary A.; OBrian, Greg; Fakhoury, Ahmad M.; Geisler, Matt

    2016-01-01

    A gene co-expression network (GEN) was generated using a dual RNA-seq study with the fungal pathogen Aspergillus flavus and its plant host Zea mays during the initial 3 days of infection. The analysis deciphered novel pathways and mapped genes of interest in both organisms during the infection. This network revealed a high degree of connectivity in many of the previously recognized pathways in Z. mays such as jasmonic acid, ethylene, and reactive oxygen species (ROS). For the pathogen A. flav...

  11. PDASAC, Partial Differential Sensitivity Analysis of Stiff System

    International Nuclear Information System (INIS)

    Caracotsios, M.; Stewart, W.E.

    2001-01-01

    1 - Description of program or function: PDASAC solves stiff, nonlinear initial-boundary-value problems in a timelike dimension t and a space dimension x. Plane, circular cylindrical or spherical boundaries can be handled. Mixed-order systems of partial differential and algebraic equations can be analyzed with members of order or 0 or 1 in t, 0, 1 or 2 in x. Parametric sensitivities of the calculated states are computed simultaneously on request, via the Jacobian of the state equations. Initial and boundary conditions are efficiently reconciled. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the parametric sensitivities if desired. 2 - Method of solution: The method of lines is used, with a user- selected x-grid and a minimum-bandwidth finite-difference approximations of the x-derivatives. Starting conditions are reconciled with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithms of Shampine (1987), extended here to differential- algebraic equation systems. The solution is continued with the DASSL predictor-corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase deleted and with row scaling of the Jacobian added. The predictor and corrector are expressed in divided-difference form, with the fixed-leading-coefficient form of corrector (Jackson and Sacks-Davis 1989; Brenan et al. 1989). Weights for the error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations of Caracotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic equation systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigned the work array lengths and the output

  12. S187. SEARCHING FOR BRAIN CO-EXPRESSION MODULES THAT CONTRIBUTE DISPROPORTIONATELY TO THE COMMON POLYGENIC RISK FOR SCHIZOPHRENIA

    Science.gov (United States)

    Costas, Javier; Paramo, Mario; Arrojo, Manuel

    2018-01-01

    Abstract Background Genomic research has revealed that schizophrenia is a highly polygenic disease. Recent estimates indicate that at least 71% of genomic segments of 1 Mb include one or more risk loci for schizophrenia (Loh et al., Nature Genet 2015). This extremely high polygenicity represents a challenge to decipher the biological basis of schizophrenia, as it is expected that any set of SNPs with enough size will be associated with the disorder. Among the different gene sets available for study (such as those from Gene Ontology, KEGG pathway, Reactome pathways or protein protein interaction datasets), those based on brain co-expression networks represent putative functional relationships in the relevant tissue. The aim of this work was to identify brain co-expression networks that contribute disproportionately to the common polygenic risk for schizophrenia to get more insight on schizophrenia etiopathology. Methods We analyzed a case -control dataset consisting of 582 schizophrenia patients from Galicia, NW Spain, and 591 ancestrally matched controls, genotyped with the Illumina PsychArray. Using as discovery sample the summary results from the largest GWAS of schizophrenia to date (Psychiatric Genomics Consortium, SCZ2), we generated polygenic risk scores (PRS) in our sample based on SNPs located at genes belonging to brain co-expression modules determined by the CommonMind Consortium (Fromer et al., Nature Neurosci 2016). PRS were generated using the clumping procedure of PLINK, considering several different thresholds to select SNPs from the discovery sample. In order to test if any specific module increased risk to schizophrenia more than expected by their size, we generated up to 10,000 random permutations of the same number of SNPs, matched by frequency, distance to nearest gene, number of SNPs in LD and gene density, using SNPsnap. Results As expected, most modules with enough number of independent SNPs belonging to them showed a significant increase in

  13. Hydroxylation of recombinant human collagen type I alpha 1 in transgenic maize co-expressed with a recombinant human prolyl 4-hydroxylase

    Directory of Open Access Journals (Sweden)

    Pappu Kameshwari M

    2011-06-01

    Full Text Available Abstract Background Collagens require the hydroxylation of proline (Pro residues in their triple-helical domain repeating sequence Xaa-Pro-Gly to function properly as a main structural component of the extracellular matrix in animals at physiologically relevant conditions. The regioselective proline hydroxylation is catalyzed by a specific prolyl 4-hydroxylase (P4H as a posttranslational processing step. Results A recombinant human collagen type I α-1 (rCIα1 with high percentage of hydroxylated prolines (Hyp was produced in transgenic maize seeds when co-expressed with both the α- and β- subunits of a recombinant human P4H (rP4H. Germ-specific expression of rCIα1 using maize globulin-1 gene promoter resulted in an average yield of 12 mg/kg seed for the full-length rCIα1 in seeds without co-expression of rP4H and 4 mg/kg seed for the rCIα1 (rCIα1-OH in seeds with co-expression of rP4H. High-resolution mass spectrometry (HRMS analysis revealed that nearly half of the collagenous repeating triplets in rCIα1 isolated from rP4H co-expressing maize line had the Pro residues changed to Hyp residues. The HRMS analysis determined the Hyp content of maize-derived rCIα1-OH as 18.11%, which is comparable to the Hyp level of yeast-derived rCIα1-OH (17.47% and the native human CIa1 (14.59%, respectively. The increased Hyp percentage was correlated with a markedly enhanced thermal stability of maize-derived rCIα1-OH when compared to the non-hydroxylated rCIα1. Conclusions This work shows that maize has potential to produce adequately modified exogenous proteins with mammalian-like post-translational modifications that may be require for their use as pharmaceutical and industrial products.

  14. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Cirera Salicio, Susanna; Zhernakova, Daria V.

    2014-01-01

    interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model...... (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P ... the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E-7), and immune-related complications (e.g. Natural killer cell mediated cytotoxity, P = 3.8E-5; B cell receptor signaling pathway, P = 7.2E-5). Lemon-Tree identified three potential regulator genes, using...

  15. Stability analysis of solutions to nonlinear stiff Volterra functional differential equations in Banach spaces

    Institute of Scientific and Technical Information of China (English)

    LI Shoufu

    2005-01-01

    A series of stability, contractivity and asymptotic stability results of the solutions to nonlinear stiff Volterra functional differential equations (VFDEs) in Banach spaces is obtained, which provides the unified theoretical foundation for the stability analysis of solutions to nonlinear stiff problems in ordinary differential equations(ODEs), delay differential equations(DDEs), integro-differential equations(IDEs) and VFDEs of other type which appear in practice.

  16. Analysis of Caputo Impulsive Fractional Order Differential Equations with Applications

    Directory of Open Access Journals (Sweden)

    Lakshman Mahto

    2013-01-01

    Full Text Available We use Sadovskii's fixed point method to investigate the existence and uniqueness of solutions of Caputo impulsive fractional differential equations of order with one example of impulsive logistic model and few other examples as well. We also discuss Caputo impulsive fractional differential equations with finite delay. The results proven are new and compliment the existing one.

  17. Multivariate analysis of regional differentials of nuptiality in Bangladesh.

    Science.gov (United States)

    Chowdhury, A A; Islam, M A

    1981-01-01

    The importance of socioeconomics differentials in nuptiality has occupied a very important position in recent demographic research. An effort has been made in this paper to find out the nature and extent of the causal relationship between the dependent variable--nuptiality, and its determinants. Our findings suggest that education may play a vital role in raising mean age at marriage. This may be done by extending free and compulsory mass and primary education throughout the country. It has further been observed that urbanization through economic development is a precondition to increase the literacy rate and hence female labor force participation in the country's economy. Thus proper education will increase the female employment rate which in turn will raise the age at marriage. Equal distribution of population and insurance schemes for childless couples may also indirectly put a positive effect on nuptiality. Finally, this paper provides a guideline for using the path analysis technique in determining the factors causing the changes and the effects of these factors on nuptiality in Bangladesh. However, caution should be made in taking into account the causal ordering of the indices. Different ordering may give different results.

  18. Differential expression analysis for RNAseq using Poisson mixed models.

    Science.gov (United States)

    Sun, Shiquan; Hood, Michelle; Scott, Laura; Peng, Qinke; Mukherjee, Sayan; Tung, Jenny; Zhou, Xiang

    2017-06-20

    Identifying differentially expressed (DE) genes from RNA sequencing (RNAseq) studies is among the most common analyses in genomics. However, RNAseq DE analysis presents several statistical and computational challenges, including over-dispersed read counts and, in some settings, sample non-independence. Previous count-based methods rely on simple hierarchical Poisson models (e.g. negative binomial) to model independent over-dispersion, but do not account for sample non-independence due to relatedness, population structure and/or hidden confounders. Here, we present a Poisson mixed model with two random effects terms that account for both independent over-dispersion and sample non-independence. We also develop a scalable sampling-based inference algorithm using a latent variable representation of the Poisson distribution. With simulations, we show that our method properly controls for type I error and is generally more powerful than other widely used approaches, except in small samples (n <15) with other unfavorable properties (e.g. small effect sizes). We also apply our method to three real datasets that contain related individuals, population stratification or hidden confounders. Our results show that our method increases power in all three data compared to other approaches, though the power gain is smallest in the smallest sample (n = 6). Our method is implemented in MACAU, freely available at www.xzlab.org/software.html. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Differential network analysis reveals genetic effects on catalepsy modules.

    Directory of Open Access Journals (Sweden)

    Ovidiu D Iancu

    Full Text Available We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS formed by crossing four inbred strains (HS4 and a heterogeneous stock (HS-CC formed from the inbred strain founders of the Collaborative Cross (CC. All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections.

  20. Differential Transcriptome Analysis between Paulownia fortunei and Its Synthesized Autopolyploid

    Directory of Open Access Journals (Sweden)

    Xiaoshen Zhang

    2014-03-01

    Full Text Available Paulownia fortunei is an ecologically and economically important tree species that is widely used as timber and chemical pulp. Its autotetraploid, which carries a number of valuable traits, was successfully induced with colchicine. To identify differences in gene expression between P. fortunei and its synthesized autotetraploid, we performed transcriptome sequencing using an Illumina Genome Analyzer IIx (GAIIx. About 94.8 million reads were generated and assembled into 383,056 transcripts, including 18,984 transcripts with a complete open reading frame. A conducted Basic Local Alignment Search Tool (BLAST search indicated that 16,004 complete transcripts had significant hits in the National Center for Biotechnology Information (NCBI non-redundant database. The complete transcripts were given functional assignments using three public protein databases. One thousand one hundred fifty eight differentially expressed complete transcripts were screened through a digital abundance analysis, including transcripts involved in energy metabolism and epigenetic regulation. Finally, the expression levels of several transcripts were confirmed by quantitative real-time PCR. Our results suggested that polyploidization caused epigenetic-related changes, which subsequently resulted in gene expression variation between diploid and autotetraploid P. fortunei. This might be the main mechanism affected by the polyploidization. Our results represent an extensive survey of the P. fortunei transcriptome and will facilitate subsequent functional genomics research in P. fortunei. Moreover, the gene expression profiles of P. fortunei and its autopolyploid will provide a valuable resource for the study of polyploidization.

  1. Gene co-expression networks shed light into diseases of brain iron accumulation.

    Science.gov (United States)

    Bettencourt, Conceição; Forabosco, Paola; Wiethoff, Sarah; Heidari, Moones; Johnstone, Daniel M; Botía, Juan A; Collingwood, Joanna F; Hardy, John; Milward, Elizabeth A; Ryten, Mina; Houlden, Henry

    2016-03-01

    Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein.

    Science.gov (United States)

    Gargett, Tessa; Grubor-Bauk, Branka; Miller, Darren; Garrod, Tamsin; Yu, Stanley; Wesselingh, Steve; Suhrbier, Andreas; Gowans, Eric J

    2014-06-01

    The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.

  3. Analysis of stability for stochastic delay integro-differential equations.

    Science.gov (United States)

    Zhang, Yu; Li, Longsuo

    2018-01-01

    In this paper, we concern stability of numerical methods applied to stochastic delay integro-differential equations. For linear stochastic delay integro-differential equations, it is shown that the mean-square stability is derived by the split-step backward Euler method without any restriction on step-size, while the Euler-Maruyama method could reproduce the mean-square stability under a step-size constraint. We also confirm the mean-square stability of the split-step backward Euler method for nonlinear stochastic delay integro-differential equations. The numerical experiments further verify the theoretical results.

  4. Power Transformer Differential Protection Based on Neural Network Principal Component Analysis, Harmonic Restraint and Park's Plots

    OpenAIRE

    Tripathy, Manoj

    2012-01-01

    This paper describes a new approach for power transformer differential protection which is based on the wave-shape recognition technique. An algorithm based on neural network principal component analysis (NNPCA) with back-propagation learning is proposed for digital differential protection of power transformer. The principal component analysis is used to preprocess the data from power system in order to eliminate redundant information and enhance hidden pattern of differential current to disc...

  5. Numerical Analysis for Stochastic Partial Differential Delay Equations with Jumps

    OpenAIRE

    Li, Yan; Hu, Junhao

    2013-01-01

    We investigate the convergence rate of Euler-Maruyama method for a class of stochastic partial differential delay equations driven by both Brownian motion and Poisson point processes. We discretize in space by a Galerkin method and in time by using a stochastic exponential integrator. We generalize some results of Bao et al. (2011) and Jacob et al. (2009) in finite dimensions to a class of stochastic partial differential delay equations with jumps in infinite dimensions.

  6. Differential proteome analysis of chikungunya virus infection on host cells.

    Directory of Open Access Journals (Sweden)

    Christina Li-Ping Thio

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach. METHODOLOGY AND PRINCIPAL FINDINGS: The whole cell proteome profiles of CHIKV-infected and mock control WRL-68 cells were compared and analyzed using two-dimensional gel electrophoresis (2-DGE. Fifty-three spots were found to be differentially modulated and 50 were successfully identified by MALDI-TOF/TOF. Eight were significantly up-regulated and 42 were down-regulated. The mRNA expressions of 15 genes were also found to correlate with the corresponding protein expression. STRING network analysis identified several biological processes to be affected, including mRNA processing, translation, energy production and cellular metabolism, ubiquitin-proteasome pathway (UPP and cell cycle regulation. CONCLUSION/SIGNIFICANCE: This study constitutes a first attempt to investigate alteration of the host cellular proteome during early CHIKV infection. Our proteomics data showed that during early infection, CHIKV affected the expression of proteins that are involved in mRNA processing, host metabolic machinery, UPP, and cyclin-dependent kinase 1 (CDK1 regulation (in favour of virus survival, replication and transmission. While results from this study complement the proteomics results obtained from previous late host response studies, functional characterization of these proteins is warranted to reinforce our understanding of their roles during early CHIKV infection in humans.

  7. The analysis of cholescintigraphy in differentiating the causes of jaundice

    International Nuclear Information System (INIS)

    Kim, Jung Gyun; Son, So Yeob; Bae, Kwang Su; Chung, Moo Chan; Choi, Deuk Lin; Kim, Ki Jung

    1985-01-01

    As a adjacent, 99m Tc-IDA complex cholescintigraphy has been used to differentiate the causes of jaundice, hepatocellular jaundice from the obstructive jaundice. So we conducted the retrospective study from the 41 cases of cholescintigraphy from the Mar. 83 to Sept. 84 at the dept. of radiology in the Soonchunhyang university to determine the etiology and differential points in the diagnosing the jaundice. The following results were obtained; 1. As a 1st-ordered parameter, the leading edge hepatic parenchymal transit time was very significant in differentiating the causes of jaundice, among he hepatocellular jaundice, obstructive jaundice due to tumor, and obstructive jaundice due to cholelithiasis. (ρ 2 -test) 2. As a 2nd-ordered parameter, hepatic clearance was very significant in differentiating the hepatocellular jaundice from the jaundice due to partial biliary obstruction. (ρ 2 -test) 4. The difference in bile duct dilatation among the hepatocellular jaundice obstructive jaundice due to tumor, and obstructive jaundice due to cholelithiasis, was significant in differentiating the causes of jaundice. (ρ 2 -test) 5. Intrahepatic stone showed scintigraphic intrahepatic pooling with partial stasis. 6. Cholescintigraphy was useful to differentiated the Rotor's syndrome from the Dubin-Johnson syndrome, supplying the additional criteria

  8. Biomass pyrolysis and combustion integral and differential reaction heats with temperatures using thermogravimetric analysis/differential scanning calorimetry.

    Science.gov (United States)

    Shen, Jiacheng; Igathinathane, C; Yu, Manlu; Pothula, Anand Kumar

    2015-06-01

    Integral reaction heats of switchgrass, big bluestem, and corn stalks were determined using thermogravimetric analysis/differential scanning calorimetry (TGA/DSC). Iso-conversion differential reaction heats using TGA/DSC pyrolysis and combustion of biomass were not available, despite reports available on heats required and released. A concept of iso-conversion differential reaction heats was used to determine the differential reaction heats of each thermal characteristics segment of these materials. Results showed that the integral reaction heats were endothermic from 30 to 700°C for pyrolysis of switchgrass and big bluestem, but they were exothermic for corn stalks prior to 587°C. However, the integral reaction heats for combustion of the materials followed an endothermic to exothermic transition. The differential reaction heats of switchgrass pyrolysis were predominantly endothermic in the fraction of mass loss (0.0536-0.975), and were exothermic for corn stalks (0.0885-0.850) and big bluestem (0.736-0.919). Study results provided better insight into biomass thermal mechanism. Published by Elsevier Ltd.

  9. Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes.

    Science.gov (United States)

    Benz, Karin; Breit, Stephen; Lukoschek, Martin; Mau, Hans; Richter, Wiltrud

    2002-04-26

    This study is intended to optimise expansion and differentiation of cultured human chondrocytes by growth factor application and to identify molecular markers to monitor their differentiation state. We dissected the molecular consequences of matrix release, monolayer, and 3D-alginate culture, growth factor optimised expansion, and re-differentiation protocols by gene expression analysis. Among 19 common cartilage molecules assessed by cDNA array, six proved best to monitor differentiation. Instant down-regulation at release of cells from the matrix was strongest for COL 2A1, fibromodulin, and PRELP while LUM, CHI3L1, and CHI3L2 were expansion-related. Both gene sets reflected the physiologic effects of the most potent growth-inducing (PDGF-BB) and proteoglycan-inducing (BMP-4) factors. Only CRTAC1 expression correlated with 2D/3D switches while the molecular phenotype of native chondrocytes was not restored. The markers and optimised protocols we suggest can help to improve cell therapy of cartilage defects and chondrocyte differentiation from stem cell sources.

  10. Approximate Solutions of Nonlinear Partial Differential Equations by Modified q-Homotopy Analysis Method

    Directory of Open Access Journals (Sweden)

    Shaheed N. Huseen

    2013-01-01

    Full Text Available A modified q-homotopy analysis method (mq-HAM was proposed for solving nth-order nonlinear differential equations. This method improves the convergence of the series solution in the nHAM which was proposed in (see Hassan and El-Tawil 2011, 2012. The proposed method provides an approximate solution by rewriting the nth-order nonlinear differential equation in the form of n first-order differential equations. The solution of these n differential equations is obtained as a power series solution. This scheme is tested on two nonlinear exactly solvable differential equations. The results demonstrate the reliability and efficiency of the algorithm developed.

  11. Genome-wide expression of transcriptomes and their co-expression pattern in subtropical maize (Zea mays L. under waterlogging stress.

    Directory of Open Access Journals (Sweden)

    Nepolean Thirunavukkarasu

    Full Text Available Waterlogging causes extensive damage to maize crops in tropical and subtropical regions. The identification of tolerance genes and their interactions at the molecular level will be helpful to engineer tolerant genotypes. A whole-genome transcriptome assay revealed the specific role of genes in response to waterlogging stress in susceptible and tolerant genotypes. Genes involved in the synthesis of ethylene and auxin, cell wall metabolism, activation of G-proteins and formation of aerenchyma and adventitious roots, were upregulated in the tolerant genotype. Many transcription factors, particularly ERFs, MYB, HSPs, MAPK, and LOB-domain protein were involved in regulation of these traits. Genes responsible for scavenging of ROS generated under stress were expressed along with those involved in carbohydrate metabolism. The physical locations of 21 genes expressed in the tolerant genotype were found to correspond with the marker intervals of known QTLs responsible for development of adaptive traits. Among the candidate genes, most showed synteny with genes of sorghum and foxtail millet. Co-expression analysis of 528 microarray samples including 16 samples from the present study generated seven functional modules each in the two genotypes, with differing characteristics. In the tolerant genotype, stress genes were co-expressed along with peroxidase and fermentation pathway genes.

  12. Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells

    OpenAIRE

    Zhou Qing; Plath Kathrin; Fan Guoping; Mason Mike J; Horvath Steve

    2009-01-01

    Abstract Background Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we...

  13. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

    OpenAIRE

    DeYoung Joseph; Langfelder Peter; Fuller Tova F; Blauw Hylke M; van Es Michael A; van Vught Paul WJ; Horvath Steve; Saris Christiaan GJ; Wokke John HJ; Veldink Jan H; van den Berg Leonard H; Ophoff Roel A

    2009-01-01

    Abstract Background Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in...

  14. Co-expression of putative stemness and epithelial-to-mesenchymal transition markers on single circulating tumour cells from patients with early and metastatic breast cancer.

    Science.gov (United States)

    Papadaki, Maria A; Kallergi, Galatea; Zafeiriou, Zafeiris; Manouras, Lefteris; Theodoropoulos, Panayiotis A; Mavroudis, Dimitris; Georgoulias, Vassilis; Agelaki, Sofia

    2014-09-03

    The detection of circulating tumor cells (CTCs) in peripheral blood (PB) of patients with breast cancer predicts poor clinical outcome. Cancer cells with stemness and epithelial-to-mesenchymal transition (EMT) features display enhanced malignant and metastatic potential. A new methodology was developed in order to investigate the co-expression of a stemness and an EMT marker (ALDH1 and TWIST, respectively) on single CTCs of patients with early and metastatic breast cancer. Triple immunofluorescence using anti-pancytokeratin (A45-B/B3), anti-ALDH1 and anti-TWIST antibodies was performed in cytospins prepared from hepatocellular carcinoma HepG2 cells and SKBR-3, MCF-7 and MDA.MB.231 breast cancer cell lines. Evaluation of ALDH1 expression levels (high, low or absent) and TWIST subcellular localization (nuclear, cytoplasmic or absent) was performed using the ARIOL system. Cytospins prepared from peripheral blood of patients with early (n = 80) and metastatic (n = 50) breast cancer were analyzed for CTC detection (based on pan-cytokeratin expression and cytomorphological criteria) and characterized according to ALDH1 and TWIST. CTCs were detected in 13 (16%) and 25 (50%) patients with early and metastatic disease, respectively. High ALDH1 expression (ALDH1high) and nuclear TWIST localization (TWISTnuc) on CTCs was confirmed in more patients with metastatic than early breast cancer (80% vs. 30.8%, respectively; p = 0.009). In early disease, ALDH1low/neg CTCs (p = 0.006) and TWISTcyt/neg CTCs (p = 0.040) were mainly observed. Regarding co-expression of these markers, ALDH1high/TWISTnuc CTCs were more frequently evident in the metastatic setting (76% vs. 15.4% of patients, p = 0.001; 61.5% vs. 12.9% of total CTCs), whereas in early disease ALDH1low/neg/TWISTcyt/neg CTCs were mainly detected (61.5% vs. 20% of patients, p = 0.078; 41.9% vs. 7.7% of total CTCs). A new assay is provided for the evaluation of ALDH1 and TWIST co-expression at the

  15. International Winter Workshop on Differential Equations and Numerical Analysis

    CERN Document Server

    Miller, John; Narasimhan, Ramanujam; Mathiazhagan, Paramasivam; Victor, Franklin

    2016-01-01

    This book offers an ideal introduction to singular perturbation problems, and a valuable guide for researchers in the field of differential equations. It also includes chapters on new contributions to both fields: differential equations and singular perturbation problems. Written by experts who are active researchers in the related fields, the book serves as a comprehensive source of information on the underlying ideas in the construction of numerical methods to address different classes of problems with solutions of different behaviors, which will ultimately help researchers to design and assess numerical methods for solving new problems. All the chapters presented in the volume are complemented by illustrations in the form of tables and graphs.

  16. G-NEST: A gene neighborhood scoring tool to identify co-conserved, co-expressed genes

    Science.gov (United States)

    In previous studies, gene neighborhoods--spatial clusters of co-expressed genes in the genome--have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Sc...

  17. MIDBRAIN CATECHOLAMINERGIC NEURONS CO-EXPRESS α-SYNUCLEIN AND TAU IN PROGRESSIVE SUPRANUCLEAR PALSY

    Directory of Open Access Journals (Sweden)

    María Elena eErro Aguirre

    2015-03-01

    Full Text Available Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP.Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients’ clinical symptoms were retrospectively recorded. Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs were only found in two PSP cases (8% that fulfilled the clinical subtype of PSP known as Richardson’s syndrome (RS. LBs were present in the locus ceruleus, substantia nigra pars compacta, basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson’s disease. Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase-positive neurons of the locus ceruleus and substantia nigra pars compacta.Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as ‘misfolded protein diseases’.

  18. Interactions between co-expressed Arabidopsis sucrose transporters in the split-ubiquitin system

    Directory of Open Access Journals (Sweden)

    Lalonde Sylvie

    2003-03-01

    Full Text Available Abstract Background The Arabidopsis genome contains nine sucrose transporter paralogs falling into three clades: SUT1-like, SUT2 and SUT4. The carriers differ in their kinetic properties. Many transport proteins are known to exist as oligomers. The yeast-based split ubiquitin system can be used to analyze the ability of membrane proteins to interact. Results Promoter-GUS fusions were used to analyze the cellular expression of the three transporter genes in transgenic Arabidopsis plants. All three fusion genes are co-expressed in companion cells. Protein-protein interactions between Arabidopsis sucrose transporters were tested using the split ubiquitin system. Three paralogous sucrose transporters are capable of interacting as either homo- or heteromers. The interactions are specific, since a potassium channel and a glucose transporter did not show interaction with sucrose transporters. Also the biosynthetic and metabolizing enzymes, sucrose phosphate phosphatase and sucrose synthase, which were found to be at least in part bound to the plasma membrane, did not specifically interact with sucrose transporters. Conclusions The split-ubiquitin system provides a powerful tool to detect potential interactions between plant membrane proteins by heterologous expression in yeast, and can be used to screen for interactions with membrane proteins as baits. Like other membrane proteins, the Arabidopsis sucrose transporters are able to form oligomers. The biochemical approaches are required to confirm the in planta interaction.

  19. Co-expression and characterization of enterocin CRL35 and its mutant in Escherichia coli Rosetta

    Directory of Open Access Journals (Sweden)

    Masías Emilse

    2014-01-01

    Full Text Available Even though many sequences and structures of bacteriocins from lactic acid bacteria have been fully characterized so far, little information is currently available about bacteriocins heterologously produced by Escherichia coli. For this purpose, the structural gene of enterocin CRL35, munA, was PCR-amplified using specific primers and cloned downstream of PelB sequence in the pET22b (+ expression vector. E. coli Rosetta (DE3 pLysS was chosen as the host for production and enterocin was purified by an easy two-step protocol. The bacteriocin was correctly expressed with the expected intramolecular disulfide bond. Nevertheless, it was found that a variant of the enterocin, differing by 12 Da from the native polypeptide, was co-expressed by E. coli Rosetta in comparable amount. Indeed, the mutant bacteriocin contained two amino acid substitutions that were characterized by matrix assisted laser desorption ionization-time of flight (MALDI-TOF and HPLCelectrospray (ESI-Q-TOF tandem mass spectrometry (MS/ MS sequencing. This is the first report regarding the production of mutants of pediocin-like bacteriocins in the E. coli expression system.

  20. Immunohistochemical Observation of Co-expression of E- and N-cadherins in Rat Organogenesis

    International Nuclear Information System (INIS)

    Sakamoto, Atsushi; Murata, Kazumoto; Suzuki, Hideto; Yatabe, Megumi; Kikuchi, Motoshi

    2008-01-01

    Cadherins are a family of transmembrane glycoproteins that mediate cell-to-cell adhesion. Isoforms, including E- and N-cadherin, have been identified and shown to regulate morphogenesis through homophilic binding. In the ontogeny, the expressions of E- and N-cadherin change spatiotemporally, and the changes in cadherin isoforms, called cadherin switching, impact the mechanical adhesion of cells. Furthermore, cadherin functions as a receptor that transfers information from outside to inside cells, and in terms of switching, it affects cell phenotypes. To observe the expression patterns of E- and N-cadherins during embryogenesis and to identify cells that transiently coexpress both cadherins, we employed a recently developed immunohistochemical double staining technique in rat fetuses. At embryonic day 9, embryonic ectodermal cells more dominantly expressed E-cadherin, while mesodermal cells more dominantly expressed N-cadherin. At embryonic day 10, the expression pattern of E-cadherin in the surface ectoderm and endoderm and that of N-cadherin in the neuroectoderm were established. After embryonic day 10, unique co-expression of E- and N-cadherin was observed in primordia, such as the bulbus cordis, otic pit, notochord, and Rathke’s pouch. In the present study, it was possible to visualize the expression patterns of E- and N-cadherin during early fetal development, which enabled us to morphologically clarify cadherin switching

  1. Analysis of the essential spectrum of singular matrix differential operators

    Czech Academy of Sciences Publication Activity Database

    Ibrogimov, O. O.; Siegl, Petr; Tretter, C.

    2016-01-01

    Roč. 260, č. 4 (2016), s. 3881-3926 ISSN 0022-0396 Institutional support: RVO:61389005 Key words : essential spectrum * system of singular differential equations * operator matrix * Schur complement * magnetohydrodynamics * Stellar equilibrium model Subject RIV: BE - Theoretical Physics Impact factor: 1.988, year: 2016

  2. Stability analysis of a class of fractional delay differential equations

    Indian Academy of Sciences (India)

    Abstract. In this paper we analyse stability of nonlinear fractional order delay differential equa- tions of the form Dα y(t) = af (y(t − τ )) − by(t), where Dα is a Caputo fractional derivative of order 0 < α ≤ 1. We describe stability regions using critical curves. To explain the proposed theory, we discuss fractional order logistic ...

  3. Stability analysis of a class of fractional delay differential equations

    Indian Academy of Sciences (India)

    In this paper we analyse stability of nonlinear fractional order delay differential equations of the form D y ( t ) = a f ( y ( t − ) ) − by ( t ) , where D is a Caputo fractional derivative of order 0 < ≤ 1. We describe stability regions using critical curves. To explain the proposed theory, we discuss fractional order logistic ...

  4. Thermogravimetric and differential thermal analysis of potassium bicarbonate contaminated cellulose

    Science.gov (United States)

    A. Broido

    1966-01-01

    When samples undergo a complicated set of simultaneous and sequential reactions, as cellulose does on heating, results of thermogravimetric and differential thermal analyses are difficult to interpret. Nevertheless, careful comparison of pure and contaminated samples, pyrolyzed under identical conditions, can yield useful information. In these experiments TGA and DTA...

  5. A Comparative Analysis of Fertility Differentials in Ghana and Nigeria

    African Journals Online (AJOL)

    AJRH Managing Editor

    Our study compared the two countries' fertility levels and their determinants as well as the differentials in ... The sample of 33,385 and 4,916 women aged 15-49 years obtained in Nigeria and Ghana respectively was ... poverty at both the household and national levels1- ... China, India, United States, Indonesia, Brazil, and.

  6. In vivo modification of tyrosine residues in recombinant mussel adhesive protein by tyrosinase co-expression in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Choi Yoo

    2012-10-01

    Full Text Available Abstract Background In nature, mussel adhesive proteins (MAPs show remarkable adhesive properties, biocompatibility, and biodegradability. Thus, they have been considered promising adhesive biomaterials for various biomedical and industrial applications. However, limited production of natural MAPs has hampered their practical applications. Recombinant production in bacterial cells could be one alternative to obtain useable amounts of MAPs, although additional post-translational modification of tyrosine residues into 3,4-dihydroxyphenyl-alanine (Dopa and Dopaquinone is required. The superior properties of MAPs are mainly attributed to the introduction of quinone-derived intermolecular cross-links. To solve this problem, we utilized a co-expression strategy of recombinant MAP and tyrosinase in Escherichia coli to successfully modify tyrosine residues in vivo. Results A recombinant hybrid MAP, fp-151, was used as a target for in vivo modification, and a dual vector system of pET and pACYC-Duet provided co-expression of fp-151 and tyrosinase. As a result, fp-151 was over-expressed and mainly obtained from the soluble fraction in the co-expression system. Without tyrosinase co-expression, fp-151 was over-expressed in an insoluble form in inclusion bodies. The modification of tyrosine residues in the soluble-expressed fp-151 was clearly observed from nitroblue tetrazolium staining and liquid-chromatography-mass/mass spectrometry analyses. The purified, in vivo modified, fp-151 from the co-expression system showed approximately 4-fold higher bulk-scale adhesive strength compared to in vitro tyrosinase-treated fp-151. Conclusion Here, we reported a co-expression system to obtain in vivo modified MAP; additional in vitro tyrosinase modification was not needed to obtain adhesive properties and the in vivo modified MAP showed superior adhesive strength compared to in vitro modified protein. It is expected that this co-expression strategy will accelerate

  7. Partial differential equations with variable exponents variational methods and qualitative analysis

    CERN Document Server

    Radulescu, Vicentiu D

    2015-01-01

    Partial Differential Equations with Variable Exponents: Variational Methods and Qualitative Analysis provides researchers and graduate students with a thorough introduction to the theory of nonlinear partial differential equations (PDEs) with a variable exponent, particularly those of elliptic type. The book presents the most important variational methods for elliptic PDEs described by nonhomogeneous differential operators and containing one or more power-type nonlinearities with a variable exponent. The authors give a systematic treatment of the basic mathematical theory and constructive meth

  8. Genome-wide targeted prediction of ABA responsive genes in rice based on over-represented cis-motif in co-expressed genes.

    Science.gov (United States)

    Lenka, Sangram K; Lohia, Bikash; Kumar, Abhay; Chinnusamy, Viswanathan; Bansal, Kailash C

    2009-02-01

    Abscisic acid (ABA), the popular plant stress hormone, plays a key role in regulation of sub-set of stress responsive genes. These genes respond to ABA through specific transcription factors which bind to cis-regulatory elements present in their promoters. We discovered the ABA Responsive Element (ABRE) core (ACGT) containing CGMCACGTGB motif as over-represented motif among the promoters of ABA responsive co-expressed genes in rice. Targeted gene prediction strategy using this motif led to the identification of 402 protein coding genes potentially regulated by ABA-dependent molecular genetic network. RT-PCR analysis of arbitrarily chosen 45 genes from the predicted 402 genes confirmed 80% accuracy of our prediction. Plant Gene Ontology (GO) analysis of ABA responsive genes showed enrichment of signal transduction and stress related genes among diverse functional categories.

  9. Stochastic fractional differential equations: Modeling, method and analysis

    International Nuclear Information System (INIS)

    Pedjeu, Jean-C.; Ladde, Gangaram S.

    2012-01-01

    By introducing a concept of dynamic process operating under multi-time scales in sciences and engineering, a mathematical model described by a system of multi-time scale stochastic differential equations is formulated. The classical Picard–Lindelöf successive approximations scheme is applied to the model validation problem, namely, existence and uniqueness of solution process. Naturally, this leads to the problem of finding closed form solutions of both linear and nonlinear multi-time scale stochastic differential equations of Itô–Doob type. Finally, to illustrate the scope of ideas and presented results, multi-time scale stochastic models for ecological and epidemiological processes in population dynamic are outlined.

  10. Analysis of E2F factors during epidermal differentiation.

    Science.gov (United States)

    Chang, Wing Y; Dagnino, Lina

    2005-01-01

    The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

  11. Partial wave analysis for folded differential cross sections

    Science.gov (United States)

    Machacek, J. R.; McEachran, R. P.

    2018-03-01

    The value of modified effective range theory (MERT) and the connection between differential cross sections and phase shifts in low-energy electron scattering has long been recognized. Recent experimental techniques involving magnetically confined beams have introduced the concept of folded differential cross sections (FDCS) where the forward (θ ≤ π/2) and backward scattered (θ ≥ π/2) projectiles are unresolved, that is the value measured at the angle θ is the sum of the signal for particles scattered into the angles θ and π - θ. We have developed an alternative approach to MERT in order to analyse low-energy folded differential cross sections for positrons and electrons. This results in a simplified expression for the FDCS when it is expressed in terms of partial waves and thereby enables one to extract the first few phase shifts from a fit to an experimental FDCS at low energies. Thus, this method predicts forward and backward angle scattering (0 to π) using only experimental FDCS data and can be used to determine the total elastic cross section solely from experimental results at low-energy, which are limited in angular range.

  12. A stochastic differential equation analysis of cerebrospinal fluid dynamics.

    Science.gov (United States)

    Raman, Kalyan

    2011-01-18

    Clinical measurements of intracranial pressure (ICP) over time show fluctuations around the deterministic time path predicted by a classic mathematical model in hydrocephalus research. Thus an important issue in mathematical research on hydrocephalus remains unaddressed--modeling the effect of noise on CSF dynamics. Our objective is to mathematically model the noise in the data. The classic model relating the temporal evolution of ICP in pressure-volume studies to infusions is a nonlinear differential equation based on natural physical analogies between CSF dynamics and an electrical circuit. Brownian motion was incorporated into the differential equation describing CSF dynamics to obtain a nonlinear stochastic differential equation (SDE) that accommodates the fluctuations in ICP. The SDE is explicitly solved and the dynamic probabilities of exceeding critical levels of ICP under different clinical conditions are computed. A key finding is that the probabilities display strong threshold effects with respect to noise. Above the noise threshold, the probabilities are significantly influenced by the resistance to CSF outflow and the intensity of the noise. Fluctuations in the CSF formation rate increase fluctuations in the ICP and they should be minimized to lower the patient's risk. The nonlinear SDE provides a scientific methodology for dynamic risk management of patients. The dynamic output of the SDE matches the noisy ICP data generated by the actual intracranial dynamics of patients better than the classic model used in prior research.

  13. A stochastic differential equation analysis of cerebrospinal fluid dynamics

    Directory of Open Access Journals (Sweden)

    Raman Kalyan

    2011-01-01

    Full Text Available Abstract Background Clinical measurements of intracranial pressure (ICP over time show fluctuations around the deterministic time path predicted by a classic mathematical model in hydrocephalus research. Thus an important issue in mathematical research on hydrocephalus remains unaddressed--modeling the effect of noise on CSF dynamics. Our objective is to mathematically model the noise in the data. Methods The classic model relating the temporal evolution of ICP in pressure-volume studies to infusions is a nonlinear differential equation based on natural physical analogies between CSF dynamics and an electrical circuit. Brownian motion was incorporated into the differential equation describing CSF dynamics to obtain a nonlinear stochastic differential equation (SDE that accommodates the fluctuations in ICP. Results The SDE is explicitly solved and the dynamic probabilities of exceeding critical levels of ICP under different clinical conditions are computed. A key finding is that the probabilities display strong threshold effects with respect to noise. Above the noise threshold, the probabilities are significantly influenced by the resistance to CSF outflow and the intensity of the noise. Conclusions Fluctuations in the CSF formation rate increase fluctuations in the ICP and they should be minimized to lower the patient's risk. The nonlinear SDE provides a scientific methodology for dynamic risk management of patients. The dynamic output of the SDE matches the noisy ICP data generated by the actual intracranial dynamics of patients better than the classic model used in prior research.

  14. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    Science.gov (United States)

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Multiscale differential phase contrast analysis with a unitary detector

    KAUST Repository

    Lopatin, Sergei; Ivanov, Yurii P.; Kosel, Jü rgen; Chuvilin, Andrey

    2015-01-01

    A new approach to generate differential phase contrast (DPC) images for the visualization and quantification of local magnetic fields in a wide range of modern nano materials is reported. In contrast to conventional DPC methods our technique utilizes the idea of a unitary detector under bright field conditions, making it immediately usable by a majority of modern transmission electron microscopes. The approach is put on test to characterize the local magnetization of cylindrical nanowires and their 3D ordered arrays, revealing high sensitivity of our method in a combination with nanometer-scale spatial resolution.

  16. Introduction to stochastic analysis integrals and differential equations

    CERN Document Server

    Mackevicius, Vigirdas

    2013-01-01

    This is an introduction to stochastic integration and stochastic differential equations written in an understandable way for a wide audience, from students of mathematics to practitioners in biology, chemistry, physics, and finances. The presentation is based on the naïve stochastic integration, rather than on abstract theories of measure and stochastic processes. The proofs are rather simple for practitioners and, at the same time, rather rigorous for mathematicians. Detailed application examples in natural sciences and finance are presented. Much attention is paid to simulation diffusion pro

  17. Multiscale differential phase contrast analysis with a unitary detector

    KAUST Repository

    Lopatin, Sergei

    2015-12-30

    A new approach to generate differential phase contrast (DPC) images for the visualization and quantification of local magnetic fields in a wide range of modern nano materials is reported. In contrast to conventional DPC methods our technique utilizes the idea of a unitary detector under bright field conditions, making it immediately usable by a majority of modern transmission electron microscopes. The approach is put on test to characterize the local magnetization of cylindrical nanowires and their 3D ordered arrays, revealing high sensitivity of our method in a combination with nanometer-scale spatial resolution.

  18. SYNTHETIC ANALYSIS OF INDICATORS USED IN THE ANALYSIS OF PRODUCT QUALITY DIFFERENTIATED AND NON-DIFFERENTIATED ON QUALITY CLASSES

    Directory of Open Access Journals (Sweden)

    ECOBICI MIHAELA LOREDANA

    2016-12-01

    Full Text Available Product quality has been and will remain one of the most important indicators of increasing economic and financial performance of a company. Quality is that which ensures the greatest part of the competitiveness of a product or service, this being the result of some important aspects such as: products and services of quality to meet consumers requirements, low costs without affecting the quality level, the performance of contractual obligations, customer satisfaction and last but not least obtaining profit. Research and results concerning this issue will result in the prerequisites in the process for quality assurance that can develop both internally and externally. The purpose of this article lies in the approach and illustration of the aspects of products differentiated and non-differentiated in quality classes. In launching this research I will try to highlight some aspects that most efficiently the indicators mentioned above, indicators that read to what extent a certain product meets the characteristics specified to its destination.

  19. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  20. Analysis of a ferrofluid core differential transformer tilt measurement sensor

    Energy Technology Data Exchange (ETDEWEB)

    Medvegy, T.; Molnár, Á.; Molnár, G.; Gugolya, Z.

    2017-04-15

    In our work, we developed a ferrofluid core differential transformer sensor, which can be used to measure tilt and acceleration. The proposed sensor consisted of three coils, from which the primary was excited with an alternating current. In the space surrounded by the coils was a cell half-filled with ferrofluid, therefore in the horizontal state of the sensor the fluid distributes equally in the three sections of the cell surrounded by the three coils. Nevertheless when the cell is being tilted or accelerated (in the direction of the axis of the coils), there is a different amount of ferrofluid in the three sections. The voltage induced in the secondary coils strongly depends on the amount of ferrofluid found in the core surrounded by them, so the tilt or the acceleration of the cell becomes measurable. We constructed the sensor in several layouts. The linearly coiled sensor had an excellent resolution. Another version with a toroidal cell had almost perfect linearity and a virtually infinite measuring range. - Highlights: • A ferrofluid core differential transformer can be used to measure tilt. • The theoretical description of two different type of the sensor is introduced. • The measuring range, and the sensitivity depends on the dimensions of the sensor.

  1. A novel joint analysis framework improves identification of differentially expressed genes in cross disease transcriptomic analysis

    Directory of Open Access Journals (Sweden)

    Wenyi Qin

    2018-02-01

    Full Text Available Abstract Motivation Detecting differentially expressed (DE genes between disease and normal control group is one of the most common analyses in genome-wide transcriptomic data. Since most studies don’t have a lot of samples, researchers have used meta-analysis to group different datasets for the same disease. Even then, in many cases the statistical power is still not enough. Taking into account the fact that many diseases share the same disease genes, it is desirable to design a statistical framework that can identify diseases’ common and specific DE genes simultaneously to improve the identification power. Results We developed a novel empirical Bayes based mixture model to identify DE genes in specific study by leveraging the shared information across multiple different disease expression data sets. The effectiveness of joint analysis was demonstrated through comprehensive simulation studies and two real data applications. The simulation results showed that our method consistently outperformed single data set analysis and two other meta-analysis methods in identification power. In real data analysis, overall our method demonstrated better identification power in detecting DE genes and prioritized more disease related genes and disease related pathways than single data set analysis. Over 150% more disease related genes are identified by our method in application to Huntington’s disease. We expect that our method would provide researchers a new way of utilizing available data sets from different diseases when sample size of the focused disease is limited.

  2. Characterization of oriented cracks with differential strain analysis

    International Nuclear Information System (INIS)

    Siegfried, R.; Simmons, G.

    1978-01-01

    Linear strain of a rock sample as a function of hydrostatic pressure can be measured with a precision of 2 x 10 -6 . Such high-precision data for three orthogonal directions allow calculation of the distribution function for the porosity due to cracks closing completely at a given pressure. Such data for at least six independent directions yield the zero-pressure strain tensor due to cracks closing completely at a given pressure. The principal values and axes of this tensor distribution function provide information about the orientation of cracks as a function of closure pressure. In this manuscript we first develop the mathematical basis for the technique and then illustrate it with differential strain data for two samples, the Westerly (Rhode Island) granite and the Twin Sisters (Washington) dunite. Strain tensor calculations reveal that each of these samples has a different type of anisotropic crack distribution

  3. Multilayered analog optical differentiating device: performance analysis on structural parameters.

    Science.gov (United States)

    Wu, Wenhui; Jiang, Wei; Yang, Jiang; Gong, Shaoxiang; Ma, Yungui

    2017-12-15

    Analogy optical devices (AODs) able to do mathematical computations have recently gained strong research interest for their potential applications as accelerating hardware in traditional electronic computers. The performance of these wavefront-processing devices is primarily decided by the accuracy of the angular spectral engineering. In this Letter, we show that the multilayer technique could be a promising method to flexibly design AODs according to the input wavefront conditions. As examples, various Si-SiO 2 -based multilayer films are designed that can precisely perform the second-order differentiation for the input wavefronts of different Fourier spectrum widths. The minimum number and thickness uncertainty of sublayers for the device performance are discussed. A technique by rescaling the Fourier spectrum intensity has been proposed in order to further improve the practical feasibility. These results are thought to be instrumental for the development of AODs.

  4. MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4

    OpenAIRE

    Hong, Candice Sun; Graham, Nicholas A.; Gu, Wen; Espindola Camacho, Carolina; Mah, Vei; Maresh, Erin L.; Alavi, Mohammed; Bagryanova, Lora; Krotee, Pascal A.L.; Gardner, Brian K.; Behbahan, Iman Saramipoor; Horvath, Steve; Chia, David; Mellinghoff, Ingo K.; Hurvitz, Sara A.

    2016-01-01

    Monocarboxylate Transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but ...

  5. Systematic comparison of co-expression of multiple recombinant thermophilic enzymes in Escherichia coli BL21(DE3).

    Science.gov (United States)

    Chen, Hui; Huang, Rui; Zhang, Y-H Percival

    2017-06-01

    The precise control of multiple heterologous enzyme expression levels in one Escherichia coli strain is important for cascade biocatalysis, metabolic engineering, synthetic biology, natural product synthesis, and studies of complexed proteins. We systematically investigated the co-expression of up to four thermophilic enzymes (i.e., α-glucan phosphorylase (αGP), phosphoglucomutase (PGM), glucose 6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH)) in E. coli BL21(DE3) by adding T7 promoter or T7 terminator of each gene for multiple genes in tandem, changing gene alignment, and comparing one or two plasmid systems. It was found that the addition of T7 terminator after each gene was useful to decrease the influence of the upstream gene. The co-expression of the four enzymes in E. coli BL21(DE3) was demonstrated to generate two NADPH molecules from one glucose unit of maltodextrin, where NADPH was oxidized to convert xylose to xylitol. The best four-gene co-expression system was based on two plasmids (pET and pACYC) which harbored two genes. As a result, apparent enzymatic activities of the four enzymes were regulated to be at similar levels and the overall four-enzyme activity was the highest based on the formation of xylitol. This study provides useful information for the precise control of multi-enzyme-coordinated expression in E. coli BL21(DE3).

  6. ADAGE signature analysis: differential expression analysis with data-defined gene sets.

    Science.gov (United States)

    Tan, Jie; Huyck, Matthew; Hu, Dongbo; Zelaya, René A; Hogan, Deborah A; Greene, Casey S

    2017-11-22

    Gene set enrichment analysis and overrepresentation analyses are commonly used methods to determine the biological processes affected by a differential expression experiment. This approach requires biologically relevant gene sets, which are currently curated manually, limiting their availability and accuracy in many organisms without extensively curated resources. New feature learning approaches can now be paired with existing data collections to directly extract functional gene sets from big data. Here we introduce a method to identify perturbed processes. In contrast with methods that use curated gene sets, this approach uses signatures extracted from public expression data. We first extract expression signatures from public data using ADAGE, a neural network-based feature extraction approach. We next identify signatures that are differentially active under a given treatment. Our results demonstrate that these signatures represent biological processes that are perturbed by the experiment. Because these signatures are directly learned from data without supervision, they can identify uncurated or novel biological processes. We implemented ADAGE signature analysis for the bacterial pathogen Pseudomonas aeruginosa. For the convenience of different user groups, we implemented both an R package (ADAGEpath) and a web server ( http://adage.greenelab.com ) to run these analyses. Both are open-source to allow easy expansion to other organisms or signature generation methods. We applied ADAGE signature analysis to an example dataset in which wild-type and ∆anr mutant cells were grown as biofilms on the Cystic Fibrosis genotype bronchial epithelial cells. We mapped active signatures in the dataset to KEGG pathways and compared with pathways identified using GSEA. The two approaches generally return consistent results; however, ADAGE signature analysis also identified a signature that revealed the molecularly supported link between the MexT regulon and Anr. We designed

  7. Calculation and Analysis of Differential Corrections for BeiDou

    Science.gov (United States)

    Yang, Sainan; Chen, Junping; Zhang, Yize

    2015-04-01

    BeiDou Satellite Navigation System has been providing service forAsia-Pacific area. BeiDou uses observations of regional monitoring network to determine satellite orbit, which limits the satellite orbit accuracy. And the satellite clock error is produced by time synchronization system. The time synchronization delay of antenna device is general obtained through prior Calibration, and the residual calibration error is included in the satellite clock, which affects the prediction accuracy of satellite clock error. In this paper, we study the algorithms of Beidou differential corrections to improve the accuracy of satellite signals to improve the user positioning accuracy. In this algorithm, both pseudo-range and phase observations are used to calculate differential corrections. We process pseudo-range observations to obtain equivalent satellite clock error, which include satellite clock errors and orbit radial errors, as well as the average projection of orbit tangential and normal errors in combination. And the epoch-difference of phase observations are processed to eliminate the ambiguity which simplifies algorithms and ensure the relative accuracy (corrections variety between the epochs). Observations more than 10 stations in China are processed, and the equivalent clock error calculation results are analyzed, which shows that the satellite UDRE are significantly reduced and user location accuracy improves when the equivalent clock error corrections are applied. The residuals deducting equivalent satellite clock error contains the projection difference of satellite orbit error in all station (tangential and normal errors are main). We utilize the residuals to solve the tangential and normal orbit errors which cause the projection difference. The same observation data is processed. The results show that after calculating three-dimensional corrections, the satellite UDRE doesn't improve significantly compared to equivalent satellite clock error corrections and user

  8. Characterization of differentially expressed genes involved in pathways associated with gastric cancer.

    Directory of Open Access Journals (Sweden)

    Hao Li

    Full Text Available To explore the patterns of gene expression in gastric cancer, a total of 26 paired gastric cancer and noncancerous tissues from patients were enrolled for gene expression microarray analyses. Limma methods were applied to analyze the data, and genes were considered to be significantly differentially expressed if the False Discovery Rate (FDR value was 2. Subsequently, Gene Ontology (GO categories were used to analyze the main functions of the differentially expressed genes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG database, we found pathways significantly associated with the differential genes. Gene-Act network and co-expression network were built respectively based on the relationships among the genes, proteins and compounds in the database. 2371 mRNAs and 350 lncRNAs considered as significantly differentially expressed genes were selected for the further analysis. The GO categories, pathway analyses and the Gene-Act network showed a consistent result that up-regulated genes were responsible for tumorigenesis, migration, angiogenesis and microenvironment formation, while down-regulated genes were involved in metabolism. These results of this study provide some novel findings on coding RNAs, lncRNAs, pathways and the co-expression network in gastric cancer which will be useful to guide further investigation and target therapy for this disease.

  9. Proteomic analysis of PC12 cell differentiation induced by ionizing radiation

    International Nuclear Information System (INIS)

    Zhang Junquan; Gao Ronglian; Chen Xiaohua; Wang Zhidong; Dong Bo; Rao Yalan; Hou Lili; Zhang Hao; Mao Bingzhi

    2005-01-01

    Objective: To explore the molecular mechanism of PC12 cell differentiation induced by ionizing radiation and screen the molecular target of nervous system injured by irradiation. Methods: PC12 cells were irradiated with 16 Gy 60 Co γ ray. Total proteins of normal and irradiated cells were prepared 48 hours after irradiation and separated with two dimensional gel electrophoresis. Some differential expressed proteins were characterized with mass spectrometry. Results: 876 differential expressed proteins were observed. Up-regulated expression of ubiquitin carboxyl-terminal hydratase L1 was found. Down-regulated expression of new protein similar to HP1α was found. Conclusion: The characterization of some differential expressed proteins through proteomic analysis would benefit the research of molecular mechanism of PC12 cell differentiation induced by ionizing radiation. (authors)

  10. Integrator Performance Analysis In Solving Stiff Differential Equation System

    International Nuclear Information System (INIS)

    B, Alhadi; Basaruddin, T.

    2001-01-01

    In this paper we discuss the four-stage index-2 singly diagonally implicit Runge-Kutta method, which is used to solve stiff ordinary differential equations (SODE). Stiff problems require a method where step size is not restricted by the method's stability. We desire SDIRK to be A-stable that has no stability restrictions when solving y'= λy with Reλ>0 and h>0, so by choosing suitable stability function we can determine appropriate constant g) to formulate SDIRK integrator to solve SODE. We select the second stage of the internal stage as embedded method to perform low order estimate for error predictor. The strategy for choosing the step size is adopted from the strategy proposed by Hall(1996:6). And the algorithm that is developed in this paper is implemented using MATLAB 5.3, which is running on Window's 95 environment. Our performance measurement's local truncation error accuracy, and efficiency were evaluated by statistical results of sum of steps, sum of calling functions, average of Newton iterations and elapsed times.As the results, our numerical experiment show that SDIRK is unconditionally stable. By using Hall's step size strategy, the method can be implemented efficiently, provided that suitable parameters are used

  11. Particle analysis and differentiation using a photovoltaic cell

    International Nuclear Information System (INIS)

    Fu, Lung-Ming; Shu, Wei-En; Wang, Yao-Nan

    2012-01-01

    A method is proposed for the sizing and counting of fluorescent and non-fluorescent particles of various sizes on a poly-dimethylsiloxane microchip. In the proposed approach, the detection region of the microchip is illuminated by a laser, which is then incident on a power-free photovoltaic cell. As the particles (both fluorescent and non-fluorescent) pass through the detection region, they block the laser beam, causing a reduction in the output voltage of the cell. The voltage signal is interfaced to a PC and is used to determine both the size and the number of the particles. Meanwhile, the fluorescence signal generated by the fluorescent particles within the sample is detected by an avalanche photodetector and is used to differentiate between the fluorescent and non-fluorescent particles in the sample. The effectiveness of the proposed approach is demonstrated using fluorescent-labeled beads with means diameters of 5, 8 and 10 µm, respectively, and unlabeled beads with a mean diameter of 7.2 µm. The experimental results confirm that the forward scattered light signal generated by the photovoltaic cell enables both the size and the number of the particles to be reliably determined. Moreover, it is shown that the number of non-fluorescent particles within the sample can be easily determined by comparing the signals received from the photovoltaic cell and avalanche photodetector, respectively. (paper)

  12. Spectral analysis of difference and differential operators in weighted spaces

    International Nuclear Information System (INIS)

    Bichegkuev, M S

    2013-01-01

    This paper is concerned with describing the spectrum of the difference operator K:l α p (Z,X)→l α p (Z......athscrKx)(n)=Bx(n−1),  n∈Z,  x∈l α p (Z,X), with a constant operator coefficient B, which is a bounded linear operator in a Banach space X. It is assumed that K acts in the weighted space l α p (Z,X), 1≤p≤∞, of two-sided sequences of vectors from X. The main results are obtained in terms of the spectrum σ(B) of the operator coefficient B and properties of the weight function. Applications to the study of the spectrum of a differential operator with an unbounded operator coefficient (the generator of a strongly continuous semigroup of operators) in weighted function spaces are given. Bibliography: 23 titles

  13. Spectrophotometric intracutaneous analysis for differential diagnosis of pigmented skin lesions

    Directory of Open Access Journals (Sweden)

    Е. V. Filonenko

    2013-01-01

    Full Text Available The non-invasive diagnosis of pigmented skin lesions by spectrophotometric intracutaneous analysis (SIA-scopy using device for dermatoscopy (SIAscope V by Astron Clinica, Ltd was approved in P.A.Herzen Moscow Cancer Research Institute. The method is based on analysis of light interaction with wavelength of 440–960 nm anf human skin, which is recorded by change of image on scan. The comparative analysis of SIA-scopy and histological data in 327 pigmented skin lesions in 147 patients showed, that SIA had high diagnostic efficiency for cutaneous melanoma: the sensitivity was 96%, specifity – 94%, diagnostic accuracy – 94%. For study of malignant potential of pigmented lesions by SIA-scopy the most informative capacity was obtained for assessment of melanin in papillary dermis, status of blood vessels and collagen fibres (SIA-scans 3, 4, 5.

  14. Heterokaryon analysis of muscle differentiation: regulation of the postmitotic state.

    Science.gov (United States)

    Clegg, C H; Hauschka, S D

    1987-08-01

    MM14 mouse myoblasts withdraw irreversibly from the cell cycle and become postmitotic within a few hours of being deprived of fibroblast growth factor (Clegg, C. H., T. A. Linkhart, B. B. Olwin, and S. D. Hauschka, 1987, J. Cell Biol., 105:949-956). To examine the mechanisms that may regulate this developmental state of skeletal muscle, we tested the mitogen responsiveness of various cell types after their polyethylene glycol-mediated fusion with post-mitotic myocytes. Heterokaryons containing myocytes and quiescent nonmyogenic cells such as 3T3, L cell, and a differentiation-defective myoblast line (DD-1) responded to mitogen-rich medium by initiating DNA synthesis. Myonuclei replicated DNA and reexpressed thymidine kinase. In contrast, (myocyte x G1 myoblast) heterokaryons failed to replicate DNA in mitogen-rich medium and became postmitotic. This included cells with a nuclear ratio of three myoblasts to one myocyte. Proliferation dominance in (myocyte x 3T3 cell) and (myocyte x DD-1) heterokaryons was conditionally regulated by the timing of mitogen treatment; such cells became postmitotic when mitogen exposure was delayed for as little as 6 h after cell fusion. In addition, (myocyte x DD-1) heterokaryons expressed a muscle-specific trait and lost epidermal growth factor receptors when they became postmitotic. These results demonstrate that DNA synthesis is not irreversibly blocked in skeletal muscle; myonuclei readily express proliferation-related functions when provided with a mitogenic signal. Rather, myocyte-specific repression of DNA synthesis in heterokaryons argues that the postmitotic state of skeletal muscle is regulated by diffusible factors that inhibit processes of cellular mitogenesis.

  15. Analysis of an Nth-order nonlinear differential-delay equation

    Science.gov (United States)

    Vallée, Réal; Marriott, Christopher

    1989-01-01

    The problem of a nonlinear dynamical system with delay and an overall response time which is distributed among N individual components is analyzed. Such a system can generally be modeled by an Nth-order nonlinear differential delay equation. A linear-stability analysis as well as a numerical simulation of that equation are performed and a comparison is made with the experimental results. Finally, a parallel is established between the first-order differential equation with delay and the Nth-order differential equation without delay.

  16. Multiresolution Analysis by Infinitely Differentiable Compactly Supported Functions

    Science.gov (United States)

    1992-09-01

    Math. Surveys 45:1 (1990), 87-120. [I] (;. Strang and G. Fix, A Fourier analysis of the finite element variational method. C.I.M.F. I 1 Ciclo 1971, in Constructi’c Aspects of Functional Analyszs ed. G. Geymonat 1973, 793-840. 10

  17. Application of spectral analysis for differentiation between metals using signals from eddy-current transducers

    OpenAIRE

    Abramovych, Anton; Poddubny, Volodymyr

    2017-01-01

    The authors theoretically and experimentally substantiated the use of the spectral method for processing a signal of the vortex-current metal detector for dichotomous differentiation between metals. Results of experimental research that prove the possibility of using spectral analysis for differentiation between metals were presented. The vortex-current method for detection of hidden metal objects was analyzed. It was indicated that amplitude of output VCD signal is determined by electric con...

  18. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis...... intermediates, were upregulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 upregulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two nonproducing mutants, restricted to a sub...

  19. An analysis of income differentials by marital status

    Directory of Open Access Journals (Sweden)

    Regina Madalozzo

    2008-01-01

    Full Text Available Unmarried cohabitation has become a more frequently observed phenomenon over the last three decades, and not only in the United States. The objective of this work is to examine income differentials between married women and those who remain single or cohabitate. The empirical literature shows that, while the marriage premium is verified in different studies for men, the result for women is not conclusive. The main innovation of my study is the existence of controls for selection. In this study, we have two sources of selectivity: into the labor force and into a marital status category. The switching regressions and the Oaxaca decomposition results demonstrate the existence of a significant penalty for marriage. Correcting for both types of selection, the difference in wages varies between 49% and 53%, when married women are compared with cohabiting ones, and favors non-married women. This result points to the existence of a marriage penalty.O casamento não oficializado, coabitação, tem se tornado cada vez mais freqüente nas últimas décadas. O objetivo deste trabalho é examinar a relação entre os salários das mulheres casadas e das solteiras ou coabitantes. A literatura a este respeito mostra que, enquanto o prêmio financeiro para o casamento é verificado em diversos estudos e países quando o objeto de estudo são os homens, o resultado para mulheres não é conclusivo. A principal inovação do presente estudo é a existência de controles para seleção, tanto na escolha em participar da força de trabalho como de alterar seu estado civil. Regressões "switching" e decomposição de Oaxaca mostram a existência de uma penalização financeira para mulheres casadas. Corrigindo para ambos os tipos de seleção, a diferença nos salários das mulheres casadas com relação às coabitantes varia entre 49% e 53%, favorecendo as coabitantes. Este resultado aponta para a existência de uma penalidade ao casamento.

  20. Analysis of the F. Calogero Type Projection-Algebraic Scheme for Differential Operator Equations

    International Nuclear Information System (INIS)

    Lustyk, Miroslaw; Bogolubov, Nikolai N. Jr.; Blackmore, Denis; Prykarpatsky, Anatoliy K.

    2010-12-01

    The existence, convergence, realizability and stability of solutions of differential operator equations obtained via a novel projection-algebraic scheme are analyzed in detail. This analysis is based upon classical discrete approximation techniques coupled with a recent generalization of the Leray-Schauder fixed point theorem. An example is included to illustrate the efficacy of the projection scheme and analysis strategy. (author)

  1. Differential operators in a Clifford analysis associated to differential equations with anti-monogenic right-hand sides

    International Nuclear Information System (INIS)

    Nguyen Thanh Van

    2006-12-01

    This paper deals with the initial value problem of the type φw / φt = L (t, x, w, φw / φx i ) (1) w(0, x) = φ(x) (2) where t is the time, L is a linear first order operator in a Clifford Analysis and φ is a generalized monogenic function. We give sufficient conditions on the coefficients of operator L under which L is associated to differential equations with anti-monogenic right-hand sides. For such operator L the initial problem (1),(2) is solvable for an arbitrary generalized monogenic initial function φ and the solution is also generalized monogenic for each t. (author)

  2. Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144 during endothelial differentiation

    Directory of Open Access Journals (Sweden)

    Libermann Towia

    2008-05-01

    Full Text Available Abstract Background Endothelial differentiation occurs during normal vascular development in the developing embryo. This process is recapitulated in the adult when endothelial progenitor cells are generated in the bone marrow and can contribute to vascular repair or angiogenesis at sites of vascular injury or ischemia. The molecular mechanisms of endothelial differentiation remain incompletely understood. Novel approaches are needed to identify the factors that regulate endothelial differentiation. Methods Mouse embryonic stem (ES cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2+ cells, that were CD41 positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin was also identified at this same time point. Channels lined by VE-cadherin positive cells developed within the embryoid bodies (EBs formed by differentiating ES cells. VE-cadherin and CD41 expressing cells differentiate in close proximity to each other within the EBs, supporting the concept of a common origin for cells of hematopoietic and endothelial lineages. Results Microarray analysis of >45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2+, CD41+, and CD144+ and VEGF-R2-, CD41-, and CD144-. All microarray experiments were performed in duplicate using RNA obtained from independent experiments, for each subset of cells. Expression profiling confirmed the role of several genes involved in hematopoiesis, and identified several putative genes involved in endothelial differentiation. Conclusion The isolation of CD144+ cells during ES cell differentiation from embryoid bodies provides an excellent model system and method for identifying genes that are expressed during endothelial differentiation and that

  3. A methodology for the analysis of differential coexpression across the human lifespan.

    Science.gov (United States)

    Gillis, Jesse; Pavlidis, Paul

    2009-09-22

    Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge. Here we introduce a method for analyzing changes in coexpression across multiple ordered groups (e.g., over time) and extensively test its validity and usefulness. Our method is based on the use of the Haar basis set to efficiently represent changes in coexpression at multiple time scales, and thus represents a principled and generalizable extension of the idea of differential coexpression to life stage data. We used published microarray studies categorized by age to test the methodology. We validated the methodology by testing our ability to reconstruct Gene Ontology (GO) categories using our measure of differential coexpression and compared this result to using coexpression alone. Our method allows significant improvement in characterizing these groups of genes. Further, we examine the statistical properties of our measure of differential coexpression and establish that the results are significant both statistically and by an improvement in semantic similarity. In addition, we found that our method finds more significant changes in gene relationships compared to several other methods of expressing temporal relationships between genes, such as coexpression over time. Differential coexpression over age generates significant and biologically relevant information about the genes producing it. Our Haar basis methodology for determining age-related differential coexpression performs better than other tested methods. The Haar basis set also lends itself to ready interpretation

  4. Analysis of differential lipofection efficiency in primary and established myoblasts.

    Science.gov (United States)

    Pampinella, Francesca; Lechardeur, Delphine; Zanetti, Elena; MacLachlan, Ian; Benharouga, Mohammed; Lukacs, Gergely L; Vitiello, Libero

    2002-02-01

    In this study we have compared the process of lipid-mediated transfection in primary and established myoblasts, in an attempt to elucidate the mechanisms responsible for the scarce transfectability of the former. We determined the metabolic stability of cytoplasmically injected and lipofected DNA in primary and established myoblasts and carried out a comparative time course analysis of luciferase reporter-gene expression and DNA stability. The efficiency of the transcription-translation machinery of the two cell types was compared by intranuclear injection of naked plasmid DNA encoding luciferase. Subcellular colocalization of fluorescein-labeled lipopolyplexes with specific endosomal and lysosomal markers was performed by confocal microscopy to monitor the intracellular trafficking of plasmid DNA during transfection. The metabolic stability of plasmid DNA was similar in primary and established myoblasts after both lipofection and cytoplasmic injection. In both cell types, lipofection had no detectable effect on the rate of cell proliferation. Confocal analysis showed that nuclear translocation of transfected DNA coincided with localization in a compartment devoid of endosome- or lysosome-specific marker proteins. The residency time of plasmid DNA in this compartment differed for primary and established myoblasts. Our findings suggest that the lower transfectability of primary myoblasts is mostly due to a difference in the intracellular delivery pathway that correlates with more rapid delivery of internalized complex to the lysosomal compartment.

  5. Automated differentiation of computer models for sensitivity analysis

    International Nuclear Information System (INIS)

    Worley, B.A.

    1990-01-01

    Sensitivity analysis of reactor physics computer models is an established discipline after more than twenty years of active development of generalized perturbations theory based on direct and adjoint methods. Many reactor physics models have been enhanced to solve for sensitivities of model results to model data. The calculated sensitivities are usually normalized first derivatives although some codes are capable of solving for higher-order sensitivities. The purpose of this paper is to report on the development and application of the GRESS system for automating the implementation of the direct and adjoint techniques into existing FORTRAN computer codes. The GRESS system was developed at ORNL to eliminate the costly man-power intensive effort required to implement the direct and adjoint techniques into already-existing FORTRAN codes. GRESS has been successfully tested for a number of codes over a wide range of applications and presently operates on VAX machines under both VMS and UNIX operating systems

  6. Automated differentiation of computer models for sensitivity analysis

    International Nuclear Information System (INIS)

    Worley, B.A.

    1991-01-01

    Sensitivity analysis of reactor physics computer models is an established discipline after more than twenty years of active development of generalized perturbations theory based on direct and adjoint methods. Many reactor physics models have been enhanced to solve for sensitivities of model results to model data. The calculated sensitivities are usually normalized first derivatives, although some codes are capable of solving for higher-order sensitivities. The purpose of this paper is to report on the development and application of the GRESS system for automating the implementation of the direct and adjoint techniques into existing FORTRAN computer codes. The GRESS system was developed at ORNL to eliminate the costly man-power intensive effort required to implement the direct and adjoint techniques into already-existing FORTRAN codes. GRESS has been successfully tested for a number of codes over a wide range of applications and presently operates on VAX machines under both VMS and UNIX operating systems. (author). 9 refs, 1 tab

  7. Differential expression analysis of genic male sterility by cDNA-AFLP in maize

    International Nuclear Information System (INIS)

    Zhang Linbi; Rong Tingzhao; Pan Guangtang; Cao Moju

    2009-01-01

    The differential expression of male sterility induced by space flight with male fertility was studied using cDNA-AFLP technology. Total RNA was isolated from anther of male sterility and male fertility. Nine differential expression cDNA fragments were obtained with 16 primer combinations. The differential cDNA fragments were eluted, cloned and sequenced. Then half-quantitative RT-PCR was used to stuy the differential expressions of 4 development stages between sterility and fertility. Sequencing analysis shown 2 fragments from male sterility might be novel genes. Four fragments from male fertility were homology as chalcone and stilbene synthases, putative acyl CoA dehydrogenase, putative protein kinases and putative glycine decarboxylase. All these proteins might participate in the energy metabolisms, substance metabolisms or signal pollen development, Z8 took on increasing expression during the middle period of pollen development. These results just met the demand of more energy and more substance during the pollen development. (authors)

  8. Differential Power Analysis as a digital forensic tool.

    Science.gov (United States)

    Souvignet, T; Frinken, J

    2013-07-10

    Electronic payment fraud is considered a serious international crime by Europol. An important part of this fraud comes from payment card data skimming. This type of fraud consists of an illegal acquisition of payment card details when a user is withdrawing cash at an automated teller machine (ATM) or paying at a point of sale (POS). Modern skimming devices, also known as skimmers, use secure crypto-algorithms (e.g. Advanced Encryption Standard (AES)) to protect skimmed data stored within their memory. In order to provide digital evidence in criminal cases involving skimmers, law enforcement agencies (LEAs) must retrieve the plaintext skimmed data, generally without having knowledge of the secret key. This article proposes an alternative to the current solution at the Bundeskriminalamt (BKA) to reveal the secret key. The proposed solution is non-invasive, based on Power Analysis Attack (PAA). This article first describes the structure and the behaviour of an AES skimmer, followed by the proposal of the full operational PAA process, from power measurements to attack computation. Finally, it presents results obtained in several cases, explaining the latest improvements and providing some ideas for further developments. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

    International Nuclear Information System (INIS)

    Pinheiro, Céline; Garcia, Eduardo A.; Morais-Santos, Filipa; Moreira, Marise A. R.; Almeida, Fábio M.; Jubé, Luiz F.; Queiroz, Geraldo S.; Paula, Élbio C.; Andreoli, Maria A.; Villa, Luisa L.; Longatto-Filho, Adhemar; Baltazar, Fátima

    2015-01-01

    Deregulation of cellular energetic metabolism was recently pointed out as a hallmark of cancer cells. This deregulation involves a metabolic reprogramming that leads to a high production of lactate. Lactate efflux, besides contributing for the glycolytic flux, also acts in the extracellular matrix, contributing for cancer malignancy, by, among other effects, induction of angiogenesis. However, studies on the interplay between cancer metabolism and angiogenesis are scarce. Therefore, the aim of the present study was to evaluate the metabolic and vascular molecular profiles of cervical adenocarcinomas, their co-expression, and their relation to the clinical and pathological behavior. The immunohistochemical expression of metabolism-related proteins (MCT1, MCT4, CD147, GLUT1 and CAIX) as well as VEGF family members (VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3) was assessed in a series of 232 cervical adenocarcinomas. The co-expression among proteins was assessed and the expression profiles were associated with patients’ clinicopathological parameters. Among the metabolism-related proteins, MCT4 and CAIX were the most frequently expressed in cervical adenocarcinomas while CD147 was the less frequently expressed protein. Overall, VEGF family members showed a strong and extended expression with VEGF-C and VEGFR-2 as the most frequently expressed and VEGFR-1 as the less expressed member. Co-expression of MCT isoforms with VEGF family members was demonstrated. Finally, MCT4 was associated with parametrial invasion and HPV18 infection, CD147 and GLUT1 with distant metastasis, CAIX with tumor size and HPV18 infection, and VEGFR-1 with local and lymphnode metastasis. The results herein presented provide additional evidence for a crosstalk between deregulating cellular energetics and inducing angiogenesis. Also, the metabolic remodeling and angiogenic switch are relevant to cancer progression and aggressiveness in adenocarcinomas

  10. Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.

    Science.gov (United States)

    Noyan, Kajsa; Nguyen, Son; Betts, Michael R; Sönnerborg, Anders; Buggert, Marcus

    2018-01-01

    Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART. We found that the co-expression pattern of inhibitory receptors was significantly reduced in ELCs compared with HIV-1 cART-treated and viremic subjects, and similar to healthy controls. Markers associated with T cell exhaustion varied among different memory CD4+ T cell subsets and highest levels were found mainly on transitional memory T cells. CD4+ T cells co-expressing all inhibitory markers were positively correlated to T cell activation (CD38+ HLA-DR+) as well as the transcription factors Helios and FoxP3. Finally, clinical parameters such as CD4 count, HIV-1 viral load, and the CD4/CD8 ratio all showed significant associations with CD4+ T cell exhaustion. We demonstrate that ELCs are able to maintain lower levels of CD4+ T cell exhaustion despite years of ongoing viral replication compared with successfully cART-treated subjects. Our findings suggest that ELCs harbor a "healthy" state of inhibitory receptor expression on CD4+ T cells that might play part in maintenance of their control status.

  11. Automatic differentiation for design sensitivity analysis of structural systems using multiple processors

    Science.gov (United States)

    Nguyen, Duc T.; Storaasli, Olaf O.; Qin, Jiangning; Qamar, Ramzi

    1994-01-01

    An automatic differentiation tool (ADIFOR) is incorporated into a finite element based structural analysis program for shape and non-shape design sensitivity analysis of structural systems. The entire analysis and sensitivity procedures are parallelized and vectorized for high performance computation. Small scale examples to verify the accuracy of the proposed program and a medium scale example to demonstrate the parallel vector performance on multiple CRAY C90 processors are included.

  12. First- and Second-Order Full-Differential in Edge Analysis of Images

    Directory of Open Access Journals (Sweden)

    Dong-Mei Pu

    2014-01-01

    mathematics. We propose and reformulate them with a uniform definition framework. Based on our observation and analysis with the difference, we propose an algorithm to detect the edge from image. Experiments on Corel5K and PASCAL VOC 2007 are done to show the difference between the first order and the second order. After comparison with Canny operator and the proposed first-order differential, the main result is that the second-order differential has the better performance in analysis of changes of the context of images with good selection of control parameter.

  13. Improved production of biohydrogen in light-powered Escherichia coli by co-expression of proteorhodopsin and heterologous hydrogenase

    Directory of Open Access Journals (Sweden)

    Kim Jaoon YH

    2012-01-01

    Full Text Available Abstract Background Solar energy is the ultimate energy source on the Earth. The conversion of solar energy into fuels and energy sources can be an ideal solution to address energy problems. The recent discovery of proteorhodopsin in uncultured marine γ-proteobacteria has made it possible to construct recombinant Escherichia coli with the function of light-driven proton pumps. Protons that translocate across membranes by proteorhodopsin generate a proton motive force for ATP synthesis by ATPase. Excess protons can also be substrates for hydrogen (H2 production by hydrogenase in the periplasmic space. In the present work, we investigated the effect of the co-expression of proteorhodopsin and hydrogenase on H2 production yield under light conditions. Results Recombinant E. coli BL21(DE3 co-expressing proteorhodopsin and [NiFe]-hydrogenase from Hydrogenovibrio marinus produced ~1.3-fold more H2 in the presence of exogenous retinal than in the absence of retinal under light conditions (70 μmole photon/(m2·s. We also observed the synergistic effect of proteorhodopsin with endogenous retinal on H2 production (~1.3-fold more with a dual plasmid system compared to the strain with a single plasmid for the sole expression of hydrogenase. The increase of light intensity from 70 to 130 μmole photon/(m2·s led to an increase (~1.8-fold in H2 production from 287.3 to 525.7 mL H2/L-culture in the culture of recombinant E. coli co-expressing hydrogenase and proteorhodopsin in conjunction with endogenous retinal. The conversion efficiency of light energy to H2 achieved in this study was ~3.4%. Conclusion Here, we report for the first time the potential application of proteorhodopsin for the production of biohydrogen, a promising alternative fuel. We showed that H2 production was enhanced by the co-expression of proteorhodopsin and [NiFe]-hydrogenase in recombinant E. coli BL21(DE3 in a light intensity-dependent manner. These results demonstrate that E. coli

  14. Small-Signal Modeling and Analysis of Grid-Connected Inverter with Power Differential Droop Control

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2016-01-01

    Full Text Available The conventional voltage and frequency droop control strategy in grid-connected inverter suffers a major setback in the presence of disturbance by producing oscillations. Adding a power differential term in droop controller is an effective way to address such drawback. In this paper, grid-connected inverter’s small-signal models of the conventional droop control and the power differential droop control are established. The eigenvalues of the models are then determined by system matrix. The eigenvalues analysis is presented which helps in identifying the relationship between the system stability and controller parameters. It is concluded that the damping ratio of dominant low-frequency eigenvalues increased and the oscillation caused by the disturbance is suppressed when a power differential term is added to the droop control method. The MATLAB/Simulink models of grid-connected inverter with both control strategies are also established to validate the results of small-signal analysis.

  15. Global transcriptome analysis of spore formation in Myxococcus xanthus reveals a locus necessary for cell differentiation

    Directory of Open Access Journals (Sweden)

    Treuner-Lange Anke

    2010-04-01

    Full Text Available Abstract Background Myxococcus xanthus is a Gram negative bacterium that can differentiate into metabolically quiescent, environmentally resistant spores. Little is known about the mechanisms involved in differentiation in part because sporulation is normally initiated at the culmination of a complex starvation-induced developmental program and only inside multicellular fruiting bodies. To obtain a broad overview of the sporulation process and to identify novel genes necessary for differentiation, we instead performed global transcriptome analysis of an artificial chemically-induced sporulation process in which addition of glycerol to vegetatively growing liquid cultures of M. xanthus leads to rapid and synchronized differentiation of nearly all cells into myxospore-like entities. Results Our analyses identified 1 486 genes whose expression was significantly regulated at least two-fold within four hours of chemical-induced differentiation. Most of the previously identified sporulation marker genes were significantly upregulated. In contrast, most genes that are required to build starvation-induced multicellular fruiting bodies, but which are not required for sporulation per se, were not significantly regulated in our analysis. Analysis of functional gene categories significantly over-represented in the regulated genes, suggested large rearrangements in core metabolic pathways, and in genes involved in protein synthesis and fate. We used the microarray data to identify a novel operon of eight genes that, when mutated, rendered cells unable to produce viable chemical- or starvation-induced spores. Importantly, these mutants displayed no defects in building fruiting bodies, suggesting these genes are necessary for the core sporulation process. Furthermore, during the starvation-induced developmental program, these genes were expressed in fruiting bodies but not in peripheral rods, a subpopulation of developing cells which do not sporulate

  16. Fractional Order Differentiation by Integration and Error Analysis in Noisy Environment

    KAUST Repository

    Liu, Dayan

    2015-03-31

    The integer order differentiation by integration method based on the Jacobi orthogonal polynomials for noisy signals was originally introduced by Mboup, Join and Fliess. We propose to extend this method from the integer order to the fractional order to estimate the fractional order derivatives of noisy signals. Firstly, two fractional order differentiators are deduced from the Jacobi orthogonal polynomial filter, using the Riemann-Liouville and the Caputo fractional order derivative definitions respectively. Exact and simple formulae for these differentiators are given by integral expressions. Hence, they can be used for both continuous-time and discrete-time models in on-line or off-line applications. Secondly, some error bounds are provided for the corresponding estimation errors. These bounds allow to study the design parameters\\' influence. The noise error contribution due to a large class of stochastic processes is studied in discrete case. The latter shows that the differentiator based on the Caputo fractional order derivative can cope with a class of noises, whose mean value and variance functions are polynomial time-varying. Thanks to the design parameters analysis, the proposed fractional order differentiators are significantly improved by admitting a time-delay. Thirdly, in order to reduce the calculation time for on-line applications, a recursive algorithm is proposed. Finally, the proposed differentiator based on the Riemann-Liouville fractional order derivative is used to estimate the state of a fractional order system and numerical simulations illustrate the accuracy and the robustness with respect to corrupting noises.

  17. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    Energy Technology Data Exchange (ETDEWEB)

    Kalra, Rajkumar S., E-mail: renu-wadhwa@aist.go.jp; Wadhwa, Renu, E-mail: renu-wadhwa@aist.go.jp [Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science and Technology (AIST Central 4), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan)

    2015-02-27

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.

  18. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    International Nuclear Information System (INIS)

    Kalra, Rajkumar S.; Wadhwa, Renu

    2015-01-01

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein

  19. MCT1 modulates cancer cell pyruvate export and growth of tumors that co-express MCT1 and MCT4

    Science.gov (United States)

    Hong, Candice Sun; Graham, Nicholas A.; Gu, Wen; Camacho, Carolina Espindola; Mah, Vei; Maresh, Erin L.; Alavi, Mohammed; Bagryanova, Lora; Krotee, Pascal A. L.; Gardner, Brian K.; Behbahan, Iman Saramipoor; Horvath, Steve; Chia, David; Mellinghoff, Ingo K.; Hurvitz, Sara A.; Dubinett, Steven M.; Critchlow, Susan E.; Kurdistani, Siavash K.; Goodglick, Lee; Braas, Daniel; Graeber, Thomas G.; Christofk, Heather R.

    2016-01-01

    SUMMARY Monocarboxylate Transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors further supporting their use as anti-cancer therapeutics. PMID:26876179

  20. Step-by-Step Construction of Gene Co-expression Networks from High-Throughput Arabidopsis RNA Sequencing Data.

    Science.gov (United States)

    Contreras-López, Orlando; Moyano, Tomás C; Soto, Daniela C; Gutiérrez, Rodrigo A

    2018-01-01

    The rapid increase in the availability of transcriptomics data generated by RNA sequencing represents both a challenge and an opportunity for biologists without bioinformatics training. The challenge is handling, integrating, and interpreting these data sets. The opportunity is to use this information to generate testable hypothesis to understand molecular mechanisms controlling gene expression and biological processes (Fig. 1). A successful strategy to generate tractable hypotheses from transcriptomics data has been to build undirected network graphs based on patterns of gene co-expression. Many examples of new hypothesis derived from network analyses can be found in the literature, spanning different organisms including plants and specific fields such as root developmental biology.In order to make the process of constructing a gene co-expression network more accessible to biologists, here we provide step-by-step instructions using published RNA-seq experimental data obtained from a public database. Similar strategies have been used in previous studies to advance root developmental biology. This guide includes basic instructions for the operation of widely used open source platforms such as Bio-Linux, R, and Cytoscape. Even though the data we used in this example was obtained from Arabidopsis thaliana, the workflow developed in this guide can be easily adapted to work with RNA-seq data from any organism.

  1. Differential Item Functioning Analysis of the Mental, Emotional, and Bodily Toughness Inventory

    Science.gov (United States)

    Gao, Yong; Mack, Mick G.; Ragan, Moira A.; Ragan, Brian

    2012-01-01

    In this study the authors used differential item functioning analysis to examine if there were items in the Mental, Emotional, and Bodily Toughness Inventory functioning differently across gender and athletic membership. A total of 444 male (56.3%) and female (43.7%) participants (30.9% athletes and 69.1% non-athletes) responded to the Mental,…

  2. Cytogenetic analysis of a case of myxoid liposarcoma with cartilaginous differentiation

    NARCIS (Netherlands)

    Dijkhuizen, T; Molenaar, WM; Hoekstra, HJ; Wiersema, J; vandenBerg, E

    1996-01-01

    The cytogenetic analysis of a patient with a myxoid liposarcoma exhibiting cartilaginous differentiation is presented. A complex translocation involving chromosome 12, 16, and 19 was found, instead of the t(12;16), specific for myxoid liposarcoma. The involvement of 19q13 in a tumor with

  3. Functional analytic methods in complex analysis and applications to partial differential equations

    International Nuclear Information System (INIS)

    Mshimba, A.S.A.; Tutschke, W.

    1990-01-01

    The volume contains 24 lectures given at the Workshop on Functional Analytic Methods in Complex Analysis and Applications to Partial Differential Equations held in Trieste, Italy, between 8-19 February 1988, at the ICTP. A separate abstract was prepared for each of these lectures. Refs and figs

  4. Analysis of a first-order delay differential-delay equation containing two delays

    Science.gov (United States)

    Marriott, C.; Vallée, R.; Delisle, C.

    1989-09-01

    An experimental and numerical analysis of the behavior of a two-delay differential equation is presented. It is shown that much of the system's behavior can be related to the stability behavior of the underlying linearized modes. A new phenomenon, mode crossing, is explored.

  5. Use of differential item functioning analysis to assess the equivalence of translations of a questionnaire

    NARCIS (Netherlands)

    Petersen, Morten Aa; Groenvold, Mogens; Bjorner, Jakob B.; Aaronson, Neil; Conroy, Thierry; Cull, Ann; Fayers, Peter; Hjermstad, Marianne; Sprangers, Mirjam; Sullivan, Marianne

    2003-01-01

    In cross-national comparisons based on questionnaires, accurate translations are necessary to obtain valid results. Differential item functioning (DIF) analysis can be used to test whether translations of items in multi-item scales are equivalent to the original. In data from 10,815 respondents

  6. Factor analysis of the scale of prodromal symptoms: differentiating between negative and depression symptoms

    NARCIS (Netherlands)

    Klaassen, Rianne M. C.; Velthorst, Eva; Nieman, Dorien H.; de Haan, Lieuwe; Becker, Hiske E.; Dingemans, Peter M.; van de Fliert, J. Reinaud; van der Gaag, Mark; Linszen, Don H.

    2011-01-01

    This study examines the ability of the Scale of Prodromal Symptoms (SOPS) to differentiate between negative and depression symptoms in a young help-seeking ultrahigh risk (UHR) group. SOPS data of 77 help-seeking patients at UHR for psychosis were analyzed with an exploratory factor analysis. The

  7. Stepwise Analysis of Differential Item Functioning Based on Multiple-Group Partial Credit Model.

    Science.gov (United States)

    Muraki, Eiji

    1999-01-01

    Extended an Item Response Theory (IRT) method for detection of differential item functioning to the partial credit model and applied the method to simulated data using a stepwise procedure. Then applied the stepwise DIF analysis based on the multiple-group partial credit model to writing trend data from the National Assessment of Educational…

  8. On the analysis of a complex differential game using artificial intelligence techniques [military systems

    NARCIS (Netherlands)

    Shinar, J.; Siegel, A.W.

    1988-01-01

    The investigation is motivated by the dynamic conflict in an air-to-air combat between two aggressive aircraft, both equipped with medium-range guided missiles. It is a two-target differential game with two independent pursuit-evasion games. A description is given of the analysis of the conflict by

  9. Social Concepts and Judgments: A Semantic Differential Analysis of the Concepts Feminist, Man, and Woman

    Science.gov (United States)

    Pierce, W. David; Sydie, R. A.; Stratkotter, Rainer

    2003-01-01

    Male and female participants (N = 274) made judgments about the social concepts of "feminist," "man," and "woman" on 63 semantic differential items. Factor analysis identified three basic dimensions termed evaluative, potency, and activity as well as two secondary factors called expressiveness and sexuality. Results for the evaluative dimension…

  10. Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal

    OpenAIRE

    Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

    2015-01-01

    A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transf...

  11. Differential die-away analysis system response modeling and detector design

    International Nuclear Information System (INIS)

    Jordan, K.A.; Gozani, T.; Vujic, J.

    2008-01-01

    Differential die-away-analysis (DDAA) is a sensitive technique to detect presence of fissile materials such as 235 U and 239 Pu. DDAA uses a high-energy (14 MeV) pulsed neutron generator to interrogate a shipping container. The signature is a fast neutron signal hundreds of microseconds after the cessation of the neutron pulse. This fast neutron signal has decay time identical to the thermal neutron diffusion decay time of the inspected cargo. The theoretical aspects of a cargo inspection system based on the differential die-away technique are explored. A detailed mathematical model of the system is developed, and experimental results validating this model are presented

  12. Gas stream analysis using voltage-current time differential operation of electrochemical sensors

    Science.gov (United States)

    Woo, Leta Yar-Li; Glass, Robert Scott; Fitzpatrick, Joseph Jay; Wang, Gangqiang; Henderson, Brett Tamatea; Lourdhusamy, Anthoniraj; Steppan, James John; Allmendinger, Klaus Karl

    2018-01-02

    A method for analysis of a gas stream. The method includes identifying an affected region of an affected waveform signal corresponding to at least one characteristic of the gas stream. The method also includes calculating a voltage-current time differential between the affected region of the affected waveform signal and a corresponding region of an original waveform signal. The affected region and the corresponding region of the waveform signals have a sensitivity specific to the at least one characteristic of the gas stream. The method also includes generating a value for the at least one characteristic of the gas stream based on the calculated voltage-current time differential.

  13. Analysis of the differential-phase-shift-keying protocol in the quantum-key-distribution system

    International Nuclear Information System (INIS)

    Rong-Zhen, Jiao; Chen-Xu, Feng; Hai-Qiang, Ma

    2009-01-01

    The analysis is based on the error rate and the secure communication rate as functions of distance for three quantum-key-distribution (QKD) protocols: the Bennett–Brassard 1984, the Bennett–Brassard–Mermin 1992, and the coherent differential-phase-shift keying (DPSK) protocols. We consider the secure communication rate of the DPSK protocol against an arbitrary individual attack, including the most commonly considered intercept-resend and photon-number splitting attacks, and concluded that the simple and efficient differential-phase-shift-keying protocol allows for more than 200 km of secure communication distance with high communication rates. (general)

  14. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions : A pooled analysis

    NARCIS (Netherlands)

    van der Waaij, LA; van Dullemen, HM; Porte, RJ

    Background: Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the

  15. Incorporating prior information into differential network analysis using non-paranormal graphical models.

    Science.gov (United States)

    Zhang, Xiao-Fei; Ou-Yang, Le; Yan, Hong

    2017-08-15

    Understanding how gene regulatory networks change under different cellular states is important for revealing insights into network dynamics. Gaussian graphical models, which assume that the data follow a joint normal distribution, have been used recently to infer differential networks. However, the distributions of the omics data are non-normal in general. Furthermore, although much biological knowledge (or prior information) has been accumulated, most existing methods ignore the valuable prior information. Therefore, new statistical methods are needed to relax the normality assumption and make full use of prior information. We propose a new differential network analysis method to address the above challenges. Instead of using Gaussian graphical models, we employ a non-paranormal graphical model that can relax the normality assumption. We develop a principled model to take into account the following prior information: (i) a differential edge less likely exists between two genes that do not participate together in the same pathway; (ii) changes in the networks are driven by certain regulator genes that are perturbed across different cellular states and (iii) the differential networks estimated from multi-view gene expression data likely share common structures. Simulation studies demonstrate that our method outperforms other graphical model-based algorithms. We apply our method to identify the differential networks between platinum-sensitive and platinum-resistant ovarian tumors, and the differential networks between the proneural and mesenchymal subtypes of glioblastoma. Hub nodes in the estimated differential networks rediscover known cancer-related regulator genes and contain interesting predictions. The source code is at https://github.com/Zhangxf-ccnu/pDNA. szuouyl@gmail.com. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  16. Subtype differentiation of renal tumors using voxel-based histogram analysis of intravoxel incoherent motion parameters.

    Science.gov (United States)

    Gaing, Byron; Sigmund, Eric E; Huang, William C; Babb, James S; Parikh, Nainesh S; Stoffel, David; Chandarana, Hersh

    2015-03-01

    The aim of this study was to determine if voxel-based histogram analysis of intravoxel incoherent motion imaging (IVIM) parameters can differentiate various subtypes of renal tumors, including benign and malignant lesions. A total of 44 patients with renal tumors who underwent surgery and had histopathology available were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, single-institution prospective study. In addition to routine renal magnetic resonance imaging examination performed on a 1.5-T system, all patients were imaged with axial diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal data using a segmented algorithm to extract the IVIM parameters perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each voxel. Mean and histogram measures of heterogeneity (standard deviation, skewness, and kurtosis) of IVIM parameters were correlated with pathology results of tumor subtype using unequal variance t tests to compare subtypes in terms of each measure. Correction for multiple comparisons was accomplished using the Tukey honestly significant difference procedure. A total of 44 renal tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5 cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and 3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC) was differentiated by mean analysis but not by histogram analysis. However, 2 other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by histogram distribution parameters exclusively. The standard deviation of Dt [σ(Dt)] differentiated ccRCC (0.362 ± 0.136 × 10 mm/s) from AML (0.199 ± 0.043 × 10 mm/s) (P = 0

  17. Comparative transcriptome analysis reveals differentially expressed genes associated with sex expression in garden asparagus (Asparagus officinalis).

    Science.gov (United States)

    Li, Shu-Fen; Zhang, Guo-Jun; Zhang, Xue-Jin; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

    2017-08-22

    Garden asparagus (Asparagus officinalis) is a highly valuable vegetable crop of commercial and nutritional interest. It is also commonly used to investigate the mechanisms of sex determination and differentiation in plants. However, the sex expression mechanisms in asparagus remain poorly understood. De novo transcriptome sequencing via Illumina paired-end sequencing revealed more than 26 billion bases of high-quality sequence data from male and female asparagus flower buds. A total of 72,626 unigenes with an average length of 979 bp were assembled. In comparative transcriptome analysis, 4876 differentially expressed genes (DEGs) were identified in the possible sex-determining stage of female and male/supermale flower buds. Of these DEGs, 433, including 285 male/supermale-biased and 149 female-biased genes, were annotated as flower related. Of the male/supermale-biased flower-related genes, 102 were probably involved in anther development. In addition, 43 DEGs implicated in hormone response and biosynthesis putatively associated with sex expression and reproduction were discovered. Moreover, 128 transcription factor (TF)-related genes belonging to various families were found to be differentially expressed, and this finding implied the essential roles of TF in sex determination or differentiation in asparagus. Correlation analysis indicated that miRNA-DEG pairs were also implicated in asparagus sexual development. Our study identified a large number of DEGs involved in the sex expression and reproduction of asparagus, including known genes participating in plant reproduction, plant hormone signaling, TF encoding, and genes with unclear functions. We also found that miRNAs might be involved in the sex differentiation process. Our study could provide a valuable basis for further investigations on the regulatory networks of sex determination and differentiation in asparagus and facilitate further genetic and genomic studies on this dioecious species.

  18. Evaluation of PCR and high-resolution melt curve analysis for differentiation of Salmonella isolates.

    Science.gov (United States)

    Saeidabadi, Mohammad Sadegh; Nili, Hassan; Dadras, Habibollah; Sharifiyazdi, Hassan; Connolly, Joanne; Valcanis, Mary; Raidal, Shane; Ghorashi, Seyed Ali

    2017-06-01

    Consumption of poultry products contaminated with Salmonella is one of the major causes of foodborne diseases worldwide and therefore detection and differentiation of Salmonella spp. in poultry is important. In this study, oligonucleotide primers were designed from hemD gene and a PCR followed by high-resolution melt (HRM) curve analysis was developed for rapid differentiation of Salmonella isolates. Amplicons of 228 bp were generated from 16 different Salmonella reference strains and from 65 clinical field isolates mainly from poultry farms. HRM curve analysis of the amplicons differentiated Salmonella isolates and analysis of the nucleotide sequence of the amplicons from selected isolates revealed that each melting curve profile was related to a unique DNA sequence. The relationship between reference strains and tested specimens was also evaluated using a mathematical model without visual interpretation of HRM curves. In addition, the potential of the PCR-HRM curve analysis was evaluated for genotyping of additional Salmonella isolates from different avian species. The findings indicate that PCR followed by HRM curve analysis provides a rapid and robust technique for genotyping of Salmonella isolates to determine the serovar/serotype.

  19. Perturbation-expression analysis identifies RUNX1 as a regulator of human mammary stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Ethan S Sokol

    2015-04-01

    Full Text Available The search for genes that regulate stem cell self-renewal and differentiation has been hindered by a paucity of markers that uniquely label stem cells and early progenitors. To circumvent this difficulty we have developed a method that identifies cell-state regulators without requiring any markers of differentiation, termed Perturbation-Expression Analysis of Cell States (PEACS. We have applied this marker-free approach to screen for transcription factors that regulate mammary stem cell differentiation in a 3D model of tissue morphogenesis and identified RUNX1 as a stem cell regulator. Inhibition of RUNX1 expanded bipotent stem cells and blocked their differentiation into ductal and lobular tissue rudiments. Reactivation of RUNX1 allowed exit from the bipotent state and subsequent differentiation and mammary morphogenesis. Collectively, our findings show that RUNX1 is required for mammary stem cells to exit a bipotent state, and provide a new method for discovering cell-state regulators when markers are not available.

  20. Global Analysis of Differentially Expressed Genes and Proteins in the Wheat Callus Infected by Agrobacterium tumefaciens

    Science.gov (United States)

    Zhou, Xiaohong; Wang, Ke; Lv, Dongwen; Wu, Chengjun; Li, Jiarui; Zhao, Pei; Lin, Zhishan; Du, Lipu; Yan, Yueming; Ye, Xingguo

    2013-01-01

    Agrobacterium-mediated plant transformation is an extremely complex and evolved process involving genetic determinants of both the bacteria and the host plant cells. However, the mechanism of the determinants remains obscure, especially in some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated transformation. In this study, differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were analyzed in wheat callus cells co-cultured with Agrobacterium by using RNA sequencing (RNA-seq) and two-dimensional electrophoresis (2-DE) in conjunction with mass spectrometry (MS). A set of 4,889 DEGs and 90 DEPs were identified, respectively. Most of them are related to metabolism, chromatin assembly or disassembly and immune defense. After comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics datasets simultaneously. In addition, real-time RT-PCR experiments were performed to check the differential expression of the 24 genes, and the results were consistent with the RNA-seq data. According to gene ontology (GO) analysis, we found that a big part of these differentially expressed genes were related to the process of stress or immunity response. Several putative determinants and candidate effectors responsive to Agrobacterium mediated transformation of wheat cells were discussed. We speculate that some of these genes are possibly related to Agrobacterium infection. Our results will help to understand the interaction between Agrobacterium and host cells, and may facilitate developing efficient transformation strategies in cereal crops. PMID:24278131

  1. Global analysis of differentially expressed genes and proteins in the wheat callus infected by Agrobacterium tumefaciens.

    Directory of Open Access Journals (Sweden)

    Xiaohong Zhou

    Full Text Available Agrobacterium-mediated plant transformation is an extremely complex and evolved process involving genetic determinants of both the bacteria and the host plant cells. However, the mechanism of the determinants remains obscure, especially in some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated transformation. In this study, differentially expressed genes (DEGs and differentially expressed proteins (DEPs were analyzed in wheat callus cells co-cultured with Agrobacterium by using RNA sequencing (RNA-seq and two-dimensional electrophoresis (2-DE in conjunction with mass spectrometry (MS. A set of 4,889 DEGs and 90 DEPs were identified, respectively. Most of them are related to metabolism, chromatin assembly or disassembly and immune defense. After comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics datasets simultaneously. In addition, real-time RT-PCR experiments were performed to check the differential expression of the 24 genes, and the results were consistent with the RNA-seq data. According to gene ontology (GO analysis, we found that a big part of these differentially expressed genes were related to the process of stress or immunity response. Several putative determinants and candidate effectors responsive to Agrobacterium mediated transformation of wheat cells were discussed. We speculate that some of these genes are possibly related to Agrobacterium infection. Our results will help to understand the interaction between Agrobacterium and host cells, and may facilitate developing efficient transformation strategies in cereal crops.

  2. Numerical Solution of Nonlinear Fredholm Integro-Differential Equations Using Spectral Homotopy Analysis Method

    Directory of Open Access Journals (Sweden)

    Z. Pashazadeh Atabakan

    2013-01-01

    Full Text Available Spectral homotopy analysis method (SHAM as a modification of homotopy analysis method (HAM is applied to obtain solution of high-order nonlinear Fredholm integro-differential problems. The existence and uniqueness of the solution and convergence of the proposed method are proved. Some examples are given to approve the efficiency and the accuracy of the proposed method. The SHAM results show that the proposed approach is quite reasonable when compared to homotopy analysis method, Lagrange interpolation solutions, and exact solutions.

  3. Mathematical Methods for Engineers and Scientists 2 Vector Analysis, Ordinary Differential Equations and Laplace Transforms

    CERN Document Server

    Tang, Kwong-Tin

    2007-01-01

    Pedagogical insights gained through 30 years of teaching applied mathematics led the author to write this set of student-oriented books. Topics such as complex analysis, matrix theory, vector and tensor analysis, Fourier analysis, integral transforms, ordinary and partial differential equations are presented in a discursive style that is readable and easy to follow. Numerous clearly stated, completely worked out examples together with carefully selected problem sets with answers are used to enhance students' understanding and manipulative skill. The goal is to make students comfortable and confident in using advanced mathematical tools in junior, senior, and beginning graduate courses.

  4. Mathematical Methods for Engineers and Scientists 3 Fourier Analysis, Partial Differential Equations and Variational Methods

    CERN Document Server

    Tang, Kwong-Tin

    2007-01-01

    Pedagogical insights gained through 30 years of teaching applied mathematics led the author to write this set of student oriented books. Topics such as complex analysis, matrix theory, vector and tensor analysis, Fourier analysis, integral transforms, ordinary and partial differential equations are presented in a discursive style that is readable and easy to follow. Numerous clearly stated, completely worked out examples together with carefully selected problem sets with answers are used to enhance students' understanding and manipulative skill. The goal is to make students comfortable and confident in using advanced mathematical tools in junior, senior, and beginning graduate courses.

  5. Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer

    International Nuclear Information System (INIS)

    Peng, Rui-Qing; Zeng, Yi-Xin; Zhang, Xiao-Shi; Wu, Xiao-Jun; Ding, Ya; Li, Chun-Yan; Yu, Xing-Juan; Zhang, Xing; Pan, Zhi-Zhong; Wan, De-Sen; Zheng, Li-Ming

    2010-01-01

    The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer. Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed. The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates. This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response

  6. A Network Approach of Gene Co-expression in the Zea mays/Aspergillus flavus Pathosystem to Map Host/Pathogen Interaction Pathways

    Science.gov (United States)

    Musungu, Bryan M.; Bhatnagar, Deepak; Brown, Robert L.; Payne, Gary A.; OBrian, Greg; Fakhoury, Ahmad M.; Geisler, Matt

    2016-01-01

    A gene co-expression network (GEN) was generated using a dual RNA-seq study with the fungal pathogen Aspergillus flavus and its plant host Zea mays during the initial 3 days of infection. The analysis deciphered novel pathways and mapped genes of interest in both organisms during the infection. This network revealed a high degree of connectivity in many of the previously recognized pathways in Z. mays such as jasmonic acid, ethylene, and reactive oxygen species (ROS). For the pathogen A. flavus, a link between aflatoxin production and vesicular transport was identified within the network. There was significant interspecies correlation of expression between Z. mays and A. flavus for a subset of 104 Z. mays, and 1942 A. flavus genes. This resulted in an interspecies subnetwork enriched in multiple Z. mays genes involved in the production of ROS. In addition to the ROS from Z. mays, there was enrichment in the vesicular transport pathways and the aflatoxin pathway for A. flavus. Included in these genes, a key aflatoxin cluster regulator, AflS, was found to be co-regulated with multiple Z. mays ROS producing genes within the network, suggesting AflS may be monitoring host ROS levels. The entire GEN for both host and pathogen, and the subset of interspecies correlations, is presented as a tool for hypothesis generation and discovery for events in the early stages of fungal infection of Z. mays by A. flavus. PMID:27917194

  7. The arabidopsis wall associated kinase-like 10 gene encodes a functional guanylyl cyclase and is co-expressed with pathogen defense related genes

    KAUST Repository

    Meier, Stuart; Ruzvidzo, Oziniel; Morse, Monique; Donaldson, Lara; Kwezi, Lusisizwe; Gehring, Christoph A

    2010-01-01

    Background: Second messengers have a key role in linking environmental stimuli to physiological responses. One such messenger, guanosine 3?,5?-cyclic monophosphate (cGMP), has long been known to be an essential signaling molecule in many different physiological processes in higher plants, including biotic stress responses. To date, however, the guanylyl cyclase (GC) enzymes that catalyze the formation of cGMP from GTP have largely remained elusive in higher plants. Principal Findings: We have identified an Arabidopsis receptor type wall associated kinase-like molecule (AtWAKL10) as a candidate GC and provide experimental evidence to show that the intracellular domain of AtWAKL10431-700 can generate cGMP in vitro. Further, we also demonstrate that the molecule has kinase activity indicating that AtWAKL10 is a twin-domain catalytic protein. A co-expression and stimulus-specific expression analysis revealed that AtWAKL10 is consistently coexpressed with well characterized pathogen defense related genes and along with these genes is induced early and sharply in response to a range of pathogens and their elicitors. Conclusions: We demonstrate that AtWAKL10 is a twin-domain, kinase-GC signaling molecule that may function in biotic stress responses that are critically dependent on the second messenger cGMP. © 2010 Meier et al.

  8. A Network Approach of Gene Co-expression in the Zea mays/Aspergillus flavus Pathosystem to Map Host/Pathogen Interaction Pathways.

    Science.gov (United States)

    Musungu, Bryan M; Bhatnagar, Deepak; Brown, Robert L; Payne, Gary A; OBrian, Greg; Fakhoury, Ahmad M; Geisler, Matt

    2016-01-01

    A gene co-expression network (GEN) was generated using a dual RNA-seq study with the fungal pathogen Aspergillus flavus and its plant host Zea mays during the initial 3 days of infection. The analysis deciphered novel pathways and mapped genes of interest in both organisms during the infection. This network revealed a high degree of connectivity in many of the previously recognized pathways in Z. mays such as jasmonic acid, ethylene, and reactive oxygen species (ROS). For the pathogen A. flavus , a link between aflatoxin production and vesicular transport was identified within the network. There was significant interspecies correlation of expression between Z. mays and A. flavus for a subset of 104 Z. mays , and 1942 A. flavus genes. This resulted in an interspecies subnetwork enriched in multiple Z. mays genes involved in the production of ROS. In addition to the ROS from Z. mays , there was enrichment in the vesicular transport pathways and the aflatoxin pathway for A. flavus . Included in these genes, a key aflatoxin cluster regulator, AflS, was found to be co-regulated with multiple Z. mays ROS producing genes within the network, suggesting AflS may be monitoring host ROS levels. The entire GEN for both host and pathogen, and the subset of interspecies correlations, is presented as a tool for hypothesis generation and discovery for events in the early stages of fungal infection of Z. mays by A. flavus .

  9. Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

    Directory of Open Access Journals (Sweden)

    Marta Anna Szychlinska

    2016-03-01

    Full Text Available Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1 are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA, whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01. By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01. Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.

  10. The arabidopsis wall associated kinase-like 10 gene encodes a functional guanylyl cyclase and is co-expressed with pathogen defense related genes

    KAUST Repository

    Meier, Stuart

    2010-01-26

    Background: Second messengers have a key role in linking environmental stimuli to physiological responses. One such messenger, guanosine 3?,5?-cyclic monophosphate (cGMP), has long been known to be an essential signaling molecule in many different physiological processes in higher plants, including biotic stress responses. To date, however, the guanylyl cyclase (GC) enzymes that catalyze the formation of cGMP from GTP have largely remained elusive in higher plants. Principal Findings: We have identified an Arabidopsis receptor type wall associated kinase-like molecule (AtWAKL10) as a candidate GC and provide experimental evidence to show that the intracellular domain of AtWAKL10431-700 can generate cGMP in vitro. Further, we also demonstrate that the molecule has kinase activity indicating that AtWAKL10 is a twin-domain catalytic protein. A co-expression and stimulus-specific expression analysis revealed that AtWAKL10 is consistently coexpressed with well characterized pathogen defense related genes and along with these genes is induced early and sharply in response to a range of pathogens and their elicitors. Conclusions: We demonstrate that AtWAKL10 is a twin-domain, kinase-GC signaling molecule that may function in biotic stress responses that are critically dependent on the second messenger cGMP. © 2010 Meier et al.

  11. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Hudler, Petra [Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia); Komel, Radovan [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia)

    2009-10-28

    Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

  12. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

    Directory of Open Access Journals (Sweden)

    Hudler Petra

    2009-10-01

    Full Text Available Abstract Background Loss of DNA mismatch repair (MMR in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC. Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Methods Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. Results The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Conclusion Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

  13. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

    International Nuclear Information System (INIS)

    Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja; Hudler, Petra; Komel, Radovan

    2009-01-01

    Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene

  14. Comprehensive analysis of alternative splicing and functionality in neuronal differentiation of P19 cells.

    Directory of Open Access Journals (Sweden)

    Hitoshi Suzuki

    Full Text Available BACKGROUND: Alternative splicing, which produces multiple mRNAs from a single gene, occurs in most human genes and contributes to protein diversity. Many alternative isoforms are expressed in a spatio-temporal manner, and function in diverse processes, including in the neural system. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of the present study was to comprehensively investigate neural-splicing using P19 cells. GeneChip Exon Array analysis was performed using total RNAs purified from cells during neuronal cell differentiation. To efficiently and readily extract the alternative exon candidates, 9 filtering conditions were prepared, yielding 262 candidate exons (236 genes. Semiquantitative RT-PCR results in 30 randomly selected candidates suggested that 87% of the candidates were differentially alternatively spliced in neuronal cells compared to undifferentiated cells. Gene ontology and pathway analyses suggested that many of the candidate genes were associated with neural events. Together with 66 genes whose functions in neural cells or organs were reported previously, 47 candidate genes were found to be linked to 189 events in the gene-level profile of neural differentiation. By text-mining for the alternative isoform, distinct functions of the isoforms of 9 candidate genes indicated by the result of Exon Array were confirmed. CONCLUSIONS/SIGNIFICANCE: Alternative exons were successfully extracted. Results from the informatics analyses suggested that neural events were primarily governed by genes whose expression was increased and whose transcripts were differentially alternatively spliced in the neuronal cells. In addition to known functions in neural cells or organs, the uninvestigated alternative splicing events of 11 genes among 47 candidate genes suggested that cell cycle events are also potentially important. These genes may help researchers to differentiate the roles of alternative splicing in cell differentiation and cell

  15. Quantitative Evaluation for Differentiating Malignant and Benign Thyroid Nodules Using Histogram Analysis of Grayscale Sonograms.

    Science.gov (United States)

    Nam, Se Jin; Yoo, Jaeheung; Lee, Hye Sun; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kwak, Jin Young

    2016-04-01

    To evaluate the diagnostic value of histogram analysis using grayscale sonograms for differentiation of malignant and benign thyroid nodules. From July 2013 through October 2013, 579 nodules in 563 patients who had undergone ultrasound-guided fine-needle aspiration were included. For the grayscale histogram analysis, pixel echogenicity values in regions of interest were measured as 0 to 255 (0, black; 255, white) with in-house software. Five parameters (mean, skewness, kurtosis, standard deviation, and entropy) were obtained for each thyroid nodule. With principal component analysis, an index was derived. Diagnostic performance rates for the 5 histogram parameters and the principal component analysis index were calculated. A total of 563 patients were included in the study (mean age ± SD, 50.3 ± 12.3 years;range, 15-79 years). Of the 579 nodules, 431 were benign, and 148 were malignant. Among the 5 parameters and the principal component analysis index, the standard deviation (75.546 ± 14.153 versus 62.761 ± 16.01; P histogram analysis was feasible for differentiating malignant and benign thyroid nodules but did not show better diagnostic performance than subjective analysis performed by radiologists. Further technical advances will be needed to objectify interpretations of thyroid grayscale sonograms. © 2016 by the American Institute of Ultrasound in Medicine.

  16. Differentiating pheochromocytoma from lipid-poor adrenocortical adenoma by CT texture analysis: feasibility study.

    Science.gov (United States)

    Zhang, Gu-Mu-Yang; Shi, Bing; Sun, Hao; Jin, Zheng-Yu; Xue, Hua-Dan

    2017-09-01

    To investigate the feasibility of using CT texture analysis (CTTA) to differentiate pheochromocytoma from lipid-poor adrenocortical adenoma (lp-ACA). Ninety-eight pheochromocytomas and 66 lp-ACAs were included in this retrospective study. CTTA was performed on unenhanced and enhanced images. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different for the objective. Diagnostic accuracies were evaluated using the cutoff values of texture parameters with the highest AUCs. Compared to lp-ACAs, pheochromocytomas had significantly higher mean gray-level intensity (Mean), entropy, and mean of positive pixels (MPP), but lower skewness and kurtosis on unenhanced images (P feasible to use CTTA to differentiate pheochromocytoma from lp-ACA.

  17. Identification of the Causative Disease of Intermittent Claudication through Walking Motion Analysis: Feature Analysis and Differentiation

    Directory of Open Access Journals (Sweden)

    Tetsuyou Watanabe

    2014-01-01

    Full Text Available Intermittent claudication is a walking symptom. Patients with intermittent claudication experience lower limb pain after walking for a short time. However, rest relieves the pain and allows the patient to walk again. Unfortunately, this symptom predominantly arises from not 1 but 2 different diseases: LSS (lumber spinal canal stenosis and PAD (peripheral arterial disease. Patients with LSS can be subdivided by the affected vertebra into 2 main groups: L4 and L5. It is clinically very important to determine whether patients with intermittent claudication suffer from PAD, L4, or L5. This paper presents a novel SVM- (support vector machine- based methodology for such discrimination/differentiation using minimally required data, simple walking motion data in the sagittal plane. We constructed a simple walking measurement system that is easy to set up and calibrate and suitable for use by nonspecialists in small spaces. We analyzed the obtained gait patterns and derived input parameters for SVM that are also visually detectable and medically meaningful/consistent differentiation features. We present a differentiation methodology utilizing an SVM classifier. Leave-one-out cross-validation of differentiation/classification by this method yielded a total accuracy of 83%.

  18. Extending Differential Fault Analysis to Dynamic S-Box Advanced Encryption Standard Implementations

    Science.gov (United States)

    2014-09-18

    number. As a result decryption is a different function which relies on a different key to efficiently undo the work of encryption . RSA is the most...EXTENDING DIFFERENTIAL FAULT ANALYSIS TO DYNAMIC S-BOX ADVANCED ENCRYPTION STANDARD IMPLEMENTATIONS THESIS Bradley M. Flamm, Civilian AFIT-ENG-T-14-S...ADVANCED ENCRYPTION STANDARD IMPLEMENTATIONS THESIS Presented to the Faculty Department of Electrical and Computer Engineering Graduate School of

  19. Differentiation of Xylella fastidiosa Strains via Multilocus Sequence Analysis of Environmentally Mediated Genes (MLSA-E)

    OpenAIRE

    Parker, Jennifer K.; Havird, Justin C.; De La Fuente, Leonardo

    2012-01-01

    Isolates of the plant pathogen Xylella fastidiosa are genetically very similar, but studies on their biological traits have indicated differences in virulence and infection symptomatology. Taxonomic analyses have identified several subspecies, and phylogenetic analyses of housekeeping genes have shown broad host-based genetic differences; however, results are still inconclusive for genetic differentiation of isolates within subspecies. This study employs multilocus sequence analysis of enviro...

  20. histoneHMM: Differential analysis of histone modifications with broad genomic footprints

    Czech Academy of Sciences Publication Activity Database

    Heinig, M.; Colomé-Tatché, M.; Taudt, A.; Rintisch, C.; Schafer, S.; Pravenec, Michal; Hubner, N.; Vingron, M.; Johannes, F.

    2015-01-01

    Roč. 16, Feb 22 (2015), s. 60 ISSN 1471-2105 R&D Projects: GA MŠk(CZ) 7E10067; GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : ChIP - seq * histone modifications * Hidden Markov model * computational biology * differential analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.435, year: 2015

  1. Phytolith analysis for differentiating between foxtail millet (Setaria italica) and green foxtail (Setaria viridis).

    OpenAIRE

    Jianping Zhang; Houyuan Lu; Naiqin Wu; Xiaoyan Yang; Xianmin Diao

    2011-01-01

    Foxtail millet (Setaria italica) is one of the oldest domesticated cereal crops in Eurasia, but identifying foxtail millets, especially in charred grains, and differentiating it from its wild ancestor, green foxtail (Setaria viridis), in the archaeobotanical remains, is still problematic. Phytolithic analysis provides a meaningful method for identifying this important crop. In this paper, the silicon structure patterns in the glumes, lemmas, and paleas from inflorescence bracts in 16 modern p...

  2. Gram-negative and -positive bacteria differentiation in blood culture samples by headspace volatile compound analysis.

    Science.gov (United States)

    Dolch, Michael E; Janitza, Silke; Boulesteix, Anne-Laure; Graßmann-Lichtenauer, Carola; Praun, Siegfried; Denzer, Wolfgang; Schelling, Gustav; Schubert, Sören

    2016-12-01

    Identification of microorganisms in positive blood cultures still relies on standard techniques such as Gram staining followed by culturing with definite microorganism identification. Alternatively, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or the analysis of headspace volatile compound (VC) composition produced by cultures can help to differentiate between microorganisms under experimental conditions. This study assessed the efficacy of volatile compound based microorganism differentiation into Gram-negatives and -positives in unselected positive blood culture samples from patients. Headspace gas samples of positive blood culture samples were transferred to sterilized, sealed, and evacuated 20 ml glass vials and stored at -30 °C until batch analysis. Headspace gas VC content analysis was carried out via an auto sampler connected to an ion-molecule reaction mass spectrometer (IMR-MS). Measurements covered a mass range from 16 to 135 u including CO2, H2, N2, and O2. Prediction rules for microorganism identification based on VC composition were derived using a training data set and evaluated using a validation data set within a random split validation procedure. One-hundred-fifty-two aerobic samples growing 27 Gram-negatives, 106 Gram-positives, and 19 fungi and 130 anaerobic samples growing 37 Gram-negatives, 91 Gram-positives, and two fungi were analysed. In anaerobic samples, ten discriminators were identified by the random forest method allowing for bacteria differentiation into Gram-negative and -positive (error rate: 16.7 % in validation data set). For aerobic samples the error rate was not better than random. In anaerobic blood culture samples of patients IMR-MS based headspace VC composition analysis facilitates bacteria differentiation into Gram-negative and -positive.

  3. Deterministic factor analysis: methods of integro-differentiation of non-integral order

    Directory of Open Access Journals (Sweden)

    Valentina V. Tarasova

    2016-12-01

    Full Text Available Objective to summarize the methods of deterministic factor economic analysis namely the differential calculus and the integral method. nbsp Methods mathematical methods for integrodifferentiation of nonintegral order the theory of derivatives and integrals of fractional nonintegral order. Results the basic concepts are formulated and the new methods are developed that take into account the memory and nonlocality effects in the quantitative description of the influence of individual factors on the change in the effective economic indicator. Two methods are proposed for integrodifferentiation of nonintegral order for the deterministic factor analysis of economic processes with memory and nonlocality. It is shown that the method of integrodifferentiation of nonintegral order can give more accurate results compared with standard methods method of differentiation using the first order derivatives and the integral method using the integration of the first order for a wide class of functions describing effective economic indicators. Scientific novelty the new methods of deterministic factor analysis are proposed the method of differential calculus of nonintegral order and the integral method of nonintegral order. Practical significance the basic concepts and formulas of the article can be used in scientific and analytical activity for factor analysis of economic processes. The proposed method for integrodifferentiation of nonintegral order extends the capabilities of the determined factorial economic analysis. The new quantitative method of deterministic factor analysis may become the beginning of quantitative studies of economic agents behavior with memory hereditarity and spatial nonlocality. The proposed methods of deterministic factor analysis can be used in the study of economic processes which follow the exponential law in which the indicators endogenous variables are power functions of the factors exogenous variables including the processes

  4. Processing methods for differential analysis of LC/MS profile data

    Directory of Open Access Journals (Sweden)

    Orešič Matej

    2005-07-01

    Full Text Available Abstract Background Liquid chromatography coupled to mass spectrometry (LC/MS has been widely used in proteomics and metabolomics research. In this context, the technology has been increasingly used for differential profiling, i.e. broad screening of biomolecular components across multiple samples in order to elucidate the observed phenotypes and discover biomarkers. One of the major challenges in this domain remains development of better solutions for processing of LC/MS data. Results We present a software package MZmine that enables differential LC/MS analysis of metabolomics data. This software is a toolbox containing methods for all data processing stages preceding differential analysis: spectral filtering, peak detection, alignment and normalization. Specifically, we developed and implemented a new recursive peak search algorithm and a secondary peak picking method for improving already aligned results, as well as a normalization tool that uses multiple internal standards. Visualization tools enable comparative viewing of data across multiple samples. Peak lists can be exported into other data analysis programs. The toolbox has already been utilized in a wide range of applications. We demonstrate its utility on an example of metabolic profiling of Catharanthus roseus cell cultures. Conclusion The software is freely available under the GNU General Public License and it can be obtained from the project web page at: http://mzmine.sourceforge.net/.

  5. Advanced Poincaré plot analysis differentiates between hypertensive pregnancy disorders.

    Science.gov (United States)

    Seeck, A; Baumert, M; Fischer, C; Khandoker, A; Faber, R; Voss, A

    2011-10-01

    Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincaré plot analysis (PPA), the segmented Poincaré plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders.

  6. Differentiation of free-ranging chicken using discriminant analysis of phenotypic traits

    Directory of Open Access Journals (Sweden)

    Raed M. Al-Atiyat

    Full Text Available ABSTRACT In this study, we investigated the differentiation of five different chicken ecotypes - Center, North, South, West, and East - of Saudi Arabia using discriminate analysis. The analysis was based on nine important morphological and phenotypic traits: body color, beak color, earlobe color, eye color, shank color, comb color, comb type, comb size, and feather distribution. There was a strong significant relationship between the phenotype and effect of geographic height in terms of comb type and earlobe color in males as well as body, beak, eye, and shank color. In particular, the comb type and earlobe color differentiated the ecotypes of males. Among the females, the beak, earlobe, eye, shank color, and feather distribution had more differentiating power. Moreover, the discriminant analysis revealed that the five ecotypes were grouped into three clusters; the Center and the North in one cluster, the West and the South ecotypes in the second for males, and the East ecotype in the last cluster. The female dendogram branching was similar to the male dendrogram branching, except that the Center ecotype was grouped with the North instead of the South. The East ecotype was highly discriminated from the other ecotypes. Nevertheless, the potential of recent individual migration between ecotypes was also noted. Accordingly, the results of the utilized traits in this study might be effective in characterization and conservation of the genetic resources of the Saudi chicken.

  7. Advanced Poincaré plot analysis differentiates between hypertensive pregnancy disorders

    International Nuclear Information System (INIS)

    Seeck, A; Fischer, C; Voss, A; Baumert, M; Khandoker, A; Faber, R

    2011-01-01

    Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincaré plot analysis (PPA), the segmented Poincaré plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders

  8. Transcriptome Analysis of Flower Sex Differentiation in Jatropha curcas L. Using RNA Sequencing.

    Science.gov (United States)

    Xu, Gang; Huang, Jian; Yang, Yong; Yao, Yin-an

    2016-01-01

    Jatropha curcas is thought to be a promising biofuel material, but its yield is restricted by a low ratio of instaminate/staminate flowers (1/10-1/30). Furthermore, valuable information about flower sex differentiation in this plant is scarce. To explore the mechanism of this process in J. curcas, transcriptome profiling of flower development was carried out, and certain genes related with sex differentiation were obtained through digital gene expression analysis of flower buds from different phases of floral development. After Illumina sequencing and clustering, 57,962 unigenes were identified. A total of 47,423 unigenes were annotated, with 85 being related to carpel and stamen differentiation, 126 involved in carpel and stamen development, and 592 functioning in the later development stage for the maturation of staminate or instaminate flowers. Annotation of these genes provided comprehensive information regarding the sex differentiation of flowers, including the signaling system, hormone biosynthesis and regulation, transcription regulation and ubiquitin-mediated proteolysis. A further expression pattern analysis of 15 sex-related genes using quantitative real-time PCR revealed that gibberellin-regulated protein 4-like protein and AMP-activated protein kinase are associated with stamen differentiation, whereas auxin response factor 6-like protein, AGAMOUS-like 20 protein, CLAVATA1, RING-H2 finger protein ATL3J, auxin-induced protein 22D, and r2r3-myb transcription factor contribute to embryo sac development in the instaminate flower. Cytokinin oxidase, Unigene28, auxin repressed-like protein ARP1, gibberellin receptor protein GID1 and auxin-induced protein X10A are involved in both stages mentioned above. In addition to its function in the differentiation and development of the stamens, the gibberellin signaling pathway also functions in embryo sac development for the instaminate flower. The auxin signaling pathway also participates in both stamen development

  9. K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation

    DEFF Research Database (Denmark)

    Boecker, Werner; Stenman, Goeran; Loening, Thomas

    2013-01-01

    different cell lineages and define their cellular hierarchy in tumors with myoepithelial differentiation. isTILT analysis of a series of 28 breast, salivary, and lacrimal gland tumors, including pleomorphic adenomas (n=8), epithelial-myoepithelial tumors (n=9), and adenoid cystic carcinomas (n=11) revealed...... heterologeous cell differentiations such as squamous and mesenchymal progenies. p63 was co-expressed with K5/K14 in basal-like progenitor cells, myoepithelial, and squamous cells but not in glandular cells. Our results show that the corresponding counterpart tumors of breast and salivary/lacrimal glands have....... For that reason, we performed an in situ triple immunofluorescence lineage/differentiation tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA; myoepithelial marker) with the aim to construct and trace...

  10. Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

    International Nuclear Information System (INIS)

    Gao, Hua-Jun; Chen, Ya-Jing; Zuo, Duo; Xiao, Ming-Ming; Li, Ying; Guo, Hua; Zhang, Ning; Chen, Rui-Bing

    2015-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase B (MGAT5B) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC

  11. Analysis of mitochondrial function and localisation during human embryonic stem cell differentiation in vitro.

    Directory of Open Access Journals (Sweden)

    Andrew B J Prowse

    Full Text Available Human embryonic stem cell (hESC derivatives show promise as viable cell therapy options for multiple disorders in different tissues. Recent advances in stem cell biology have lead to the reliable production and detailed molecular characterisation of a range of cell-types. However, the role of mitochondria during differentiation has yet to be fully elucidated. Mitochondria mediate a cells response to altered energy requirements (e.g. cardiomyocyte contraction and, as such, the mitochondrial phenotype is likely to change during the dynamic process of hESC differentiation. We demonstrate that manipulating mitochondrial biogenesis alters mesendoderm commitment. To investigate mitochondrial localisation during early lineage specification of hESCs we developed a mitochondrial reporter line, KMEL2, in which sequences encoding the green fluorescent protein (GFP are targeted to the mitochondria. Differentiation of KMEL2 lines into the three germ layers showed that the mitochondria in these differentiated progeny are GFP positive. Therefore, KMEL2 hESCs facilitate the study of mitochondria in a range of cell types and, importantly, permit real-time analysis of mitochondria via the GFP tag.

  12. Recent applications of harmonic analysis to function spaces, differential equations, and data science novel methods in harmonic analysis

    CERN Document Server

    Gia, Quoc; Mayeli, Azita; Mhaskar, Hrushikesh; Zhou, Ding-Xuan

    2017-01-01

    The second of a two volume set on novel methods in harmonic analysis, this book draws on a number of original research and survey papers from well-known specialists detailing the latest innovations and recently discovered links between various fields. Along with many deep theoretical results, these volumes contain numerous applications to problems in signal processing, medical imaging, geodesy, statistics, and data science. The chapters within cover an impressive range of ideas from both traditional and modern harmonic analysis, such as: the Fourier transform, Shannon sampling, frames, wavelets, functions on Euclidean spaces, analysis on function spaces of Riemannian and sub-Riemannian manifolds, Fourier analysis on manifolds and Lie groups, analysis on combinatorial graphs, sheaves, co-sheaves, and persistent homologies on topological spaces. Volume II is organized around the theme of recent applications of harmonic analysis to function spaces, differential equations, and data science, covering topics such a...

  13. Thermo Gravimetric and Differential Thermal Analysis of Clay of Western Rajasthan (india)

    Science.gov (United States)

    Shekhawat, M. S.

    The paper presents the study of thermo gravimetric and differential thermal analysis of blended clay. Western part of Rajasthan (India) is rich resource of Ball clays and it is mainly used by porcelain, sanitary ware, and tile industry. The quality and grade of clay available in the region vary from one deposit to other. To upgrade the fired colour and strength properties, different variety of clays may be blended together. The paper compares the results of thermal analysis one of blended clay B2 with reference clay of Ukraine which is imported by industries owners. The result revealed that the blended clay is having mineral kaolinite while the Ukrainian clay is Halloysite.

  14. Global similarity and local divergence in human and mouse gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-09-01

    Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

  15. Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a 'function follows form' model of differentiation.

    Science.gov (United States)

    Kankeu, Cynthia; Clarke, Kylie; Van Haver, Delphi; Gevaert, Kris; Impens, Francis; Dittrich, Anna; Roderick, H Llewelyn; Passante, Egle; Huber, Heinrich J

    2018-05-17

    The rat cardiomyoblast cell line H9C2 has emerged as a valuable tool for studying cardiac development, mechanisms of disease and toxicology. We present here a rigorous proteomic analysis that monitored the changes in protein expression during differentiation of H9C2 cells into cardiomyocyte-like cells over time. Quantitative mass spectrometry followed by gene ontology (GO) enrichment analysis revealed that early changes in H9C2 differentiation are related to protein pathways of cardiac muscle morphogenesis and sphingolipid synthesis. These changes in the proteome were followed later in the differentiation time-course by alterations in the expression of proteins involved in cation transport and beta-oxidation. Studying the temporal profile of the H9C2 proteome during differentiation in further detail revealed eight clusters of co-regulated proteins that can be associated with early, late, continuous and transient up- and downregulation. Subsequent reactome pathway analysis based on these eight clusters further corroborated and detailed the results of the GO analysis. Specifically, this analysis confirmed that proteins related to pathways in muscle contraction are upregulated early and transiently, and proteins relevant to extracellular matrix organization are downregulated early. In contrast, upregulation of proteins related to cardiac metabolism occurs at later time points. Finally, independent validation of the proteomics results by immunoblotting confirmed hereto unknown regulators of cardiac structure and ionic metabolism. Our results are consistent with a 'function follows form' model of differentiation, whereby early and transient alterations of structural proteins enable subsequent changes that are relevant to the characteristic physiology of cardiomyocytes.

  16. THE DIDACTIC ANALYSIS OF STUDIES ON THE INVERSE PROBLEMS FOR THE DIFFERENTIAL EQUATIONS

    Directory of Open Access Journals (Sweden)

    В С Корнилов

    2017-12-01

    Full Text Available In article results of the didactic analysis of the organization and carrying out seminar classes in the inverse problems for the differential equations for students of higher educational institutions of the physical and mathematical directions of preparation are discussed. Such analysis includes a general characteristic of mathematical content of seminar occupations, the analysis of structure of seminar occupation, the analysis of realization of the developing and educational purposes, allocation of didactic units and informative means which have to be acquired by students when training each section of content of training in the inverse problems and other important psychology and pedagogical aspects. The attention to establishment of compliance to those of seminar occupations to lecture material and identification of functions in teaching and educational process which are carried out at the solution of the inverse problems, and also is paid to need to show various mathematical receptions and methods of their decision. Such didactic analysis helps not only to reveal such inverse problems at which solution students can collectively join in creative process of search of their decision, but also effectively organize control of assimilation of knowledge and abilities of students on the inverse problems for the differential equations.

  17. Cell kinetics, DNA integrity, differentiation, and lipid fingerprinting analysis of rabbit adipose-derived stem cells.

    Science.gov (United States)

    Barretto, Letícia Siqueira de Sá; Lessio, Camila; Sawaki e Nakamura, Ahy Natally; Lo Turco, Edson Guimarães; da Silva, Camila Gonzaga; Zambon, João Paulo; Gozzo, Fábio César; Pilau, Eduardo Jorge; de Almeida, Fernando Gonçalves

    2014-10-01

    Human adipose tissue has been described as a potential alternative reservoir for stem cells. Although studies have been performed in rabbits using autologous adipose-derived stem cells (ADSC), these cells have not been well characterized. The primary objectives of this study were to demonstrate the presence of adipose-derived stem cells isolated from rabbit inguinal fat pads and to characterize them through osteogenic and adipogenic in vitro differentiation and lipid fingerprinting analysis. The secondary objective was to evaluate cell behavior through growth kinetics, cell viability, and DNA integrity. Rabbit ADSCs were isolated to determine the in vitro growth kinetics and cell viability. DNA integrity was assessed by an alkaline Comet assay in passages 0 and 5. The osteogenic differentiation was evaluated by Von Kossa, and Alizarin Red S staining and adipogenic differentiation were assessed by Oil Red O staining. Lipid fingerprinting analyses of control, adipogenic, and osteogenic differentiated cells were performed by MALDI-TOF/MS. We demonstrate that rabbit ADSC have a constant growth rate at the early passages, with increased DNA fragmentation at or after passage 5. Rabbit ADSC viability was similar in passages 2 and 5 (90.7% and 86.6%, respectively), but there was a tendency to decreased cellular growth rate after passage 3. The ADSC were characterized by the expression of surface markers such as CD29 (67.4%) and CD44 (89.4%), using CD 45 (0.77%) as a negative control. ADSC from rabbits were successfully isolated form the inguinal region. These cells were capable to differentiate into osteogenic and adipogenic tissue when they were placed in inductive media. After each passage, there was a trend towards decreased cell growth. On the other hand, DNA fragmentation increased at each passage. ADSC had a different lipid profile when placed in control, adipogenic, or osteogenic media.

  18. A comparative study of techniques for differential expression analysis on RNA-Seq data.

    Directory of Open Access Journals (Sweden)

    Zong Hong Zhang

    Full Text Available Recent advances in next-generation sequencing technology allow high-throughput cDNA sequencing (RNA-Seq to be widely applied in transcriptomic studies, in particular for detecting differentially expressed genes between groups. Many software packages have been developed for the identification of differentially expressed genes (DEGs between treatment groups based on RNA-Seq data. However, there is a lack of consensus on how to approach an optimal study design and choice of suitable software for the analysis. In this comparative study we evaluate the performance of three of the most frequently used software tools: Cufflinks-Cuffdiff2, DESeq and edgeR. A number of important parameters of RNA-Seq technology were taken into consideration, including the number of replicates, sequencing depth, and balanced vs. unbalanced sequencing depth within and between groups. We benchmarked results relative to sets of DEGs identified through either quantitative RT-PCR or microarray. We observed that edgeR performs slightly better than DESeq and Cuffdiff2 in terms of the ability to uncover true positives. Overall, DESeq or taking the intersection of DEGs from two or more tools is recommended if the number of false positives is a major concern in the study. In other circumstances, edgeR is slightly preferable for differential expression analysis at the expense of potentially introducing more false positives.

  19. High content analysis of differentiation and cell death in human adipocytes.

    Science.gov (United States)

    Doan-Xuan, Quang Minh; Sarvari, Anitta K; Fischer-Posovszky, Pamela; Wabitsch, Martin; Balajthy, Zoltan; Fesus, Laszlo; Bacso, Zsolt

    2013-10-01

    Understanding adipocyte biology and its homeostasis is in the focus of current obesity research. We aimed to introduce a high-content analysis procedure for directly visualizing and quantifying adipogenesis and adipoapoptosis by laser scanning cytometry (LSC) in a large population of cell. Slide-based image cytometry and image processing algorithms were used and optimized for high-throughput analysis of differentiating cells and apoptotic processes in cell culture at high confluence. Both preadipocytes and adipocytes were simultaneously scrutinized for lipid accumulation, texture properties, nuclear condensation, and DNA fragmentation. Adipocyte commitment was found after incubation in adipogenic medium for 3 days identified by lipid droplet formation and increased light absorption, while terminal differentiation of adipocytes occurred throughout day 9-14 with characteristic nuclear shrinkage, eccentric nuclei localization, chromatin condensation, and massive lipid deposition. Preadipocytes were shown to be more prone to tumor necrosis factor alpha (TNFα)-induced apoptosis compared to mature adipocytes. Importantly, spontaneous DNA fragmentation was observed at early stage when adipocyte commitment occurs. This DNA damage was independent from either spontaneous or induced apoptosis and probably was part of the differentiation program. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

  20. Genetic diversity and geographic differentiation analysis of duckweed using inter-simple sequence repeat markers.

    Science.gov (United States)

    Xue, Huiling; Xiao, Yao; Jin, Yanling; Li, Xinbo; Fang, Yang; Zhao, Hai; Zhao, Yun; Guan, Jiafa

    2012-01-01

    Duckweed, with rapid growth rate and high starch content, is a new alternate feedstock for bioethanol production. The genetic diversity among 27 duckweed populations of seven species in genus Lemna and Spirodela from China and Vietnam was analyzed by ISSR-PCR. Eight ISSR primers generating a reproducible amplification banding pattern had been screened. 89 polymorphic bands were scored out of the 92 banding patterns of 16 Lemna populations, accounting for 96.74% of the polymorphism. 98 polymorphic bands of 11 Spirodela populations were scored out of 99 banding patterns, and the polymorphism was 98.43%. The genetic distance of Lemna varied from 0.127 to 0.784, and from 0.138 to 0.902 for Spirodela, which indicated a high level of genetic variation among the populations studied. The unweighted pair group method with arithmetic average (UPGMA) cluster analysis corresponded well with the genetic distance. Populations from Sichuan China grouped together and so did the populations from Vietnam, which illuminated populations collected from the same region clustered into one group. Especially, the only one population from Tibet was included in subgroup A2 alone. Clustering analysis indicated that the geographic differentiation of collected sites correlated closely with the genetic differentiation of duckweeds. The results suggested that geographic differentiation had great influence on genetic diversity of duckweed in China and Vietnam at the regional scale. This study provided primary guidelines for collection, conservation, characterization of duckweed resources for bioethanol production etc.

  1. Vibration analysis of Euler-Bernoulli beam with open cracks on elastic foundations using differential transformation method and generalized differential quadrature method

    International Nuclear Information System (INIS)

    Shin, Young Jae; Hwang, Ki Sup; Yun, Jong Hak

    2006-01-01

    The main purpose of this paper is to apply Differential Transformation Method(DTM) and Generalized Differential Quadrature Method(GDQM) to vibration analysis of Euler-Bernoulli beam with open cracks on elastic foundation. In this paper the concepts of DTM and GDQM were briefly introduced. The governing equation of motion of the beam with open cracks on elastic foundation is derived. The cracks are modeled by massless substitute spring. The effects of the crack location, size and the foundation constants, on the natural frequencies of the beam, are investigated. Numerical calculations are carried out and compared with previous published results

  2. Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors

    Directory of Open Access Journals (Sweden)

    Lamblin Anne-Francoise

    2007-10-01

    Full Text Available Abstract Background Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs, which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin. Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation. Results To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1, sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4 were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1 were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway. Conclusion This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that

  3. Evaluation of shear wave elastography for differential diagnosis of breast lesions: A new qualitative analysis versus conventional quantitative analysis.

    Science.gov (United States)

    Ren, Wei-Wei; Li, Xiao-Long; Wang, Dan; Liu, Bo-Ji; Zhao, Chong-Ke; Xu, Hui-Xiong

    2018-04-13

    To evaluate a special kind of ultrasound (US) shear wave elastography for differential diagnosis of breast lesions, using a new qualitative analysis (i.e. the elasticity score in the travel time map) compared with conventional quantitative analysis. From June 2014 to July 2015, 266 pathologically proven breast lesions were enrolled in this study. The maximum, mean, median, minimum, and standard deviation of shear wave speed (SWS) values (m/s) were assessed. The elasticity score, a new qualitative feature, was evaluated in the travel time map. The area under the receiver operating characteristic (AUROC) curves were plotted to evaluate the diagnostic performance of both qualitative and quantitative analyses for differentiation of breast lesions. Among all quantitative parameters, SWS-max showed the highest AUROC (0.805; 95% CI: 0.752, 0.851) compared with SWS-mean (0.786; 95% CI:0.732, 0.834; P = 0.094), SWS-median (0.775; 95% CI:0.720, 0.824; P = 0.046), SWS-min (0.675; 95% CI:0.615, 0.731; P = 0.000), and SWS-SD (0.768; 95% CI:0.712, 0.817; P = 0.074). The AUROC of qualitative analysis in this study obtained the best diagnostic performance (0.871; 95% CI: 0.825, 0.909, compared with the best parameter of SWS-max in quantitative analysis, P = 0.011). The new qualitative analysis of shear wave travel time showed the superior diagnostic performance in the differentiation of breast lesions in comparison with conventional quantitative analysis.

  4. Stability analysis for a delay differential equations model of a hydraulic turbine speed governor

    Science.gov (United States)

    Halanay, Andrei; Safta, Carmen A.; Dragoi, Constantin; Piraianu, Vlad F.

    2017-01-01

    The paper aims to study the dynamic behavior of a speed governor for a hydraulic turbine using a mathematical model. The nonlinear mathematical model proposed consists in a system of delay differential equations (DDE) to be compared with already established mathematical models of ordinary differential equations (ODE). A new kind of nonlinearity is introduced as a time delay. The delays can characterize different running conditions of the speed governor. For example, it is considered that spool displacement of hydraulic amplifier might be blocked due to oil impurities in the oil supply system and so the hydraulic amplifier has a time delay in comparison to the time control. Numerical simulations are presented in a comparative manner. A stability analysis of the hydraulic control system is performed, too. Conclusions of the dynamic behavior using the DDE model of a hydraulic turbine speed governor are useful in modeling and controlling hydropower plants.

  5. Analysis on expression of gene for flower shape in Dendrobium sonia mutants using differential display technique

    International Nuclear Information System (INIS)

    Affrida Abu Hassan; Ahmad Syazni Kamarudin; Nurul Nadia Aminuddin; Mohd Nazir Basiran

    2004-01-01

    In vitro mutagenesis on Dendrobium Sonia in MINT has produced mutants with wide range of flower form and colour variations. Among the mutants are plants with different flower size and shape. These changes could be caused by alterations to the expression level of the genes responsible for the characteristics. In this studies, Differential Display technique was used to identify and analyse altered gene expression at the mRNA level. Total RNA of the control and mutants were reversed transcribed using three anchored oligo-d T primers. Subsequently, these cDNAs were Pcr amplified in combination with 16 arbitrary primers. The amplified products were electrophoresed side by side on agarose gel. Differentially expressed bands are isolated for further analysis. (Author)

  6. Differentiation of Vitis vinifera varieties by MALDI-MS analysis of the grape seed proteins.

    Science.gov (United States)

    Pesavento, Ivana Chiara; Bertazzo, Antonella; Flamini, Riccardo; Vedova, Antonio Dalla; De Rosso, Mirko; Seraglia, Roberta; Traldi, Pietro

    2008-02-01

    Until now the study of pathogenic related proteins in grape juice and wine, performed by ESI-MS, LC/ESI-MS, and MALDI/MS, has been proposed for differentiation of varieties. In fact, chitinases and thaumatin-like proteins persist through the vinification process and cause hazes and sediments in bottled wines. An additional instrument, potentially suitable for the grape varieties differentiation, has been developed by MALDI/MS for the grape seed protein analysis. The hydrosoluble protein profiles of seeds extract from three different Vitis vinifera grape (red and white) varieties were analyzed and compared. In order to evaluate the environmental conditions and harvest effects, the seed protein profiles of one grape variety from different locations and harvests were studied. (c) 2008 John Wiley & Sons, Ltd.

  7. Assessment of textural differentiations in forest resources in Romania using fractal analysis

    DEFF Research Database (Denmark)

    Andronache, Ion; Fensholt, Rasmus; Ahammer, Helmut

    2017-01-01

    regions in Romania affected by both deforestation and reforestation using a non-Euclidean method based on fractal analysis.We calculated four fractal dimensions of forest areas: the fractal box-counting dimension of the forest areas, the fractal box-counting dimension of the dilated forest areas......, the fractal dilation dimension and the box-counting dimension of the border of the dilated forest areas. Fractal analysis revealed morpho-structural and textural differentiations of forested, deforested and reforested areas in development regions with dominant mountain relief and high hills (more forested...... and compact organization) in comparison to the development regions dominated by plains or low hills (less forested, more fragmented with small and isolated clusters). Our analysis used the fractal analysis that has the advantage of analyzing the entire image, rather than studying local information, thereby...

  8. Matrix Analysis of Traditional Chinese Medicine Differential Diagnoses in Gulf War Illness.

    Science.gov (United States)

    Taylor-Swanson, Lisa; Chang, Joe; Schnyer, Rosa; Hsu, Kai-Yin; Schmitt, Beth Ann; Conboy, Lisa A

    2018-03-08

    To qualitatively categorize Traditional Chinese Medicine (TCM) differential diagnoses in a sample of veterans with Gulf War Illness (GWI) pre- and postacupuncture treatment. The authors randomized 104 veterans diagnosed with GWI to a 6-month acupuncture intervention that consisted of either weekly or biweekly individualized acupuncture treatments. TCM differential diagnoses were recorded at baseline and at 6 months. These TCM diagnoses were evaluated using Matrix Analysis to determine co-occurring patterns of excess, deficiency, and channel imbalances. These diagnoses were examined within and between participants to determine patterns of change and to assess stability of TCM diagnoses over time. Frequencies of diagnoses of excess, deficiency, and channel patterns were tabulated. Diagnoses of excess combined with deficiency decreased from 43% at baseline to 39% of the sample at 6 months. Excess+deficiency+channel imbalances decreased from 26% to 17%, while deficiency+channel imbalances decreased from 11% to 4% over the study duration. The authors observed a trend over time of decreased numbers of individuals presenting with all three types of differential diagnosis combinations. This may suggest that fewer people were diagnosed with concurrent excess, deficiency, and channel imbalances and perhaps a lessening in the complexity of their presentation. This is the first published article that organizes and defines TCM differential diagnoses using Matrix Analysis; currently, there are no TCM frameworks for GWI. These findings are preliminary given the sample size and the amount of missing data at 6 months. Characterization of the TCM clinical presentation of veterans suffering from GWI may help us better understand the potential role that East Asian medicine may play in managing veterans with GWI and the design of effective acupuncture treatments based on TCM. The development of a TCM manual for treating GWI is merited.

  9. Target genes prediction and functional analysis of microRNAs differentially expressed in gastric cancer stem cells MKN-45

    Directory of Open Access Journals (Sweden)

    Zohreh Salehi

    2017-01-01

    Conclusions: Bioinformatics analysis such as DAVID database, GO biological process, GO molecular function, Kyoto encyclopedia of genes and genomes pathways, BioCarta pathway, Panther pathway, and Reactome pathway revealed that target genes of differentially expressed miRNAs in gastric CSCs were connected to pivotal biological pathways that involved in cell cycle regulation, stemness properties, and differentiation.

  10. The analysis of fractional differential equations an application-oriented exposition using differential operators of Caputo type

    CERN Document Server

    Diethelm, Kai

    2010-01-01

    Fractional calculus was first developed by pure mathematicians in the middle of the 19th century. Some 100 years later, engineers and physicists have found applications for these concepts in their areas. However there has traditionally been little interaction between these two communities. In particular, typical mathematical works provide extensive findings on aspects with comparatively little significance in applications, and the engineering literature often lacks mathematical detail and precision. This book bridges the gap between the two communities. It concentrates on the class of fractional derivatives most important in applications, the Caputo operators, and provides a self-contained, thorough and mathematically rigorous study of their properties and of the corresponding differential equations. The text is a useful tool for mathematicians and researchers from the applied sciences alike. It can also be used as a basis for teaching graduate courses on fractional differential equations.

  11. Integrated analysis of hematopoietic differentiation outcomes and molecular characterization reveals unbiased differentiation capacity and minor transcriptional memory in HPC/HSC-iPSCs.

    Science.gov (United States)

    Gao, Shuai; Hou, Xinfeng; Jiang, Yonghua; Xu, Zijian; Cai, Tao; Chen, Jiajie; Chang, Gang

    2017-01-23

    Transcription factor-mediated reprogramming can reset the epigenetics of somatic cells into a pluripotency compatible state. Recent studies show that induced pluripotent stem cells (iPSCs) always inherit starting cell-specific characteristics, called epigenetic memory, which may be advantageous, as directed differentiation into specific cell types is still challenging; however, it also may be unpredictable when uncontrollable differentiation occurs. In consideration of biosafety in disease modeling and personalized medicine, the availability of high-quality iPSCs which lack a biased differentiation capacity and somatic memory could be indispensable. Herein, we evaluate the hematopoietic differentiation capacity and somatic memory state of hematopoietic progenitor and stem cell (HPC/HSC)-derived-iPSCs (HPC/HSC-iPSCs) using a previously established sequential reprogramming system. We found that HPC/HSCs are amenable to being reprogrammed into iPSCs with unbiased differentiation capacity to hematopoietic progenitors and mature hematopoietic cells. Genome-wide analyses revealed that no global epigenetic memory was detectable in HPC/HSC-iPSCs, but only a minor transcriptional memory of HPC/HSCs existed in a specific tetraploid complementation (4 N)-incompetent HPC/HSC-iPSC line. However, the observed minor transcriptional memory had no influence on the hematopoietic differentiation capacity, indicating the reprogramming of the HPC/HSCs was nearly complete. Further analysis revealed the correlation of minor transcriptional memory with the aberrant distribution of H3K27me3. This work provides a comprehensive framework for obtaining high-quality iPSCs from HPC/HSCs with unbiased hematopoietic differentiation capacity and minor transcriptional memory.

  12. [Analysis of tissue-specific differentially methylated genes with differential gene expression in non-small cell lung cancer].

    Science.gov (United States)

    Yin, L G; Zou, Z Q; Zhao, H Y; Zhang, C L; Shen, J G; Qi, L; Qi, M; Xue, Z Q

    2014-01-01

    Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non-small cell lung carcinomas which are regarded as the leading cause of cancer-related malignancy worldwide. The aim of this study is to detect the differentially methylated loci (DMLs) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression level of specific methylated genes. Using TCGA database and Illumina HumanMethylation 27 arrays, we first screened the DMGs and DMLs in tumor samples. Then, we explored the BiologicalProcess terms of hypermethylated and hypomethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in CpG-island, whereas hypomethylation was located in non-CpG-island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependenit regulation of transcription, and hypomethylated genes mainly 'enriched in the term of immune responses. Additionally, the expression level of specific differentially methylated genesis distinctbetween ADC and SCC. It is concluded that ADC and SCC have different methylated status that might play an important role in carcinogenesis.

  13. CoLIde: a bioinformatics tool for CO-expression-based small RNA Loci Identification using high-throughput sequencing data.

    Science.gov (United States)

    Mohorianu, Irina; Stocks, Matthew Benedict; Wood, John; Dalmay, Tamas; Moulton, Vincent

    2013-07-01

    Small RNAs (sRNAs) are 20-25 nt non-coding RNAs that act as guides for the highly sequence-specific regulatory mechanism known as RNA silencing. Due to the recent increase in sequencing depth, a highly complex and diverse population of sRNAs in both plants and animals has been revealed. However, the exponential increase in sequencing data has also made the identification of individual sRNA transcripts corresponding to biological units (sRNA loci) more challenging when based exclusively on the genomic location of the constituent sRNAs, hindering existing approaches to identify sRNA loci. To infer the location of significant biological units, we propose an approach for sRNA loci detection called CoLIde (Co-expression based sRNA Loci Identification) that combines genomic location with the analysis of other information such as variation in expression levels (expression pattern) and size class distribution. For CoLIde, we define a locus as a union of regions sharing the same pattern and located in close proximity on the genome. Biological relevance, detected through the analysis of size class distribution, is also calculated for each locus. CoLIde can be applied on ordered (e.g., time-dependent) or un-ordered (e.g., organ, mutant) series of samples both with or without biological/technical replicates. The method reliably identifies known types of loci and shows improved performance on sequencing data from both plants (e.g., A. thaliana, S. lycopersicum) and animals (e.g., D. melanogaster) when compared with existing locus detection techniques. CoLIde is available for use within the UEA Small RNA Workbench which can be downloaded from: http://srna-workbench.cmp.uea.ac.uk.

  14. Analysis of Zr++++ dan ZrO++ cations through their Hydroxide precipitate with thermal differential analysis method

    International Nuclear Information System (INIS)

    Simbolon, Sahat; Ratmi-Herlani

    1996-01-01

    Hydroxide of zirconyl and zirconium, made by reacting zirconium and zirconyl solution with NH 4 OH 25 % solution, were analysed by thermal differential analysis (TDA). It was also done TDA method for hydroxide of zirconyl and zirconium, made by reacting zirconyl chloride and zirconium chloride solid with NH 4 OH 25 % solution directly. It was found that TDA of hydroxide precipitate made through solution had a clear TDA counter, meanwhile TDA thermogram of hydroxide precipitate made by direct adding NH 4 OH 25 % solution to zirconyl and zirconium hydroxide had no clear TDA thermogram. Precipitate Zr O(OH) 2 and Zr(OH) 4 found through solution could be differentiated each other based on their TDA thermograms

  15. Functional network analysis of genes differentially expressed during xylogenesis in soc1ful woody Arabidopsis plants.

    Science.gov (United States)

    Davin, Nicolas; Edger, Patrick P; Hefer, Charles A; Mizrachi, Eshchar; Schuetz, Mathias; Smets, Erik; Myburg, Alexander A; Douglas, Carl J; Schranz, Michael E; Lens, Frederic

    2016-06-01

    Many plant genes are known to be involved in the development of cambium and wood, but how the expression and functional interaction of these genes determine the unique biology of wood remains largely unknown. We used the soc1ful loss of function mutant - the woodiest genotype known in the otherwise herbaceous model plant Arabidopsis - to investigate the expression and interactions of genes involved in secondary growth (wood formation). Detailed anatomical observations of the stem in combination with mRNA sequencing were used to assess transcriptome remodeling during xylogenesis in wild-type and woody soc1ful plants. To interpret the transcriptome changes, we constructed functional gene association networks of differentially expressed genes using the STRING database. This analysis revealed functionally enriched gene association hubs that are differentially expressed in herbaceous and woody tissues. In particular, we observed the differential expression of genes related to mechanical stress and jasmonate biosynthesis/signaling during wood formation in soc1ful plants that may be an effect of greater tension within woody tissues. Our results suggest that habit shifts from herbaceous to woody life forms observed in many angiosperm lineages could have evolved convergently by genetic changes that modulate the gene expression and interaction network, and thereby redeploy the conserved wood developmental program. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  16. FIDEA: a server for the functional interpretation of differential expression analysis.

    KAUST Repository

    D'Andrea, Daniel

    2013-06-10

    The results of differential expression analyses provide scientists with hundreds to thousands of differentially expressed genes that need to be interpreted in light of the biology of the specific system under study. This requires mapping the genes to functional classifications that can be, for example, the KEGG pathways or InterPro families they belong to, their GO Molecular Function, Biological Process or Cellular Component. A statistically significant overrepresentation of one or more category terms in the set of differentially expressed genes is an essential step for the interpretation of the biological significance of the results. Ideally, the analysis should be performed by scientists who are well acquainted with the biological problem, as they have a wealth of knowledge about the system and can, more easily than a bioinformatician, discover less obvious and, therefore, more interesting relationships. To allow experimentalists to explore their data in an easy and at the same time exhaustive fashion within a single tool and to test their hypothesis quickly and effortlessly, we developed FIDEA. The FIDEA server is located at http://www.biocomputing.it/fidea; it is free and open to all users, and there is no login requirement.

  17. Molecular and Genetic Analysis of Hormone-Regulated Differential Cell Elongation in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Joseph R.

    2002-12-03

    The authors have utilized the response of Arabidopsis seedlings to the plant hormone ethylene to identify new genes involved in the regulation of ethylene biosynthesis, perception, signal transduction and differential cell growth. In building a genetic framework for the action of these genes, they developed a molecular model that has facilitated the understanding of the molecular requirements of ethylene for cell elongation processes. The ethylene response pathway in Arabidopsis appears to be primarily linear and is defined by the genes: ETR1, ETR2, ERS1, ERS2, EIN4, CTR1, EIN2, EIN3, EIN5 EIN6, and EIN. Downstream branches identified by the HLS1, EIR1, and AUX1 genes involve interactions with other hormonal (auxin) signals in the process of differential cell elongation in the hypocotyl hook. Cloning and characterization of HLS1 and three HLS1-LIKE genes in the laboratory has been supported under this award. HLS1 is required for differential elongation of cells in the hypocotyl and may act in the establishment of hormone gradients. Also during the award period, they have identified and begun preliminary characterization of two genes that genetically act upstream of the ethylene receptors. ETO1 and RAN1 encode negative regulators of ethylene biosynthesis and signaling respectively. Progress on the analysis of these genes along with HOOKLESS1 is described.

  18. Analysis of genetic diversity and differentiation of seven stocks of Litopenaeus vannamei using microsatellite markers

    Science.gov (United States)

    Zhang, Kai; Wang, Weiji; Li, Weiya; Zhang, Quanqi; Kong, Jie

    2014-08-01

    Seven microsatellite markers were used to evaluate the genetic diversity and differentiation of seven stocks of Litopenaeus vannamei, which were introduced from Central and South America to China. All seven microsatellite loci were polymorphic, with polymorphism information content ( PIC) values ranging from 0.593 to 0.952. Totally 92 alleles were identified, and the number of alleles ( Na) and effective alleles ( Ne) varied between 4 and 21 and 2.7 and 14.6, respectively. Observed heterozygosity ( H o) values were lower than the expected heterozygosity ( H e) values (0.526-0.754), which indicated that the seven stocks possessed a rich genetic diversity. Thirty-seven tests were detected for reasonable significant deviation from Hardy-Weinberg equilibrium. F is values were positive at five loci, suggesting that there was a relatively high degree of inbreeding within stocks. Pairwise F st values ranged from 0.0225 to 0.151, and most of the stock pairs were moderately differentiated. Genetic distance and cluster analysis using UPGMA revealed a close genetic relationship of L. vannamei between Pop2 and Pop3. AMOVA indicated that the genetic variation among stocks (11.3%) was much lower than that within stocks (88.7%). Although the seven stocks had a certain degree of genetic differentiation and a rich genetic diversity, there is an increasing risk of decreased performance due to inbreeding in subsequent generations.

  19. Comparative proteomic analysis of differentially expressed proteins in the urine of reservoir hosts of leptospirosis.

    Directory of Open Access Journals (Sweden)

    Jarlath E Nally

    Full Text Available Rattus norvegicus is a natural reservoir host for pathogenic species of Leptospira. Experimentally infected rats remain clinically normal, yet persistently excrete large numbers of leptospires from colonized renal tubules via urine, despite a specific host immune response. Whilst persistent renal colonization and shedding is facilitated in part by differential antigen expression by leptospires to evade host immune responses, there is limited understanding of kidney and urinary proteins expressed by the host that facilitates such biological equilibrium. Urine pellets were collected from experimentally infected rats shedding leptospires and compared to urine from non-infected controls spiked with in vitro cultivated leptospires for analysis by 2-D DIGE. Differentially expressed host proteins include membrane metallo endopeptidase, napsin A aspartic peptidase, vacuolar H+ATPase, kidney aminopeptidase and immunoglobulin G and A. Loa22, a virulence factor of Leptospira, as well as the GroEL, were increased in leptospires excreted in urine compared to in vitro cultivated leptospires. Urinary IgG from infected rats was specific for leptospires. Results confirm differential protein expression by both host and pathogen during chronic disease and include markers of kidney function and immunoglobulin which are potential biomarkers of infection.

  20. Investigation of Thermal Behavior for Natural Fibres Reinforced Epoxy using Thermogravimetric and Differential Scanning Calorimetric Analysis

    Directory of Open Access Journals (Sweden)

    Fauzi F.A.

    2016-01-01

    Full Text Available This paper presented the research works on the investigation of the thermal behavior of the natural fibres; i.e. pineapple leaf fibre, kenaf fibre and mengkuang fibres reinforced epoxy. The thermogravimetric analysis and differential scanning calorimetric analysis were used to measure the thermal behavior of the treated and untreated pineapple, kenaf and mengkuang fibres reinforced epoxy. The samples for both analysis were subjected to maximum temperature 600°C at the heating rate of 10°C/min. The results showed that the treated fibres show higher maximum peak temperature as compared to the untreated fibres. Additionally, the glass transition temperature showed a lower value for all treated fibre. It can be concluded that investigation of thermal properties of these natural fibres could improve the utilization of natural fibre composites in various applications i.e. sports applications.

  1. Opsin expression in Limulus eyes: a UV opsin is expressed in each eye type and co-expressed with a visible light-sensitive opsin in ventral larval eyes.

    Science.gov (United States)

    Battelle, Barbara-Anne; Kempler, Karen E; Harrison, Alexandra; Dugger, Donald R; Payne, Richard

    2014-09-01

    The eyes of the horseshoe crab, Limulus polyphemus, are a model for studies of visual function and the visual systems of euarthropods. Much is known about the structure and function of L. polyphemus photoreceptors, much less about their photopigments. Three visible-light-sensitive L. polyphemus opsins were characterized previously (LpOps1, 2 and 5). Here we characterize a UV opsin (LpUVOps1) that is expressed in all three types of L. polyphemus eyes. It is expressed in most photoreceptors in median ocelli, the only L. polyphemus eyes in which UV sensitivity was previously detected, and in the dendrite of eccentric cells in lateral compound eyes. Therefore, eccentric cells, previously thought to be non-photosensitive second-order neurons, may actually be UV-sensitive photoreceptors. LpUVOps1 is also expressed in small photoreceptors in L. polyphemus ventral larval eyes, and intracellular recordings from these photoreceptors confirm that LpUVOps1 is an active, UV-sensitive photopigment. These photoreceptors also express LpOps5, which we demonstrate is an active, long-wavelength-sensitive photopigment. Thus small photoreceptors in ventral larval eyes, and probably those of the other larval eyes, have dual sensitivity to UV and visible light. Interestingly, the spectral tuning of small ventral photoreceptors may change day to night, because the level of LpOps5 in their rhabdoms is lower during the day than during the night, whereas LpUVOps1 levels show no diurnal change. These and previous findings show that opsin co-expression and the differential regulation of co-expressed opsins in rhabdoms is a common feature of L. polyphemus photoreceptors. © 2014. Published by The Company of Biologists Ltd.

  2. Meta-Analysis of Microarray Data of Rainbow Trout Fry Gonad Differentiation Modulated by Ethynylestradiol.

    Directory of Open Access Journals (Sweden)

    Sophie Depiereux

    Full Text Available Sex differentiation in fish is a highly labile process easily reversed by the use of exogenous hormonal treatment and has led to environmental concerns since low doses of estrogenic molecules can adversely impact fish reproduction. The goal of this study was to identify pathways altered by treatment with ethynylestradiol (EE2 in developing fish and to find new target genes to be tested further for their possible role in male-to-female sex transdifferentiation. To this end, we have successfully adapted a previously developed bioinformatics workflow to a meta-analysis of two datasets studying sex reversal following exposure to EE2 in juvenile rainbow trout. The meta-analysis consisted of retrieving the intersection of the top gene lists generated for both datasets, performed at different levels of stringency. The intersecting gene lists, enriched in true positive differentially expressed genes (DEGs, were subjected to over-representation analysis (ORA which allowed identifying several statistically significant enriched pathways altered by EE2 treatment and several new candidate pathways, such as progesterone-mediated oocyte maturation and PPAR signalling. Moreover, several relevant key genes potentially implicated in the early transdifferentiation process were selected. Altogether, the results show that EE2 has a great effect on gene expression in juvenile rainbow trout. The feminization process seems to result from the altered transcription of genes implicated in normal female gonad differentiation, resulting in expression similar to that observed in normal females (i.e. the repression of key testicular markers cyp17a1, cyp11b, tbx1, as well as from other genes (including transcription factors that respond specifically to the EE2 treatment. The results also showed that the bioinformatics workflow can be applied to different types of microarray platforms and could be generalized to (ecotoxicogenomics studies for environmental risk assessment

  3. An efficient co-expression and purification system for the complex of Stx4 and C-terminal domain of Synip

    International Nuclear Information System (INIS)

    Tian Wei; Ma Cong; Liu Yingfang; Xu Tao

    2008-01-01

    Synip and Stx4 complex plays a key role in GLUT4 vesicle trafficking and fusion with plasma membrane. The interaction of Synip with Stx4 prevents interaction of VAMP2 located in GLUT4 vesicle with Stx4 in basal state. Insulin induces the dissociation of the Synip and Stx4 complex, and then triggers VAMP2 to interact with Stx4 to form the SNARE complex, thus promoting the vesicle fusion. In this report, we adopt a novel system for co-expression of the Synip and Stx4 by using two common vectors pGEX6p-1 and pET28a(+) to investigate their expression, purification, and interaction. Through this co-expression system, we successfully co-expressed the Synip and Stx4 complex with high yield, and co-purified at an approximate 1:1 molar ratio with high purity (95%). We also demonstrate that the 1-28 residues of Stx4 are dispensable for interaction with Synip using this co-expression system

  4. Co-expression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

    Science.gov (United States)

    2012-09-01

    ovarian cancer stem cell markers to consider it as a new experimental target for novel nanotechnology approaches capable of destroying ovarian cancer stem...FSHR mRNA after several generations in an amount consistent with stem cell characteristics. Nude mouse experiments to confirm co-expression in vivoare

  5. Neurotensin Is Co-Expressed, Co-Released And Acts Together With Glp-1 And Pyy In Enteroendocrine Control Of Metabolism

    DEFF Research Database (Denmark)

    Grunddal, Kaare Villum; Ratner, Cecilia F; Svendsen, Berit

    2016-01-01

    increasingly multi-hormonal, i.e. co-expressing PYY and neurotensin as they move up the villus. Pro-glucagon promoter and pertussis toxin receptor driven cell ablation and reappearance studies indicated that although all the cells die, the GLP-1 cells reappear more quickly than PYY and neurotensin positive...

  6. Development of stable Vibrio cholerae O1 Hikojima type vaccine strains co-expressing the Inaba and Ogawa lipopolysaccharide antigens.

    Directory of Open Access Journals (Sweden)

    Stefan L Karlsson

    Full Text Available We describe here the development of stable classical and El Tor V. cholerae O1 strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of O1 lipopolysaccharide (LPS. Mutation of the wbeT gene reduced LPS perosamine methylation and thereby gave only partial transformation into Ogawa LPS on the cell surface. The strains express approximately equal amounts of Inaba- and Ogawa-LPS antigens which are preserved after formalin-inactivation of the bacteria. Oral immunizations of both inbred and outbred mice with formalin-inactivated whole-cell vaccine preparations of these strains elicited strong intestinal IgA anti-LPS as well as serum vibriocidal antibody responses against both Inaba and Ogawa that were fully comparable to the responses induced by the licensed Dukoral vaccine. Passive protection studies in infant mice showed that immune sera raised against either of the novel Hikojima vaccine strains protected baby mice against infection with virulent strains of both serotypes. This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.

  7. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  8. Co-expression of two subtypes of melatonin receptor on rat M1-type intrinsically photosensitive retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Wen-Long Sheng

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGCs are involved in circadian and other non-image forming visual responses. An open question is whether the activity of these neurons may also be under the regulation mediated by the neurohormone melatonin. In the present work, by double-staining immunohistochemical technique, we studied the expression of MT1 and MT2, two known subtypes of mammalian melatonin receptors, in rat ipRGCs. A single subset of retinal ganglion cells labeled by the specific antibody against melanopsin exhibited the morphology typical of M1-type ipRGCs. Immunoreactivity for both MT1 and MT2 receptors was clearly seen in the cytoplasm of all labeled ipRGCs, indicating that these two receptors were co-expressed in each of these neurons. Furthermore, labeling for both the receptors were found in neonatal M1 cells as early as the day of birth. It is therefore highly plausible that retinal melatonin may directly modulate the activity of ipRGCs, thus regulating non-image forming visual functions.

  9. Construction and identification of double-gene co-expression vector with radiation-inducible human TRAIL and endostatin

    International Nuclear Information System (INIS)

    Li Yanbo; Guo Caixia; Gong Pingsheng; Liu Yang; Liangshuo; Wang Hongfang; Wang Jianfeng; Gong Shouliang

    2010-01-01

    Objective: To construct a recombinant plasmid pshuttle-Egr1-shTRAIL-shES containing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin double genes. Methods: The secretary endostatin gene (shES) fragment was amplified from the pMD19T-endostatin vector by PCR. The shES gene was ligated to pMD19Tand sequenced. Finally, using the gene recombinant technique, the recombinant plasmid pshuttle-Egr1- shTRAIL-shES with radiation-inducible Egr1 promoter, secretary TRAIL and endostatin double-gene was constructed. Results: The sequence of the shES gene was in concordance with that anticipated indicating shES gene was acquired successfully.Moreover, the results acquired by PCR and restrictive digestion identification of the recombinant plasmid pshuttle-Egr1-shTRAIL-shES and all the vectors refered to its construction confirmed that pshuttle-Egr1-shTRAIL-shES was constructed correctly. Conclusion: The radiation-inducible double-gene co-expression vector pshuttle-Egr1-shTRAIL-shES is constructed successfully, which would set the experimental foundation for further study on the anti-tumor effect of TRAIL and endostatin double-gene-radiotherapy and its related mechanisms. (authors)

  10. Bifurcation analysis of a neutral delay differential equation modelling the torsional motion of a driven drill-string

    Energy Technology Data Exchange (ETDEWEB)

    Balanov, A.G.; Janson, N.B. E-mail: n.janson@lancaster.ac.uk; McClintock, P.V.E.; Tucker, R.W.; Wang, C.H.T

    2003-01-01

    Using techniques from dynamical systems analysis we explore numerically the solution space, under parametric variation, of a neutral differential delay equation that arises naturally in the Cosserat description of torsional waves on a driven drill-string.

  11. Bifurcation analysis of a neutral delay differential equation modelling the torsional motion of a driven drill-string

    International Nuclear Information System (INIS)

    Balanov, A.G.; Janson, N.B.; McClintock, P.V.E.; Tucker, R.W.; Wang, C.H.T.

    2003-01-01

    Using techniques from dynamical systems analysis we explore numerically the solution space, under parametric variation, of a neutral differential delay equation that arises naturally in the Cosserat description of torsional waves on a driven drill-string

  12. Recurrence rates following I-131 therapy of differentiated thyroid carcinoma: results of meta-analysis

    International Nuclear Information System (INIS)

    Obaldo, J.M.

    1990-01-01

    To examine the efficacy of I-131 therapy in decreasing recurrence rates after surgery for differentiated thyroid carcinoma, a research tool called meta-analysis was used. Data were pooled from five published studies which evaluated recurrences following at least sub-total thyroidectomy with or without I-131 ablation of remnants. Of 1332 patients managed surgically only 202 (15%) developed recurrences compared to 36 of 339 (11%) treated with radioiodine. This difference was statistically significant at p<.05. When a separate analysis of only those studies which directly compared the two modes of management was conducted, recurrence rates for patients treated by surgery alone was higher at 18% (185 of 1034) compared with those who had subsequent I-131 therapy with a rate of 9% (27 of 297). This difference was again significant at p <.001. This meta-analysis strongly suggests that the use of I-131 for ablation of post-surgical thyroid remnants significantly reduces recurrence rates in patients with differentiated thyroid carcinoma. (Auth.). 34 refs., 1 tab.; 1 fig

  13. Analysis of Nonlinear Duopoly Games with Product Differentiation: Stability, Global Dynamics, and Control

    Directory of Open Access Journals (Sweden)

    S. S. Askar

    2017-01-01

    Full Text Available Many researchers have used quadratic utility function to study its influences on economic games with product differentiation. Such games include Cournot, Bertrand, and a mixed-type game called Cournot-Bertrand. Within this paper, a cubic utility function that is derived from a constant elasticity of substitution production function (CES is introduced. This cubic function is more desirable than the quadratic one besides its amenability to efficiency analysis. Based on that utility a two-dimensional Cournot duopoly game with horizontal product differentiation is modeled using a discrete time scale. Two different types of games are studied in this paper. In the first game, firms are updating their output production using the traditional bounded rationality approach. In the second game, firms adopt Puu’s mechanism to update their productions. Puu’s mechanism does not require any information about the profit function; instead it needs both firms to know their production and their profits in the past time periods. In both scenarios, an explicit form for the Nash equilibrium point is obtained under certain conditions. The stability analysis of Nash point is considered. Furthermore, some numerical simulations are carried out to confirm the chaotic behavior of Nash equilibrium point. This analysis includes bifurcation, attractor, maximum Lyapunov exponent, and sensitivity to initial conditions.

  14. Differentiation of the aromas of Merlot and Cabernet Sauvignon wines using sensory and instrumental analysis.

    Science.gov (United States)

    Kotseridis, Y; Razungles, A; Bertrand, A; Baumes, R

    2000-11-01

    The aromas of six Merlot and three Cabernet Sauvignon wines of the 1996 vintage from the Bordeaux region were evaluated by sensory analysis. A panel of selected enology students was trained to assess 20 attributes previously generated for these wines by enologists of Bordeaux. Using statistical methods, this 20-attribute list was reduced to a 12-attribute list. The aroma profiles of the wines of Merlot and Cabernet Sauvignon were very close. Differentiation of the wines of these two varieties was significant only for the caramel descriptor, which was rated higher in the Merlot wines. Gas chromatography/olfactometry (GC/O) and GC/MS analyses were used to detect and identify the potent odorants with the caramel odor in the two most differentiated samples for this attribute, a Merlot wine and a Cabernet Sauvignon wine. Two odorant zones with this odor resulted in identification of 4-hydroxy-2,5-dimethylfuran-3(2H)-one (HDMF) and 4-hydroxy-2(or 5)-ethyl-5(or 2)-methylfuran-3(2H)-one (HEMF). Aroma extract dilution analysis (AEDA) method showed a higher dilution factor (FD) for HDMF in the Merlot wine extract than in the Cabernet Sauvignon extract. The HDMF levels determined in the wines studied using a stable isotope dilution assay (SIDA) method were consistent with the results found by sensory analysis and GC/O; i.e., higher HDMF levels were present in the Merlot wines than in the Cabernet Sauvignon wines.

  15. Accounting for technical noise in differential expression analysis of single-cell RNA sequencing data.

    Science.gov (United States)

    Jia, Cheng; Hu, Yu; Kelly, Derek; Kim, Junhyong; Li, Mingyao; Zhang, Nancy R

    2017-11-02

    Recent technological breakthroughs have made it possible to measure RNA expression at the single-cell level, thus paving the way for exploring expression heterogeneity among individual cells. Current single-cell RNA sequencing (scRNA-seq) protocols are complex and introduce technical biases that vary across cells, which can bias downstream analysis without proper adjustment. To account for cell-to-cell technical differences, we propose a statistical framework, TASC (Toolkit for Analysis of Single Cell RNA-seq), an empirical Bayes approach to reliably model the cell-specific dropout rates and amplification bias by use of external RNA spike-ins. TASC incorporates the technical parameters, which reflect cell-to-cell batch effects, into a hierarchical mixture model to estimate the biological variance of a gene and detect differentially expressed genes. More importantly, TASC is able to adjust for covariates to further eliminate confounding that may originate from cell size and cell cycle differences. In simulation and real scRNA-seq data, TASC achieves accurate Type I error control and displays competitive sensitivity and improved robustness to batch effects in differential expression analysis, compared to existing methods. TASC is programmed to be computationally efficient, taking advantage of multi-threaded parallelization. We believe that TASC will provide a robust platform for researchers to leverage the power of scRNA-seq. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Stability and bifurcation analysis of a generalized scalar delay differential equation.

    Science.gov (United States)

    Bhalekar, Sachin

    2016-08-01

    This paper deals with the stability and bifurcation analysis of a general form of equation D(α)x(t)=g(x(t),x(t-τ)) involving the derivative of order α ∈ (0, 1] and a constant delay τ ≥ 0. The stability of equilibrium points is presented in terms of the stability regions and critical surfaces. We provide a necessary condition to exist chaos in the system also. A wide range of delay differential equations involving a constant delay can be analyzed using the results proposed in this paper. The illustrative examples are provided to explain the theory.

  17. Chemometric investigations on the differentiated evaluation of element trace analysis in river waters

    International Nuclear Information System (INIS)

    Einax, J.; Geiss, S.

    1994-01-01

    The combination of sequential leaching methods for a first assessment of the kind of species in river sediments with multivariate-statistical methods (like factor analysis) for identifying anthropogenic and/or geogenic loading is useful for the differentiated characterization of the pollution state of a river. Electrochemical investigations, planned on the basis of statistical design and following empirical modelling, enables quantitative conclusions on the binding forms of heavy metals in river waters. Deposition-remobilisation effects of heavy metals in the complex system river water-river sediment can be described by PLS modelling. (orig.)

  18. DIFFERENTIAL ANALYSIS OF VOLUMETRIC STRAINS IN POROUS MATERIALS IN TERMS OF WATER FREEZING

    Directory of Open Access Journals (Sweden)

    Rusin Z.

    2013-06-01

    Full Text Available The paper presents the differential analysis of volumetric strain (DAVS. The method allows measurements of volumetric deformations of capillary-porous materials caused by water-ice phase change. The VSE indicator (volumetric strain effect, which under certain conditions can be interpreted as the minimum degree of phase change of water contained in the material pores, is proposed. The test results (DAVS for three materials with diversified microstructure: clinker brick, calcium-silicate brick and Portland cement mortar were compared with the test results for pore characteristics obtained with the mercury intrusion porosimetry.

  19. A resampling-based meta-analysis for detection of differential gene expression in breast cancer

    International Nuclear Information System (INIS)

    Gur-Dedeoglu, Bala; Konu, Ozlen; Kir, Serkan; Ozturk, Ahmet Rasit; Bozkurt, Betul; Ergul, Gulusan; Yulug, Isik G

    2008-01-01

    Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures. A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis. The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results. The

  20. A resampling-based meta-analysis for detection of differential gene expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Ergul Gulusan

    2008-12-01

    Full Text Available Abstract Background Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures. Methods A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC, and invasive lobular carcinoma (ILC samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis. Results The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively. The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real

  1. Differentiation of endosperm transfer cells of barley: a comprehensive analysis at the micro-scale.

    Science.gov (United States)

    Thiel, Johannes; Riewe, David; Rutten, Twan; Melzer, Michael; Friedel, Swetlana; Bollenbeck, Felix; Weschke, Winfriede; Weber, Hans

    2012-08-01

    Barley endosperm cells differentiate into transfer cells (ETCs) opposite the nucellar projection. To comprehensively analyse ETC differentiation, laser microdissection-based transcript and metabolite profiles were obtained from laser microdissected tissues and cell morphology was analysed. Flange-like secondary-wall ingrowths appeared between 5 and 7 days after pollination within the three outermost cell layers. Gene expression analysis indicated that ethylene-signalling pathways initiate ETC morphology. This is accompanied by gene activity related to cell shape control and vesicle transport, with abundant mitochondria and endomembrane structures. Gene expression analyses indicate predominant formation of hemicelluloses, glucuronoxylans and arabinoxylans, and transient formation of callose, together with proline and 4-hydroxyproline biosynthesis. Activation of the methylation cycle is probably required for biosynthesis of phospholipids, pectins and ethylene. Membrane microdomains involving sterols/sphingolipids and remorins are potentially involved in ETC development. The transcriptional activity of assimilate and micronutrient transporters suggests ETCs as the main uptake organs of solutes into the endosperm. Accordingly, the endosperm grows maximally after ETCs are fully developed. Up-regulated gene expression related to amino acid catabolism, C:N balances, carbohydrate oxidation, mitochondrial activity and starch degradation meets high demands for respiratory energy and carbohydrates, required for cell proliferation and wall synthesis. At 10 days after pollination, ETCs undergo further differentiation, potentially initiated by abscisic acid, and metabolism is reprogrammed as shown by activated storage and stress-related processes. Overall, the data provide a comprehensive view of barley ETC differentiation and development, and identify candidate genes and associated pathways. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  2. Differentiation of Xylella fastidiosa strains via multilocus sequence analysis of environmentally mediated genes (MLSA-E).

    Science.gov (United States)

    Parker, Jennifer K; Havird, Justin C; De La Fuente, Leonardo

    2012-03-01

    Isolates of the plant pathogen Xylella fastidiosa are genetically very similar, but studies on their biological traits have indicated differences in virulence and infection symptomatology. Taxonomic analyses have identified several subspecies, and phylogenetic analyses of housekeeping genes have shown broad host-based genetic differences; however, results are still inconclusive for genetic differentiation of isolates within subspecies. This study employs multilocus sequence analysis of environmentally mediated genes (MLSA-E; genes influenced by environmental factors) to investigate X. fastidiosa relationships and differentiate isolates with low genetic variability. Potential environmentally mediated genes, including host colonization and survival genes related to infection establishment, were identified a priori. The ratio of the rate of nonsynonymous substitutions to the rate of synonymous substitutions (dN/dS) was calculated to select genes that may be under increased positive selection compared to previously studied housekeeping genes. Nine genes were sequenced from 54 X. fastidiosa isolates infecting different host plants across the United States. Results of maximum likelihood (ML) and Bayesian phylogenetic (BP) analyses are in agreement with known X. fastidiosa subspecies clades but show novel within-subspecies differentiation, including geographic differentiation, and provide additional information regarding host-based isolate variation and specificity. dN/dS ratios of environmentally mediated genes, though gene dN/dS ratios and correlate with increased sequence variability. MLSA-E can more precisely resolve relationships between closely related bacterial strains with low genetic variability, such as X. fastidiosa isolates. Discovering the genetic relationships between X. fastidiosa isolates will provide new insights into the epidemiology of populations of X. fastidiosa, allowing improved disease management in economically important crops.

  3. A conventional PCR for differentiating common taeniid species of dogs based on in silico microsatellite analysis

    Directory of Open Access Journals (Sweden)

    Saeedeh Shamsaddini

    2017-09-01

    Full Text Available ABSTRACT Canine taeniids are among the major tapeworms with remarkable medical and economic significance. Reliable diagnosis and differentiation of dog taeniids using simple and sensitive tools are of paramount importance for establishing an efficient surveillance system. Microsatellites as abundant unique tandem repeats of short DNA motifs are useful genetic markers for molecular epidemiological studies. The purpose of the present study was to find a primer pair for rapid differentiation of major tapeworms of dogs, Taenia hydatigena, T. multiceps, T. ovis and Echinococcus granulosus, by screening existing nucleotide data. All the mitochondrial genome records as well as non-coding ITS1 sequences of Taeniidae species were downloaded from Nucleotide database from NCBI. For prediction and analysis of potential loci of STR/SSR in ITS1 as well as mitochondrial regions, we used ChloroMitoSSRDB 2.0 and GMATo v1.2. software. Different tapeworm species were categorized according to different motif sequences and type and size of each microsatellite locus. Three primer sets were designed and tested for differentiating taeniid species and evaluated in a conventional PCR system. Four taeniid species were successfully differentiated using a primer pair in a simple conventional PCR system. We predicted 2-19 and 1-4 microsatellite loci in ITS1 and mitochondrial genome, respectively. In ITS1, 41 Di and 21 Tri motifs were found in the taeniids while the majority of the motifs in the mitochondrial genome were Tetra (89 and Tri (70. It is documented that the number and diversity of microsatellite loci is higher in nuclear ITS1 region than mostly coding mitochondrial genome.

  4. Static and free vibration analysis of carbon nano wires based on Timoshenko beam theory using differential quadrature method

    Directory of Open Access Journals (Sweden)

    Maziar Janghorban

    Full Text Available Static and free vibration analysis of carbon nano wires with rectangular cross section based on Timoshenko beam theory is studied in this research. Differential quadrature method (DQM is employed to solve the governing equations. From the knowledge of author, it is the first time that free vibration of nano wires is investigated. It is also the first time that differential quadrature method is used for bending analysis of nano wires.

  5. Diagnostic Performance of Mammographic Texture Analysis in the Differential Diagnosis of Benign and Malignant Breast Tumors.

    Science.gov (United States)

    Li, Zhiming; Yu, Lan; Wang, Xin; Yu, Haiyang; Gao, Yuanxiang; Ren, Yande; Wang, Gang; Zhou, Xiaoming

    2017-11-09

    The purpose of this study was to investigate the diagnostic performance of mammographic texture analysis in the differential diagnosis of benign and malignant breast tumors. Digital mammography images were obtained from the Picture Archiving and Communication System at our institute. Texture features of mammographic images were calculated. Mann-Whitney U test was used to identify differences between the benign and malignant group. The receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of texture features. Significant differences of texture features of histogram, gray-level co-occurrence matrix (GLCM) and run length matrix (RLM) were found between the benign and malignant breast group (P  .05). The AUROCs of imaging-based diagnosis, texture analysis, and imaging-based diagnosis combined with texture analysis were 0.873, 0.863, and 0.961, respectively. When imaging-based diagnosis was combined with texture analysis, the AUROC was higher than that of imaging-based diagnosis or texture analysis (P benign and malignant breast tumors. Furthermore, the combination of imaging-based diagnosis and texture analysis can significantly improve diagnostic performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Divergent and convergent modes of interaction between wheat and Puccinia graminis f. sp. tritici isolates revealed by the comparative gene co-expression network and genome analyses.

    Science.gov (United States)

    Rutter, William B; Salcedo, Andres; Akhunova, Alina; He, Fei; Wang, Shichen; Liang, Hanquan; Bowden, Robert L; Akhunov, Eduard

    2017-04-12

    Two opposing evolutionary constraints exert pressure on plant pathogens: one to diversify virulence factors in order to evade plant defenses, and the other to retain virulence factors critical for maintaining a compatible interaction with the plant host. To better understand how the diversified arsenals of fungal genes promote interaction with the same compatible wheat line, we performed a comparative genomic analysis of two North American isolates of Puccinia graminis f. sp. tritici (Pgt). The patterns of inter-isolate divergence in the secreted candidate effector genes were compared with the levels of conservation and divergence of plant-pathogen gene co-expression networks (GCN) developed for each isolate. Comprative genomic analyses revealed substantial level of interisolate divergence in effector gene complement and sequence divergence. Gene Ontology (GO) analyses of the conserved and unique parts of the isolate-specific GCNs identified a number of conserved host pathways targeted by both isolates. Interestingly, the degree of inter-isolate sub-network conservation varied widely for the different host pathways and was positively associated with the proportion of conserved effector candidates associated with each sub-network. While different Pgt isolates tended to exploit similar wheat pathways for infection, the mode of plant-pathogen interaction varied for different pathways with some pathways being associated with the conserved set of effectors and others being linked with the diverged or isolate-specific effectors. Our data suggest that at the intra-species level pathogen populations likely maintain divergent sets of effectors capable of targeting the same plant host pathways. This functional redundancy may play an important role in the dynamic of the "arms-race" between host and pathogen serving as the basis for diverse virulence strategies and creating conditions where mutations in certain effector groups will not have a major effect on the pathogen

  7. Co-expression of TAL1 and ADH1 in recombinant xylose-fermenting Saccharomyces cerevisiae improves ethanol production from lignocellulosic hydrolysates in the presence of furfural.

    Science.gov (United States)

    Hasunuma, Tomohisa; Ismail, Ku Syahidah Ku; Nambu, Yumiko; Kondo, Akihiko

    2014-02-01

    Lignocellulosic biomass dedicated to bioethanol production usually contains pentoses and inhibitory compounds such as furfural that are not well tolerated by Saccharomyces cerevisiae. Thus, S. cerevisiae strains with the capability of utilizing both glucose and xylose in the presence of inhibitors such as furfural are very important in industrial ethanol production. Under the synergistic conditions of transaldolase (TAL) and alcohol dehydrogenase (ADH) overexpression, S. cerevisiae MT8-1X/TAL-ADH was able to produce 1.3-fold and 2.3-fold more ethanol in the presence of 70 mM furfural than a TAL-expressing strain and a control strain, respectively. We also tested the strains' ability by mimicking industrial ethanol production from hemicellulosic hydrolysate containing fermentation inhibitors, and ethanol production was further improved by 16% when using MT8-1X/TAL-ADH compared to the control strain. Transcript analysis further revealed that besides the pentose phosphate pathway genes TKL1 and TAL1, ADH7 was also upregulated in response to furfural stress, which resulted in higher ethanol production compared to the TAL-expressing strain. The improved capability of our modified strain was based on its capacity to more quickly reduce furfural in situ resulting in higher ethanol production. The co-expression of TAL/ADH genes is one crucial strategy to fully utilize undetoxified lignocellulosic hydrolysate, leading to cost-competitive ethanol production. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  8. Co-expression of Nisin Z and Leucocin C as a Basis for Effective Protection Against Listeria monocytogenes in Pasteurized Milk

    Directory of Open Access Journals (Sweden)

    Yuxin Fu

    2018-03-01

    Full Text Available Nisin, an important bacteriocin from Lactococcus lactis subsp., is primarily active against various Gram-positive bacteria. Leucocin C, produced by Leuconostoc carnosum 4010, is a class IIa bacteriocin used to inhibit the growth of Listeria monocytogenes. Because two bacteriocins have different modes of action, the combined use of them could be a potential strategy for effective inhibition of foodborne pathogens. In this study, L. lactis N8-r-lecCI (N8 harboring lecCI gene coexpressing nisin–leucocin C was constructed based on the food-grade carrier L. lactis N8. Production of both bacteriocins was stably maintained. Antimicrobial measurements showed that the recombinant strain is effectively against Listeria monocytogenes and Staphylococcus aureus and moderately against Salmonella enterica serovar Enteritidis and Escherichia coli because of its stronger antibacterial activity than the parental strain, this result first demonstrated that the co-expression of nisin and leucocin C results in highly efficient antimicrobial activity. The checkerboard assay showed that the antibacterial activity of L. lactis N8-r-lecCI supernatant was enhanced in the presence of low concentration of EDTA. Analysis of the scanning electron microscope image showed the biggest cellular morphology change in L. monocytogenes treated with a mixture of EDTA and L. lactis N8-r-lecCI supernatant. The practical effect was verified in pasteurized milk through time-kill assay. The L. lactis N8-r-lecCI strain expressing both nisin and leucocin C has a promising application prospect in pasteurized milk processing and preservation because of its strong antibacterial activity.

  9. Construction of a plasmid for co-expression of mouse membrane-bound form of IL-15 and RAE-1ε and its biological activity.

    Science.gov (United States)

    Qian, Li; Ji, Ming-Chun; Pan, Xin-Yuan; Gong, Wei-Juan; Tian, Fang; Duan, Qiu-Fang

    2011-05-01

    Interleukin 15 (IL-15) is a pivotal cytokine for the proliferation and activation of a specific group of immune cells such as natural killer (NK), IFN-producing killer dendritic cells (IKDC) and CD8 T cells. RAE-1ε, the ligand for the activating NKG2D receptor, which also play an important role in the proliferation and activation of NK cells and IKDCs. In this study, a membrane-bound form of IL-15 (termed mb15) encoding sequence and RAE-1ε gene were obtained by SOE-PCR or PCR amplification. The amplified mb15 and RAE-1ε gene were then digested and inserted into the multiple cloning site1 (MCS1) and MCS2 of pVITRO2-mcs vector, respectively. A recombinant eukaryotic expression vector for co-expression of mb15 and RAE-1ε was successfully constructed. After it was transfected to BaF3 cells, the expression of IL-15 and RAE-1ε in recombinant BaF3/mb15/RAE-1ε cells were verified by RT-PCR, western blot and FCM analysis. Furthermore, BaF3/mb15/RAE-1ε cells had the ability of promoting NK cells proliferation and IFN-γ secretion. In conclusion, BaF3/mb15/RAE-1ε cells were successfully constructed, which is very useful for further studies, especially for the expansion and activation of certain subsets of immune cells such as NK cells and IKDCs. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. The order of expression is a key factor in the production of active transglutaminase in Escherichia coli by co-expression with its pro-peptide

    Directory of Open Access Journals (Sweden)

    Liu Song

    2011-12-01

    Full Text Available Abstract Background Streptomyces transglutaminase (TGase is naturally synthesized as zymogen (pro-TGase, which is then processed to produce active enzyme by the removal of its N-terminal pro-peptide. This pro-peptide is found to be essential for overexpression of soluble TGase in E. coli. However, expression of pro-TGase by E. coli requires protease-mediated activation in vitro. In this study, we developed a novel co- expression method for the direct production of active TGase in E. coli. Results A TGase from S. hygroscopicus was expressed in E. coli only after fusing with the pelB signal peptide, but fusion with the signal peptide induced insoluble enzyme. Therefore, alternative protocol was designed by co-expressing the TGase and its pro-peptide as independent polypeptides under a single T7 promoter using vector pET-22b(+. Although the pro-peptide was co-expressed, the TGase fused without the signal peptide was undetectable in both soluble and insoluble fractions of the recombinant cells. Similarly, when both genes were expressed in the order of the TGase and the pro-peptide, the solubility of TGase fused with the signal peptide was not improved by the co-expression with its pro-peptide. Interestingly, active TGase was only produced by the cells in which the pro-peptide and the TGase were fused with the signal peptide and sequentially expressed. The purified recombinant and native TGase shared the similar catalytic properties. Conclusions Our results indicated that the pro-peptide can assist correct folding of the TGase inter-molecularly in E. coli, and expression of pro-peptide prior to that of TGase was essential for the production of active TGase. The co-expression strategy based on optimizing the order of gene expression could be useful for the expression of other functional proteins that are synthesized as a precursor.

  11. Methodological Choices in Muscle Synergy Analysis Impact Differentiation of Physiological Characteristics Following Stroke

    Directory of Open Access Journals (Sweden)

    Caitlin L. Banks

    2017-08-01

    Full Text Available Muscle synergy analysis (MSA is a mathematical technique that reduces the dimensionality of electromyographic (EMG data. Used increasingly in biomechanics research, MSA requires methodological choices at each stage of the analysis. Differences in methodological steps affect the overall outcome, making it difficult to compare results across studies. We applied MSA to EMG data collected from individuals post-stroke identified as either responders (RES or non-responders (nRES on the basis of a critical post-treatment increase in walking speed. Importantly, no clinical or functional indicators identified differences between the cohort of RES and nRES at baseline. For this exploratory study, we selected the five highest RES and five lowest nRES available from a larger sample. Our goal was to assess how the methodological choices made before, during, and after MSA affect the ability to differentiate two groups with intrinsic physiologic differences based on MSA results. We investigated 30 variations in MSA methodology to determine which choices allowed differentiation of RES from nRES at baseline. Trial-to-trial variability in time-independent synergy vectors (SVs and time-varying neural commands (NCs were measured as a function of: (1 number of synergies computed; (2 EMG normalization method before MSA; (3 whether SVs were held constant across trials or allowed to vary during MSA; and (4 synergy analysis output normalization method after MSA. MSA methodology had a strong effect on our ability to differentiate RES from nRES at baseline. Across all 10 individuals and MSA variations, two synergies were needed to reach an average of 90% variance accounted for (VAF. Based on effect sizes, differences in SV and NC variability between groups were greatest using two synergies with SVs that varied from trial-to-trial. Differences in SV variability were clearest using unit magnitude per trial EMG normalization, while NC variability was less sensitive to EMG

  12. Co-Expression analysis of miRNAs and target NBS-LRR genes in Cucumis sativus

    Science.gov (United States)

    Plants react against their biological enemies by activating the innate immune system. Their defense system comprises of various R-protein, which usually contain NBS-LRR domain. MicroRNAs (miRNAs) are important molecules of 2nd layer of plant defense and play pivotal role behind the scene. To support...

  13. Meta-Analysis on Blood Transcriptomic Studies Identifies Consistently Co-Expressed PPI Modules as Robust Markers of Human Ageing

    NARCIS (Netherlands)

    van den Akker, E.B.; Passtoors, W.M.; Jansen, R.; van Zwet, E.W.; Goeman, J.J.; Hulsman, M.; Emilsson, V.; Perola, M.; Willemsen, G.; Penninx, B.W.J.H.; Heijmans, B.T.; Maier, A.B.; Boomsma, D.I.; Kok, J.N.; Slagboom, P.E.; Reinders, M.J.T.; Beekman, M.

    2014-01-01

    Summary: The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an

  14. Combining SPECT and Quantitative EEG Analysis for the Automated Differential Diagnosis of Disorders with Amnestic Symptoms

    Directory of Open Access Journals (Sweden)

    Yvonne Höller

    2017-09-01

    Full Text Available Single photon emission computed tomography (SPECT and Electroencephalography (EEG have become established tools in routine diagnostics of dementia. We aimed to increase the diagnostic power by combining quantitative markers from SPECT and EEG for differential diagnosis of disorders with amnestic symptoms. We hypothesize that the combination of SPECT with measures of interaction (connectivity in the EEG yields higher diagnostic accuracy than the single modalities. We examined 39 patients with Alzheimer's dementia (AD, 69 patients with depressive cognitive impairment (DCI, 71 patients with amnestic mild cognitive impairment (aMCI, and 41 patients with amnestic subjective cognitive complaints (aSCC. We calculated 14 measures of interaction from a standard clinical EEG-recording and derived graph-theoretic network measures. From regional brain perfusion measured by 99mTc-hexamethyl-propylene-aminoxime (HMPAO-SPECT in 46 regions, we calculated relative cerebral perfusion in these patients. Patient groups were classified pairwise with a linear support vector machine. Classification was conducted separately for each biomarker, and then again for each EEG- biomarker combined with SPECT. Combination of SPECT with EEG-biomarkers outperformed single use of SPECT or EEG when classifying aSCC vs. AD (90%, aMCI vs. AD (70%, and AD vs. DCI (100%, while a selection of EEG measures performed best when classifying aSCC vs. aMCI (82% and aMCI vs. DCI (90%. Only the contrast between aSCC and DCI did not result in above-chance classification accuracy (60%. In general, accuracies were higher when measures of interaction (i.e., connectivity measures were applied directly than when graph-theoretical measures were derived. We suggest that quantitative analysis of EEG and machine-learning techniques can support differentiating AD, aMCI, aSCC, and DCC, especially when being combined with imaging methods such as SPECT. Quantitative analysis of EEG connectivity could become

  15. Analysis of diffusion-weighted MR in the differential diagnosis of benign and malignant breast lesions with Meta-analysis

    International Nuclear Information System (INIS)

    Chen Xin; Zhang Qiujuan; Zhao Xian; Bai Zhilan; Zhang Yili; Guo Youmin

    2008-01-01

    Objective: To evaluate the value of diffusion-weighted imaging (DWI) in the differential diagnosis of benign and malignant breast lesions with Meta-analysis. Methods: English and Chinese articles published from 1997 to 2007 were searched in Cochrane library, Pubmed, Ovid, Elsevier, Springer databases and Chinese National Knowledge Infrastructure (CNKI), and selected according to the criteria for diagnostic research recommended by Cochrane Method Group. The characteristics of selected articles including the study background, design, results and diagnostic indicators were analyzed. Statistical analysis was performed with Meta-test version 0.9. Results: Six articles were included with a total of 479 lesions. The sensitivity and specificity of DWI for breast lesions ranged from 64.0% to 92.8% and from 45.8% to 96.7% respectively. All groups had homogeneity, and a fixation effects regression was developed. The pooled weighted sensitivity and specificity with 95% CI and Az was 86% (76%-92%), 80% (61%-91%) and 92.19% respectively. Sensitivity analysis demonstrated no remarkable change on heterogeneity. Conclusion: The value of ADC in DWI can help to differentiate the benign breast lesions from the malignant with good sensitivity and specificity. The further study is needed to assess the clinical application of the b-value and diagnostic threshold. (authors)

  16. Non-invasive differentiation of pancreatic lesions: is analysis of FDG kinetics superior to semiquantitative uptake value analysis?

    International Nuclear Information System (INIS)

    Nitzsche, E.U.; Hoegerle, S.; Mix, M.; Brink, I.; Otte, A.; Moser, E.

    2002-01-01

    The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomography (FDG PET) for the non-invasive differentiation of focal pancreatic lesions originating from cancer or chronic pancreatitis by combined visual image interpretation and semiquantitative uptake value analysis has been documented. However, in clinical routine some misdiagnosis is still observed. This is because there is potential overlap between the semiquantitative uptake values obtained for active inflammatory lesions and cancer. Therefore, this prospective study was undertaken to test the hypothesis that analysis of dynamic kinetics of focal pancreatic lesions based on FDG PET may more accurately determine the benign or malignant nature of such lesions. Thirty patients (56±17 years) were studied dynamically with FDG PET for a period of 60-90 min. Patients were assigned to one of four groups: control, acute pancreatitis, chronic pancreatitis or pancreatic cancer. Two observers, blinded to the clinical data, analysed the time-activity curves of FDG kinetics based on region of interest analysis. The diagnosis predicted by FDG PET was compared with the result of histological examination of the surgical specimen. Analysis of FDG kinetics revealed significant differences in the shape of the time-activity curve for controls, pancreatic cancer and inflammatory disease. Surprisingly, there was no significant difference in the time-activity curve shape for chronic pancreatitis and acute pancreatitis; this is, however, not a clinical issue. Furthermore, acquisition time (60 min vs 90 min) did not affect interpretation of the time-activity curve, so that scanning time may be regularly shortened to 60 min. Interobserver agreement was 1. Based on these findings, non-invasive differentiation between pancreatic cancer and chronic pancreatitis was correctly predicted in all cases, as confirmed by histology. In addition, the specificity was increased compared with that obtained from standardised

  17. Modeling Differentiation of Cognitive Abilities within the Higher-Order Factor Model Using Moderated Factor Analysis

    Science.gov (United States)

    Molenaar, Dylan; Dolan, Conor V.; Wicherts, Jelte M.; van der Maas, Han L. J.

    2010-01-01

    The general differentiation hypothesis states that the strength of the correlations among a set of IQ subtests varies with a given variable. Instances of the general differentiation hypothesis that have been considered in the literature include age and ability differentiation. Traditionally, the differentiation effect is attributed to the varying…

  18. Differential Bees Flux Balance Analysis with OptKnock for in silico microbial strains optimization.

    Directory of Open Access Journals (Sweden)

    Yee Wen Choon

    Full Text Available Microbial strains optimization for the overproduction of desired phenotype has been a popular topic in recent years. The strains can be optimized through several techniques in the field of genetic engineering. Gene knockout is a genetic engineering technique that can engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, the complexities of the metabolic networks have made the process to identify the effects of genetic modification on the desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to the combinatorial problem in obtaining optimal gene deletion strategy. Basically, the size of a genome-scale metabolic model is usually large. As the size of the problem increases, the computation time increases exponentially. In this paper, we propose Differential Bees Flux Balance Analysis (DBFBA with OptKnock to identify optimal gene knockout strategies for maximizing the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by improving the performance of a hybrid of Bees Algorithm and Flux Balance Analysis (BAFBA by hybridizing Differential Evolution (DE algorithm into neighborhood searching strategy of BAFBA. In addition, DBFBA is integrated with OptKnock to validate the results for improving the reliability the work. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as the model organisms, DBFBA has shown a better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes compared to the methods used in previous works.

  19. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method.

    Directory of Open Access Journals (Sweden)

    Ganglong Yang

    Full Text Available The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia, KK47 (low grade nonmuscle invasive bladder cancer, NMIBC, and YTS1 (metastatic bladder cancer have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.

  20. Differential analysis of contraction of the cardiac chambers by digital subtraction angiography

    International Nuclear Information System (INIS)

    Christ, F.; Nitsch, J.; Franken, T.; Manz, M.; Becher, H.; Bonn Univ.

    1986-01-01

    One hundred and thirty-six patients with various cardiac abnormalities that had been diagnosed by standard methods, were examined by I-V DSA; images of the left and right ventricles during a representative cardiac cycle were submitted to amplitude and phase analysis, using a Fourier transformation. Temporal differentiation of ventricular function was derived from the best available right anterior oblique projection; the amplitude of cardiac movement of abnormal areas in the myocardium were obtained from a grey scale or colour coding at a fixed point. Comparison with a control group of 35 individuals showed the following pathological findings: hypokinetic segments (33 cases) showed delay, dyskinesias (20 cases) showed complete separation of maximal phases, frequently with a double peak in the phase histogram; disturbances of cardiac rhythm (14 cases) showed atypical localisation of initiation of contraction: in Wolfe-Parkinson-White syndrome this is basal-anterior, in left bundle branch block and VVI stimulation it is apical inferior; in hypertrophic obstructive cardiomyopathy (eight cases) it is postero-basal inferior with high, narrow peaks on the phase histogram. Differential phase analysis on I-V DSA enables one to define cardiac contraction in a simple manner. (orig.) [de

  1. Quantitative Analysis of Signaling Networks across Differentially Embedded Tumors Highlights Interpatient Heterogeneity in Human Glioblastoma

    Science.gov (United States)

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen. PMID:24927040

  2. Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer.

    Science.gov (United States)

    Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

    2015-06-01

    To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

    Directory of Open Access Journals (Sweden)

    Xiaoke Ma

    2015-06-01

    Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

  4. Nonintrusive Polynomial Chaos Expansions for Sensitivity Analysis in Stochastic Differential Equations

    KAUST Repository

    Jimenez, M. Navarro; Le Maî tre, O. P.; Knio, Omar

    2017-01-01

    A Galerkin polynomial chaos (PC) method was recently proposed to perform variance decomposition and sensitivity analysis in stochastic differential equations (SDEs), driven by Wiener noise and involving uncertain parameters. The present paper extends the PC method to nonintrusive approaches enabling its application to more complex systems hardly amenable to stochastic Galerkin projection methods. We also discuss parallel implementations and the variance decomposition of the derived quantity of interest within the framework of nonintrusive approaches. In particular, a novel hybrid PC-sampling-based strategy is proposed in the case of nonsmooth quantities of interest (QoIs) but smooth SDE solution. Numerical examples are provided that illustrate the decomposition of the variance of QoIs into contributions arising from the uncertain parameters, the inherent stochastic forcing, and joint effects. The simulations are also used to support a brief analysis of the computational complexity of the method, providing insight on the types of problems that would benefit from the present developments.

  5. Melting temperature and enthalpy variations of phase change materials (PCMs): a differential scanning calorimetry (DSC) analysis

    Science.gov (United States)

    Sun, Xiaoqin; Lee, Kyoung Ok; Medina, Mario A.; Chu, Youhong; Li, Chuanchang

    2018-06-01

    Differential scanning calorimetry (DSC) analysis is a standard thermal analysis technique used to determine the phase transition temperature, enthalpy, heat of fusion, specific heat and activation energy of phase change materials (PCMs). To determine the appropriate heating rate and sample mass, various DSC measurements were carried out using two kinds of PCMs, namely N-octadecane paraffin and calcium chloride hexahydrate. The variations in phase transition temperature, enthalpy, heat of fusion, specific heat and activation energy were observed within applicable heating rates and sample masses. It was found that the phase transition temperature range increased with increasing heating rate and sample mass; while the heat of fusion varied without any established pattern. The specific heat decreased with the increase of heating rate and sample mass. For accuracy purpose, it is recommended that for PCMs with high thermal conductivity (e.g. hydrated salt) the focus will be on heating rate rather than sample mass.

  6. Product differentiation by analysis of DNA melting curves during the polymerase chain reaction.

    Science.gov (United States)

    Ririe, K M; Rasmussen, R P; Wittwer, C T

    1997-02-15

    A microvolume fluorometer integrated with a thermal cycler was used to acquire DNA melting curves during polymerase chain reaction by fluorescence monitoring of the double-stranded DNA specific dye SYBR Green I. Plotting fluorescence as a function of temperature as the thermal cycler heats through the dissociation temperature of the product gives a DNA melting curve. The shape and position of this DNA melting curve are functions of the GC/AT ratio, length, and sequence and can be used to differentiate amplification products separated by less than 2 degrees C in melting temperature. Desired products can be distinguished from undesirable products, in many cases eliminating the need for gel electrophoresis. Analysis of melting curves can extend the dynamic range of initial template quantification when amplification is monitored with double-stranded DNA specific dyes. Complete amplification and analysis of products can be performed in less than 15 min.

  7. Nonintrusive Polynomial Chaos Expansions for Sensitivity Analysis in Stochastic Differential Equations

    KAUST Repository

    Jimenez, M. Navarro

    2017-04-18

    A Galerkin polynomial chaos (PC) method was recently proposed to perform variance decomposition and sensitivity analysis in stochastic differential equations (SDEs), driven by Wiener noise and involving uncertain parameters. The present paper extends the PC method to nonintrusive approaches enabling its application to more complex systems hardly amenable to stochastic Galerkin projection methods. We also discuss parallel implementations and the variance decomposition of the derived quantity of interest within the framework of nonintrusive approaches. In particular, a novel hybrid PC-sampling-based strategy is proposed in the case of nonsmooth quantities of interest (QoIs) but smooth SDE solution. Numerical examples are provided that illustrate the decomposition of the variance of QoIs into contributions arising from the uncertain parameters, the inherent stochastic forcing, and joint effects. The simulations are also used to support a brief analysis of the computational complexity of the method, providing insight on the types of problems that would benefit from the present developments.

  8. Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal.

    Science.gov (United States)

    Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

    2015-05-18

    A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transformation. Cbx3 is up-regulated during gonad reversal and is likely to have a role in spermatogenesis. Rab37 is down-regulated during the reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked up in a protein network. These datasets in gonadal proteomes provide a new resource for further studies in gonadal development.

  9. An Analysis on a Dynamic Amplifier and Calibration Methods for a Pseudo-Differential Dynamic Comparator

    Science.gov (United States)

    Paik, Daehwa; Miyahara, Masaya; Matsuzawa, Akira

    This paper analyzes a pseudo-differential dynamic comparator with a dynamic pre-amplifier. The transient gain of a dynamic pre-amplifier is derived and applied to equations of the thermal noise and the regeneration time of a comparator. This analysis enhances understanding of the roles of transistor's parameters in pre-amplifier's gain. Based on the calculated gain, two calibration methods are also analyzed. One is calibration of a load capacitance and the other is calibration of a bypass current. The analysis helps designers' estimation for the accuracy of calibration, dead-zone of a comparator with a calibration circuit, and the influence of PVT variation. The analyzed comparator uses 90-nm CMOS technology as an example and each estimation is compared with simulation results.

  10. Semiparametric mixed-effects analysis of PK/PD models using differential equations.

    Science.gov (United States)

    Wang, Yi; Eskridge, Kent M; Zhang, Shunpu

    2008-08-01

    Motivated by the use of semiparametric nonlinear mixed-effects modeling on longitudinal data, we develop a new semiparametric modeling approach to address potential structural model misspecification for population pharmacokinetic/pharmacodynamic (PK/PD) analysis. Specifically, we use a set of ordinary differential equations (ODEs) with form dx/dt = A(t)x + B(t) where B(t) is a nonparametric function that is estimated using penalized splines. The inclusion of a nonparametric function in the ODEs makes identification of structural model misspecification feasible by quantifying the model uncertainty and provides flexibility for accommodating possible structural model deficiencies. The resulting model will be implemented in a nonlinear mixed-effects modeling setup for population analysis. We illustrate the method with an application to cefamandole data and evaluate its performance through simulations.

  11. ANALYSIS OF RELAPSE RATE AND METASTASES OF HIGH DIFFERENTIATED THYROID CANCER

    Directory of Open Access Journals (Sweden)

    E. V. Savenok

    2015-01-01

    Full Text Available  Analysis of rate of relapses and metastases with well-differentiated thyroid cancer was performed for patients in 2009 to 2013. The study involved 189 patients with thyroid cancer including 98 (51.9 % patients suffering from papillary thyroid cancer, 77 (40.7 % patients suffering from follicular thyroid cancer, and 14 (7.4 % patients suffering from medullary thyroid cancer. 2.04 % of the 98 patients suffering from papillary thyroid cancer manifested a relapse, and lymphogenic metastases of cancer were revealed with 1.0 % of patients. With follicular thyroid cancer (n = 77, lymphogenic metastases were registered in 7.8 % of cases, relapses were revealed in 1.3 % of cases. This analysis demonstrated that observation of patients for 5 years revealed a higher percentage of metastases with patients that suffered from follicular thyroid cancer.

  12. Identification of transcript regulatory patterns in cell differentiation.

    Science.gov (United States)

    Gusnanto, Arief; Gosling, John Paul; Pope, Christopher

    2017-10-15

    Studying transcript regulatory patterns in cell differentiation is critical in understanding its complex nature of the formation and function of different cell types. This is done usually by measuring gene expression at different stages of the cell differentiation. However, if the gene expression data available are only from the mature cells, we have some challenges in identifying transcript regulatory patterns that govern the cell differentiation. We propose to exploit the information of the lineage of cell differentiation in terms of correlation structure between cell types. We assume that two different cell types that are close in the lineage will exhibit many common genes that are co-expressed relative to those that are far in the lineage. Current analysis methods tend to ignore this correlation by testing for differential expression assuming some sort of independence between cell types. We employ a Bayesian approach to estimate the posterior distribution of the mean of expression in each cell type, by taking into account the cell formation path in the lineage. This enables us to infer genes that are specific in each cell type, indicating the genes are involved in directing the cell differentiation to that particular cell type. We illustrate the method using gene expression data from a study of haematopoiesis. R codes to perform the analysis are available in http://www1.maths.leeds.ac.uk/∼arief/R/CellDiff/. a.gusnanto@leeds.ac.uk. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  13. G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes

    Directory of Open Access Journals (Sweden)

    Lemay Danielle G

    2012-09-01

    Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The

  14. Predicting protein-protein interactions in Arabidopsis thaliana through integration of orthology, gene ontology and co-expression

    Directory of Open Access Journals (Sweden)

    Vandepoele Klaas

    2009-06-01

    Full Text Available Abstract Background Large-scale identification of the interrelationships between different components of the cell, such as the interactions between proteins, has recently gained great interest. However, unraveling large-scale protein-protein interaction maps is laborious and expensive. Moreover, assessing the reliability of the interactions can be cumbersome. Results In this study, we have developed a computational method that exploits the existing knowledge on protein-protein interactions in diverse species through orthologous relations on the one hand, and functional association data on the other hand to predict and filter protein-protein interactions in Arabidopsis thaliana. A highly reliable set of protein-protein interactions is predicted through this integrative approach making use of existing protein-protein interaction data from yeast, human, C. elegans and D. melanogaster. Localization, biological process, and co-expression data are used as powerful indicators for protein-protein interactions. The functional repertoire of the identified interactome reveals interactions between proteins functioning in well-conserved as well as plant-specific biological processes. We observe that although common mechanisms (e.g. actin polymerization and components (e.g. ARPs, actin-related proteins exist between different lineages, they are active in specific processes such as growth, cancer metastasis and trichome development in yeast, human and Arabidopsis, respectively. Conclusion We conclude that the integration of orthology with functional association data is adequate to predict protein-protein interactions. Through this approach, a high number of novel protein-protein interactions with diverse biological roles is discovered. Overall, we have predicted a reliable set of protein-protein interactions suitable for further computational as well as experimental analyses.

  15. Differential Expression and Functional Analysis of High-Throughput -Omics Data Using Open Source Tools.

    Science.gov (United States)

    Kebschull, Moritz; Fittler, Melanie Julia; Demmer, Ryan T; Papapanou, Panos N

    2017-01-01

    Today, -omics analyses, including the systematic cataloging of messenger RNA and microRNA sequences or DNA methylation patterns in a cell population, organ, or tissue sample, allow for an unbiased, comprehensive genome-level analysis of complex diseases, offering a large advantage over earlier "candidate" gene or pathway analyses. A primary goal in the analysis of these high-throughput assays is the detection of those features among several thousand that differ between different groups of samples. In the context of oral biology, our group has successfully utilized -omics technology to identify key molecules and pathways in different diagnostic entities of periodontal disease.A major issue when inferring biological information from high-throughput -omics studies is the fact that the sheer volume of high-dimensional data generated by contemporary technology is not appropriately analyzed using common statistical methods employed in the biomedical sciences.In this chapter, we outline a robust and well-accepted bioinformatics workflow for the initial analysis of -omics data generated using microarrays or next-generation sequencing technology using open-source tools. Starting with quality control measures and necessary preprocessing steps for data originating from different -omics technologies, we next outline a differential expression analysis pipeline that can be used for data from both microarray and sequencing experiments, and offers the possibility to account for random or fixed effects. Finally, we present an overview of the possibilities for a functional analysis of the obtained data.

  16. ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

    Science.gov (United States)

    Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

    2017-04-01

    To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

  17. FDG uptake heterogeneity evaluated by fractal analysis improves the differential diagnosis of pulmonary nodules

    Energy Technology Data Exchange (ETDEWEB)

    Miwa, Kenta, E-mail: kenta5710@gmail.com [Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Division of Medical Quantum Science, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inubushi, Masayuki, E-mail: inubushi@med.kawasaki-m.ac.jp [Department of Nuclear Medicine, Kawasaki Medical School, 577 Matsushima Kurashiki, Okayama 701-0192 (Japan); Wagatsuma, Kei, E-mail: kei1192@hotmail.co.jp [Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nagao, Michinobu, E-mail: minagao@radiol.med.kyushu-u.ac.jp [Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Murata, Taisuke, E-mail: taisuke113@gmail.com [Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Koyama, Masamichi, E-mail: masamichi.koyama@jfcr.or.jp [Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Koizumi, Mitsuru, E-mail: mitsuru@jfcr.or.jp [Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Sasaki, Masayuki, E-mail: msasaki@hs.med.kyushu-u.ac.jp [Division of Medical Quantum Science, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2014-04-15

    Purpose: The present study aimed to determine whether fractal analysis of morphological complexity and intratumoral heterogeneity of FDG uptake can help to differentiate malignant from benign pulmonary nodules. Materials and methods: We retrospectively analyzed data from 54 patients with suspected non-small cell lung cancer (NSCLC) who were examined by FDG PET/CT. Pathological assessments of biopsy specimens confirmed 35 and 19 nodules as NSCLC and inflammatory lesions, respectively. The morphological fractal dimension (m-FD), maximum standardized uptake value (SUV{sub max}) and density fractal dimension (d-FD) of target nodules were calculated from CT and PET images. Fractal dimension is a quantitative index of morphological complexity and tracer uptake heterogeneity; higher values indicate increased complexity and heterogeneity. Results: The m-FD, SUV{sub max} and d-FD significantly differed between malignant and benign pulmonary nodules (p < 0.05). Although the diagnostic ability was better for d-FD than m-FD and SUV{sub max}, the difference did not reach statistical significance. Tumor size correlated significantly with SUV{sub max} (r = 0.51, p < 0.05), but not with either m-FD or d-FD. Furthermore, m-FD combined with either SUV{sub max} or d-FD improved diagnostic accuracy to 92.6% and 94.4%, respectively. Conclusion: The d-FD of intratumoral heterogeneity of FDG uptake can help to differentially diagnose malignant and benign pulmonary nodules. The SUV{sub max} and d-FD obtained from FDG-PET images provide different types of information that are equally useful for differential diagnoses. Furthermore, the morphological complexity determined by CT combined with heterogeneous FDG uptake determined by PET improved diagnostic accuracy.

  18. Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis.

    Science.gov (United States)

    Kim, Hae Young; Park, Ji Hoon; Lee, Yoon Jin; Lee, Sung Soo; Jeon, Jong-June; Lee, Kyoung Ho

    2018-04-01

    Purpose To perform a systematic review and meta-analysis to identify computed tomographic (CT) features for differentiating complicated appendicitis in patients suspected of having appendicitis and to summarize their diagnostic accuracy. Materials and Methods Studies on diagnostic accuracy of CT features for differentiating complicated appendicitis (perforated or gangrenous appendicitis) in patients suspected of having appendicitis were searched in Ovid-MEDLINE, EMBASE, and the Cochrane Library. Overlapping descriptors used in different studies to denote the same image finding were subsumed under a single CT feature. Pooled diagnostic accuracy of the CT features was calculated by using a bivariate random effects model. CT features with pooled diagnostic odds ratios with 95% confidence intervals not including 1 were considered as informative. Results Twenty-three studies were included, and 184 overlapping descriptors for various CT findings were subsumed under 14 features. Of these, 10 features were informative for complicated appendicitis. There was a general tendency for these features to show relatively high specificity but low sensitivity. Extraluminal appendicolith, abscess, appendiceal wall enhancement defect, extraluminal air, ileus, periappendiceal fluid collection, ascites, intraluminal air, and intraluminal appendicolith showed pooled specificity greater than 70% (range, 74%-100%), but sensitivity was limited (range, 14%-59%). Periappendiceal fat stranding was the only feature that showed high sensitivity (94%; 95% confidence interval: 86%, 98%) but low specificity (40%; 95% confidence interval, 23%, 60%). Conclusion Ten informative CT features for differentiating complicated appendicitis were identified in this study, nine of which showed high specificity, but low sensitivity. © RSNA, 2017 Online supplemental material is available for this article.

  19. A real time analysis of the self-assembly process using thermal analysis inside the differential scanning calorimeter instrument.

    Science.gov (United States)

    Roy, Debmalya; Shastri, Babita; Mukhopadhyay, K

    2012-07-12

    The supramolecular assembly of the regioregular poly-3-hexylthiophene (rr-P3HT) in solution has been investigated thoroughly in the past. In the current study, our focus is on the enthalpy of nanofiber formation using thermal analysis techniques by performing the self-assembly process inside the differential scanning calorimetry (DSC) instrument. Thermogravimetric analysis (TGA) was carried out to check the concentration of the solvent during the self-assembly process of P3HT in p-xylene. Ultraviolet visible (UV-vis) spectophotometric technique, small-angle X-ray scattering (SAXS) experiment, atomic force microscopic (AFM), and scanning electron microscopic (SEM) images were used to characterize the different experimental yields generated by cooling the reaction mixture at desired temperatures. Comparison of the morphologies of self-assembled products at different fiber formation temperatures gives us an idea about the possible crystallization parameters which could affect the P3HT nanofiber morphology.

  20. Super-delta: a new differential gene expression analysis procedure with robust data normalization.

    Science.gov (United States)

    Liu, Yuhang; Zhang, Jinfeng; Qiu, Xing

    2017-12-21

    Normalization is an important data preparation step in gene expression analyses, designed to remove various systematic noise. Sample variance is greatly reduced after normalization, hence the power of subsequent statistical analyses is likely to increase. On the other hand, variance reduction is made possible by borrowing information across all genes, including differentially expressed genes (DEGs) and outliers, which will inevitably introduce some bias. This bias typically inflates type I error; and can reduce statistical power in certain situations. In this study we propose a new differential expression analysis pipeline, dubbed as super-delta, that consists of a multivariate extension of the global normalization and a modified t-test. A robust procedure is designed to minimize the bias introduced by DEGs in the normalization step. The modified t-test is derived based on asymptotic theory for hypothesis testing that suitably pairs with the proposed robust normalization. We first compared super-delta with four commonly used normalization methods: global, median-IQR, quantile, and cyclic loess normalization in simulation studies. Super-delta was shown to have better statistical power with tighter control of type I error rate than its competitors. In many cases, the performance of super-delta is close to that of an oracle test in which datasets without technical noise were used. We then applied all methods to a collection of gene expression datasets on breast cancer patients who received neoadjuvant chemotherapy. While there is a substantial overlap of the DEGs identified by all of them, super-delta were able to identify comparatively more DEGs than its competitors. Downstream gene set enrichment analysis confirmed that all these methods selected largely consistent pathways. Detailed investigations on the relatively small differences showed that pathways identified by super-delta have better connections to breast cancer than other methods. As a new pipeline, super

  1. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K.C.; Qiu, Jian-Wen

    2017-01-01

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

  2. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei

    2017-11-06

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

  3. Molecular polymorphism as a tool for differentiating ground beetles (Carabus species): application of ubiquitin PCR/SSCP analysis.

    Science.gov (United States)

    Boge, A; Gerstmeier, R; Einspanier, R

    1994-11-01

    Differentiation between Carabus species (ground beetle) and subspecies is difficult, although there have been extensive studies. To address this problem we have applied PCR in combination with SSCP analysis focussing on the evolutionally conservative ubiquitin gene to elaborate a new approach to molecular differentiation between species. We report that Carabidae possess an ubiquitin gene and that its gene has a multimeric structure. Differential SSCP analysis was performed with the monomeric form of the gene to generate a clear SSCP pattern. Such PCR/SSCP resulted in reproducible patterns throughout our experiments. Comparing different Carabus species (Carabus granulatus, C. irregularis, C. violaceus and C. auronitens) we could observe clear interspecies differences but no differences between genders. Some species showed some remarkable differences between the individuals. We suggest that the ubiquitin PCR-SSCP technique might be an additional tool for the differentiation of ground beetles.

  4. Enhanced performance for differential detection in coherent Brillouin optical time-domain analysis sensors

    Science.gov (United States)

    Shao, Liyang; Zhang, Yunpeng; Li, Zonglei; Zhang, Zhiyong; Zou, Xihua; Luo, Bin; Pan, Wei; Yan, Lianshan

    2016-11-01

    Logarithmic detectors (LogDs) have been used in coherent Brillouin optical time-domain analysis (BOTDA) sensors to reduce the effect of phase fluctuation, demodulation complexities, and measurement time. However, because of the inherent properties of LogDs, a DC component at the level of hundreds of millivolts that prohibits high-gain signal amplification (SA) could be generated, resulting in unacceptable data acquisition (DAQ) inaccuracies and decoding errors in the process of prototype integration. By generating a reference light at a level similar to the probe light, differential detection can be applied to remove the DC component automatically using a differential amplifier before the DAQ process. Therefore, high-gain SA can be employed to reduce quantization errors. The signal-to-noise ratio of the weak Brillouin gain signal is improved from ˜11.5 to ˜21.8 dB. A BOTDA prototype is implemented based on the proposed scheme. The experimental results show that the measurement accuracy of the Brillouin frequency shift (BFS) is improved from ±1.9 to ±0.8 MHz at the end of a 40-km sensing fiber.

  5. Analysis and differentiation of mineral dust by single particle laser mass spectrometry

    International Nuclear Information System (INIS)

    Gallavardin, S. J.; Lohmann, U.; Cziczo, Daniel J.

    2008-01-01

    This study evaluates the potential of single particle laser desorption/ionization mass spectrometry for the analysis of atmospherically relevant mineral dusts. Samples of hematite, goethite, calcium carbonate, calcium sulfate, silica, quartz, montmorrillonite, kaolinite, illite, hectorite, wollastonite and nephelinsyenit were investigated in positive and negative ion mode with a monopolar time-of-flight mass spectrometer where the desorption/ionization step was performed with a 193 nm excimer laser (∼10 9 W/cm 2 ). Particle size ranged from 500 nm to 3 (micro)m. Positive mass spectra mainly provide elemental composition whereas negative ion spectra provide information on element speciation and of a structural nature. The iron oxide, calcium-rich and aluminosilicate nature of particles is established in positive ion mode. The differentiation of calcium materials strongly relies on the calcium counter-ions in negative mass spectra. Aluminosilicates can be differentiated in both positive and negative ion mode using the relative abundance of various aluminum and silicon ions

  6. Differentiation between benign and malignant palatal tumors using conventional MRI: a retrospective analysis of 130 cases.

    Science.gov (United States)

    Zheng, Yingyan; Xiao, Zebin; Zhang, Hua; She, Dejun; Lin, Xuehua; Lin, Yu; Cao, Dairong

    2018-04-01

    To evaluate the discriminative value of conventional magnetic resonance imaging between benign and malignant palatal tumors. Conventional magnetic resonance imaging features of 130 patients with palatal tumors confirmed by histopathologic examination were retrospectively reviewed. Clinical data and imaging findings were assessed between benign and malignant tumors and between benign and low-grade malignant salivary gland tumors. The variables that were significant in differentiating benign from malignant lesions were further identified using logistic regression analysis. Moreover, imaging features of each common palatal histologic entity were statistically analyzed with the rest of the tumors to define their typical imaging features. Older age, partially defined and ill-defined margins, and absence of a capsule were highly suggestive of malignant palatal tumors, especially ill-defined margins (β = 6.400). The precision in determining malignant palatal tumors achieved a sensitivity of 92.8% and a specificity of 85.6%. In addition, irregular shape, ill-defined margins, lack of a capsule, perineural spread, and invasion of surrounding structures were more often associated with low-grade malignant salivary gland tumors. Conventional magnetic resonance imaging is useful for differentiating benign from malignant palatal tumors as well as benign salivary gland tumors from low-grade salivary gland malignancies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Analysis of differentially expressed proteins in Yersinia enterocolitica-infected HeLa cells.

    Science.gov (United States)

    Alugubelly, Navatha; Hercik, Kamil; Kibler, Peter; Nanduri, Bindu; Edelmann, Mariola J

    2016-05-01

    Yersinia enterocolitica is a facultative intracellular pathogen and a causative agent of yersiniosis, which can be contracted by ingestion of contaminated food. Yersinia secretes virulence factors to subvert critical pathways in the host cell. In this study we utilized shotgun label-free proteomics to study differential protein expression in epithelial cells infected with Y.enterocolitica. We identified a total of 551 proteins, amongst which 42 were downregulated (including Prostaglandin E Synthase 3, POH-1 and Karyopherin alpha) and 22 were upregulated (including Rab1 and RhoA) in infected cells. We validated some of these results by western blot analysis of proteins extracted from Caco-2 and HeLa cells. The proteomic dataset was used to identify host canonical pathways and molecular functions modulated by this infection in the host cells. This study constitutes a proteome of Yersinia-infected cells and can support new discoveries in the area of host-pathogen interactions. We describe a proteome of Yersinia enterocolitica-infected HeLa cells, including a description of specific proteins differentially expressed upon infection, molecular functions as well as pathways altered during infection. This proteomic study can lead to a better understanding of Y. enterocolitica pathogenesis in human epithelial cells. Copyright © 2016. Published by Elsevier B.V.

  8. Metabolomic differentiation of maca (Lepidium meyenii) accessions cultivated under different conditions using NMR and chemometric analysis.

    Science.gov (United States)

    Zhao, Jianping; Avula, Bharathi; Chan, Michael; Clément, Céline; Kreuzer, Michael; Khan, Ikhlas A

    2012-01-01

    To gain insights on the effects of color type, cultivation history, and growing site on the composition alterations of maca (Lepidium meyenii Walpers) hypocotyls, NMR profiling combined with chemometric analysis was applied to investigate the metabolite variability in different maca accessions. Maca hypocotyls with different colors (yellow, pink, violet, and lead-colored) cultivated at different geographic sites and different areas were examined for differences in metabolite expression. Differentiations of the maca accessions grown under the different cultivation conditions were determined by principle component analyses (PCAs) which were performed on the datasets derived from their ¹H NMR spectra. A total of 16 metabolites were identified by NMR analysis, and the changes in metabolite levels in relation to the color types and growing conditions of maca hypocotyls were evaluated using univariate statistical analysis. In addition, the changes of the correlation pattern among the metabolites identified in the maca accessions planted at the two different sites were examined. The results from both multivariate and univariate analysis indicated that the planting site was the major determining factor with regards to metabolite variations in maca hypocotyls, while the color of maca accession seems to be of minor importance in this respect. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Assessment of Textural Differentiations in Forest Resources in Romania Using Fractal Analysis

    Directory of Open Access Journals (Sweden)

    Ion Andronache

    2017-02-01

    Full Text Available Deforestation and forest degradation have several negative effects on the environment including a loss of species habitats, disturbance of the water cycle and reduced ability to retain CO2, with consequences for global warming. We investigated the evolution of forest resources from development regions in Romania affected by both deforestation and reforestation using a non-Euclidean method based on fractal analysis. We calculated four fractal dimensions of forest areas: the fractal box-counting dimension of the forest areas, the fractal box-counting dimension of the dilated forest areas, the fractal dilation dimension and the box-counting dimension of the border of the dilated forest areas. Fractal analysis revealed morpho-structural and textural differentiations of forested, deforested and reforested areas in development regions with dominant mountain relief and high hills (more forested and compact organization in comparison to the development regions dominated by plains or low hills (less forested, more fragmented with small and isolated clusters. Our analysis used the fractal analysis that has the advantage of analyzing the entire image, rather than studying local information, thereby enabling quantification of the uniformity, fragmentation, heterogeneity and homogeneity of forests.

  10. FIDEA: a server for the functional interpretation of differential expression analysis.

    KAUST Repository

    D'Andrea, Daniel; Grassi, Luigi; Mazzapioda, Mariagiovanna; Tramontano, Anna

    2013-01-01

    The results of differential expression analyses provide scientists with hundreds to thousands of differentially expressed genes that need to be interpreted in light of the biology of the specific system under study. This requires mapping the genes

  11. Differential Thermal Analysis and Dielectric Studies on 2-Methyl-2-Nitro-Propane under High Pressure

    Science.gov (United States)

    Büsing, D.; Jenau, M.; Reuter, J.; Würflinger, A.; Tamarit, J. Li.

    1995-05-01

    Differential thermal analysis and dielectric studies under pressures up to 300 MPa and temperatures of about 200 to 350 K have been performed on 2-methyl-2-nitro-propane (TBN). TBN displays an orientationally disordered phase (ODIC), solid I, and two non-plastic phases, solids II and III. The coexistence region of the plastic phase I increases with increasing pressure, whereas the low-temperature phase II apparently vanishes at a triple point I, II, III, above 300 MPa. The static permittivity increases on freezing, characterizing the solid I as an ODIC phase. In the frame of the Kirkwood-Onsager-Fröhlich theory the g-factor is about unity, discounting specific dielectric correlations. The dielectric behaviour of TBN is similar to previously studied related compounds, such as 2-chloro-2-methyl-propane or 2-brome- 2-methyl-propane

  12. Differentiation of minute virus of mice and mouse parvovirus by high resolution melting curve analysis.

    Science.gov (United States)

    Rao, Dan; Wu, Miaoli; Wang, Jing; Yuan, Wen; Zhu, Yujun; Cong, Feng; Xu, Fengjiao; Lian, Yuexiao; Huang, Bihong; Wu, Qiwen; Chen, Meili; Zhang, Yu; Huang, Ren; Guo, Pengju

    2017-12-01

    Murine parvovirus is one of the most prevalent infectious pathogens in mouse colonies. A specific primer pair targeting the VP2 gene of minute virus of mice (MVM) and mouse parvovirus (MPV) was utilized for high resolution melting (HRM) analysis. The resulting melting curves could distinguish these two virus strains and there was no detectable amplification of the other mouse pathogens which included rat parvovirus (KRV), ectromelia virus (ECT), mouse adenovirus (MAD), mouse cytomegalovirus (MCMV), polyoma virus (Poly), Helicobactor hepaticus (H. hepaticus) and Salmonella typhimurium (S. typhimurium). The detection limit of the standard was 10 copies/μL. This study showed that the PCR-HRM assay could be an alternative useful method with high specificity and sensitivity for differentiating murine parvovirus strains MVM and MPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Robustness of Operational Matrices of Differentiation for Solving State-Space Analysis and Optimal Control Problems

    Directory of Open Access Journals (Sweden)

    Emran Tohidi

    2013-01-01

    Full Text Available The idea of approximation by monomials together with the collocation technique over a uniform mesh for solving state-space analysis and optimal control problems (OCPs has been proposed in this paper. After imposing the Pontryagins maximum principle to the main OCPs, the problems reduce to a linear or nonlinear boundary value problem. In the linear case we propose a monomial collocation matrix approach, while in the nonlinear case, the general collocation method has been applied. We also show the efficiency of the operational matrices of differentiation with respect to the operational matrices of integration in our numerical examples. These matrices of integration are related to the Bessel, Walsh, Triangular, Laguerre, and Hermite functions.

  14. A Qualitative Analysis of Power Differentials in Ethical Situations in Academia

    Science.gov (United States)

    Gibson, Carter; Medeiros, Kelsey E.; Giorgini, Vincent; Mecca, Jensen T.; Devenport, Lynn D.; Connelly, Shane; Mumford, Michael D.

    2014-01-01

    Power and organizational hierarchies are ubiquitous to social institutions that form the foundation of modern society. Power differentials may act to constrain or enhance people's ability to make good ethical decisions. However, little scholarly work has examined perceptions of this important topic. The present effort seeks to address this issue by interviewing academics about hypothetical ethical problems that involve power differences among those involved. Academics discussed what they would do in these scenarios, often drawing on their own experiences. Using a think-aloud protocol, participants were prompted to discuss their reasoning and thinking behind their ethical decisions. These interview data were content analyzed using a semantic analysis program that identified a number of distinct ways that academics think about power differences and abuses in ethical situations. Implications of these findings are discussed. PMID:25356066

  15. Numerical bifurcation analysis of delay differential equations arising from physiological modeling.

    Science.gov (United States)

    Engelborghs, K; Lemaire, V; Bélair, J; Roose, D

    2001-04-01

    This paper has a dual purpose. First, we describe numerical methods for continuation and bifurcation analysis of steady state solutions and periodic solutions of systems of delay differential equations with an arbitrary number of fixed, discrete delays. Second, we demonstrate how these methods can be used to obtain insight into complex biological regulatory systems in which interactions occur with time delays: for this, we consider a system of two equations for the plasma glucose and insulin concentrations in a diabetic patient subject to a system of external assistance. The model has two delays: the technological delay of the external system, and the physiological delay of the patient's liver. We compute stability of the steady state solution as a function of two parameters, compare with analytical results and compute several branches of periodic solutions and their stability. These numerical results allow to infer two categories of diabetic patients for which the external system has different efficiency.

  16. New methodology developed for the differential scanning calorimetry analysis of polymeric matrixes incorporating phase change materials

    International Nuclear Information System (INIS)

    Barreneche, Camila; Solé, Aran; Miró, Laia; Martorell, Ingrid; Cabeza, Luisa F; Fernández, A Inés

    2012-01-01

    Nowadays, thermal comfort needs in buildings have led to an increase in energy consumption of the residential and service sectors. For this reason, thermal energy storage is shown as an alternative to achieve reduction of this high consumption. Phase change materials (PCM) have been studied to store energy due to their high storage capacity. A polymeric material capable of macroencapsulating PCM was developed by the authors of this paper. However, difficulties were found while measuring the thermal properties of these materials by differential scanning calorimetry (DSC). The polymeric matrix interferes in the detection of PCM properties by DSC. To remove this interfering effect, a new methodology which replaces the conventional empty crucible used as a reference in the DSC analysis by crucibles composed of the polymeric matrix was developed. Thus, a clear signal from the PCM is obtained by subtracting the new full crucible signal from the sample signal. (paper)

  17. A three-dimensional layerwise-differential quadrature free vibration analysis of laminated cylindrical shells

    Energy Technology Data Exchange (ETDEWEB)

    Malekzadeh, P. [Department of Mechanical Engineering, Persian Gulf University, Boushehr 75168 (Iran, Islamic Republic of); Center of Excellence for Computational Mechanics in Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of)], E-mail: malekzadeh@pgu.ac.ir; Farid, M. [Center of Excellence for Computational Mechanics in Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of); Department of Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of); Zahedinejad, P. [Department of Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of)

    2008-07-15

    A mixed layerwise theory and differential quadrature (DQ) method (LW-DQ) for three-dimensional free vibration analysis of arbitrary laminated circular cylindrical shells is introduced. Using the layerwise theory in conjunction with the three-dimensional form of Hamilton's principle, the transversely discretized equations of motion and the related boundary conditions are obtained. Then, the DQ method is employed to discretize the resulting equations in the axial directions. The fast convergence behavior of the method is demonstrated and its accuracy is verified by comparing the results with those of other shell theories obtained using conventional methods and also with those of ANSYS software. In the case of arbitrary laminated shells with simply supported ends, the exact solution is developed for comparison purposes. It is shown that using few DQ grid points, converged accurate solutions are obtained. Less computational efforts of the proposed approach with respect to ANSYS software is shown.

  18. A Posteriori Error Analysis of Stochastic Differential Equations Using Polynomial Chaos Expansions

    KAUST Repository

    Butler, T.; Dawson, C.; Wildey, T.

    2011-01-01

    We develop computable a posteriori error estimates for linear functionals of a solution to a general nonlinear stochastic differential equation with random model/source parameters. These error estimates are based on a variational analysis applied to stochastic Galerkin methods for forward and adjoint problems. The result is a representation for the error estimate as a polynomial in the random model/source parameter. The advantage of this method is that we use polynomial chaos representations for the forward and adjoint systems to cheaply produce error estimates by simple evaluation of a polynomial. By comparison, the typical method of producing such estimates requires repeated forward/adjoint solves for each new choice of random parameter. We present numerical examples showing that there is excellent agreement between these methods. © 2011 Society for Industrial and Applied Mathematics.

  19. ANALYSIS OF A DIFFERENTIATED APPROACH TO THE APPOINTMENT OF DICK METHODS IN BIOFEEDBACK CORRECTION AUTONOMIC DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    A. G. Polyakova

    2013-01-01

    Full Text Available Goal of research: analysis of the effectiveness of Biofeedback therapy is differentiated depending on the clinical forms of autonomic dysfunction. Exchange rate control efficacy of biofeedback hardware was conducted on the dynamics of clinical andl aboratory data, surveys and assessment of the functional State of the SNC using heart rate variability, vegetative resonance test, Kerdo index definition, as well as èlektrokardiografiče applications and questionnaires, characterizing the State of psychoemotional sphere (Spilbergera–Hanina, test, Luscher. Laboratory tests include a complete blood count with evaluation of Adaptive reactions of the organism. The results of the rehabilitation complex of the patients with the use of biofeedback have confirmed its effectiveness.

  20. The analysis of linear partial differential operators I distribution theory and Fourier analysis

    CERN Document Server

    Hörmander, Lars

    2003-01-01

    The main change in this edition is the inclusion of exercises with answers and hints. This is meant to emphasize that this volume has been written as a general course in modern analysis on a graduate student level and not only as the beginning of a specialized course in partial differen­ tial equations. In particular, it could also serve as an introduction to harmonic analysis. Exercises are given primarily to the sections of gen­ eral interest; there are none to the last two chapters. Most of the exercises are just routine problems meant to give some familiarity with standard use of the tools introduced in the text. Others are extensions of the theory presented there. As a rule rather complete though brief solutions are then given in the answers and hints. To a large extent the exercises have been taken over from courses or examinations given by Anders Melin or myself at the University of Lund. I am grateful to Anders Melin for letting me use the problems originating from him and for numerous valuable comm...

  1. A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells.

    Science.gov (United States)

    Ulfenborg, Benjamin; Karlsson, Alexander; Riveiro, Maria; Améen, Caroline; Åkesson, Karolina; Andersson, Christian X; Sartipy, Peter; Synnergren, Jane

    2017-01-01

    The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic- and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be used to structure

  2. A subpopulation of dopaminergic neurons co-expresses serotonin in ventral mesencephalic cultures but not after intrastriatal transplantation in a rat model of Parkinsons disease

    DEFF Research Database (Denmark)

    Di Santo, Stefano; Seiler, Stefanie; Ducray, Angélique

    2017-01-01

    Cell replacement therapy is a promising avenue into the investigation and treatment of Parkinson’s disease (PD) and in some cases significant long-term motor improvements have been demonstrated. The main source of donor tissue is the human fetal ventral mesencephalon (VM), which consists...... 30% of the dopaminergic neurons in the donor tissue co-expressed serotonin, no co-localization could be detected in grafts one month after intrastriatal transplantation into hemi-parkinsonian rats. In conclusion, a significant and susceptible sub-population of dopaminergic neurons in fetal VM tissues...... both fetal rat and human dissociated, organotypic and neurosphere VM cultures as well as an animal model of PD were investigated. In dissociated rat VM cultures approximately 30% of the TH positive neurons co-expressed serotonin, while no co-localization with GABA was observed. Interestingly, co...

  3. Data set for diet specific differential gene expression analysis in three Spodoptera moths

    Directory of Open Access Journals (Sweden)

    A. Roy

    2016-09-01

    Full Text Available Examination of closely related species pairs is suggested for evolutionary comparisons of different degrees of polyphagy, which we did here with three taxa of lepidopteran herbivores, Spodoptera spp (S. littoralis, S. frugiperda maize (C and rice (R strains for a RNAseq analysis of the midguts from the 3rd instar insect larvae for differential metabolic responses after feeding on pinto bean based artificial diet vs maize leaves. Paired-end (2×100 bp Illumina HiSeq2500 sequencing resulted in a total of 24, 23, 24, and 21 million reads for the SF-C-Maize, SF-C-Pinto, SF-R-Maize, SF-R Pinto, and a total of 35 and 36 million reads for the SL-Maize and SL-Pinto samples, respectively. After quality control measures, a total of 62.2 million reads from SL and 71.7 million reads from SF were used for transcriptome assembly (TA. The resulting final de novo reference TA (backbone for the SF taxa contained 37,985 contigs with a N50 contig size of 1030 bp and a maximum contig length of 17,093 bp, while for SL, 28,329 contigs were generated with a N50 contig size of 1980 bp and a maximum contig length of 18,267 bp. The data presented herein contains supporting information related to our research article Roy et al. (2016 http://dx.doi.org/10.1016/j.ibmb.2016.02.006 [1]. Keywords: Differential expression analysis (DGE, Transcriptomics, Spodoptera, Adaptation, Generalist, Specialist, RPKM (reads per kilo base of transcript per million mapped reads, RNA seq

  4. A Genome-Wide Association Study for Culm Cellulose Content in Barley Reveals Candidate Genes Co-Expressed with Members of the CELLULOSE SYNTHASE A Gene Family

    Science.gov (United States)

    Houston, Kelly; Burton, Rachel A.; Sznajder, Beata; Rafalski, Antoni J.; Dhugga, Kanwarpal S.; Mather, Diane E.; Taylor, Jillian; Steffenson, Brian J.; Waugh, Robbie; Fincher, Geoffrey B.

    2015-01-01

    Cellulose is a fundamentally important component of cell walls of higher plants. It provides a scaffold that allows the development and growth of the plant to occur in an ordered fashion. Cellulose also provides mechanical strength, which is crucial for both normal development and to enable the plant to withstand both abiotic and biotic stresses. We quantified the cellulose concentration in the culm of 288 two – rowed and 288 six – rowed spring type barley accessions that were part of the USDA funded barley Coordinated Agricultural Project (CAP) program in the USA. When the population structure of these accessions was analysed we identified six distinct populations, four of which we considered to be comprised of a sufficient number of accessions to be suitable for genome-wide association studies (GWAS). These lines had been genotyped with 3072 SNPs so we combined the trait and genetic data to carry out GWAS. The analysis allowed us to identify regions of the genome containing significant associations between molecular markers and cellulose concentration data, including one region cross-validated in multiple populations. To identify candidate genes we assembled the gene content of these regions and used these to query a comprehensive RNA-seq based gene expression atlas. This provided us with gene annotations and associated expression data across multiple tissues, which allowed us to formulate a supported list of candidate genes that regulate cellulose biosynthesis. Several regions identified by our analysis contain genes that are co-expressed with CELLULOSE SYNTHASE A (HvCesA) across a range of tissues and developmental stages. These genes are involved in both primary and secondary cell wall development. In addition, genes that have been previously linked with cellulose synthesis by biochemical methods, such as HvCOBRA, a gene of unknown function, were also associated with cellulose levels in the association panel. Our analyses provide new insights into the

  5. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis

    Directory of Open Access Journals (Sweden)

    Yang X

    2018-03-01

    Full Text Available Xiao Yang,1 Shaoming Zhu,2 Li Li,3 Li Zhang,1 Shu Xian,1 Yanqing Wang,1 Yanxiang Cheng1 1Department of Obstetrics and Gynecology, 2Department of Urology, Renmin Hospital of Wuhan University, 3Department of Pharmacology, Wuhan University Health Science Center, Wuhan, Hubei, People’s Republic of China Background: The mortality rate associated with ovarian cancer ranks the highest among gynecological malignancies. However, the cause and underlying molecular events of ovarian cancer are not clear. Here, we applied integrated bioinformatics to identify key pathogenic genes involved in ovarian cancer and reveal potential molecular mechanisms. Results: The expression profiles of GDS3592, GSE54388, and GSE66957 were downloaded from the Gene Expression Omnibus (GEO database, which contained 115 samples, including 85 cases of ovarian cancer samples and 30 cases of normal ovarian samples. The three microarray datasets were integrated to obtain differentially expressed genes (DEGs and were deeply analyzed by bioinformatics methods. The gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichments of DEGs were performed by DAVID and KOBAS online analyses, respectively. The protein–protein interaction (PPI networks of the DEGs were constructed from the STRING database. A total of 190 DEGs were identified in the three GEO datasets, of which 99 genes were upregulated and 91 genes were downregulated. GO analysis showed that the biological functions of DEGs focused primarily on regulating cell proliferation, adhesion, and differentiation and intracellular signal cascades. The main cellular components include cell membranes, exosomes, the cytoskeleton, and the extracellular matrix. The molecular functions include growth factor activity, protein kinase regulation, DNA binding, and oxygen transport activity. KEGG pathway analysis showed that these DEGs were mainly involved in the Wnt signaling pathway, amino acid metabolism, and the

  6. Bioinformatics analysis of differentially expressed proteins in prostate cancer based on proteomics data

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-03-01

    Full Text Available Chen Chen,1 Li-Guo Zhang,1 Jian Liu,1 Hui Han,1 Ning Chen,1 An-Liang Yao,1 Shao-San Kang,1 Wei-Xing Gao,1 Hong Shen,2 Long-Jun Zhang,1 Ya-Peng Li,1 Feng-Hong Cao,1 Zhi-Guo Li3 1Department of Urology, North China University of Science and Technology Affiliated Hospital, 2Department of Modern Technology and Education Center, 3Department of Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, People’s Republic of China Abstract: We mined the literature for proteomics data to examine the occurrence and metastasis of prostate cancer (PCa through a bioinformatics analysis. We divided the differentially expressed proteins (DEPs into two groups: the group consisting of PCa and benign tissues (P&b and the group presenting both high and low PCa metastatic tendencies (H&L. In the P&b group, we found 320 DEPs, 20 of which were reported more than three times, and DES was the most commonly reported. Among these DEPs, the expression levels of FGG, GSN, SERPINC1, TPM1, and TUBB4B have not yet been correlated with PCa. In the H&L group, we identified 353 DEPs, 13 of which were reported more than three times. Among these DEPs, MDH2 and MYH9 have not yet been correlated with PCa metastasis. We further confirmed that DES was differentially expressed between 30 cancer and 30 benign tissues. In addition, DEPs associated with protein transport, regulation of actin cytoskeleton, and the extracellular matrix (ECM–receptor interaction pathway were prevalent in the H&L group and have not yet been studied in detail in this context. Proteins related to homeostasis, the wound-healing response, focal adhesions, and the complement and coagulation pathways were overrepresented in both groups. Our findings suggest that the repeatedly reported DEPs in the two groups may function as potential biomarkers for detecting PCa and predicting its aggressiveness. Furthermore

  7. Riemann type algebraic structures and their differential-algebraic integrability analysis

    Directory of Open Access Journals (Sweden)

    Prykarpatsky A.K.

    2010-06-01

    Full Text Available The differential-algebraic approach to studying the Lax type integrability of generalized Riemann type equations is devised. The differentiations and the associated invariant differential ideals are analyzed in detail. The approach is also applied to studying the Lax type integrability of the well known Korteweg-de Vries dynamical system.

  8. Co-expression of NCED and ALO improves vitamin C level and tolerance to drought and chilling in transgenic tobacco and stylo plants.

    Science.gov (United States)

    Bao, Gegen; Zhuo, Chunliu; Qian, Chunmei; Xiao, Ting; Guo, Zhenfei; Lu, Shaoyun

    2016-01-01

    Abscisic acid (ABA) regulates plant adaptive responses to various environmental stresses, while L-ascorbic acid (AsA) that is also named vitamin C is an important antioxidant and involves in plant stress tolerance and the immune system in domestic animals. Transgenic tobacco (Nicotiana tabacum L.) and stylo [Stylosanthes guianensis (Aublet) Swartz], a forage legume, plants co-expressing stylo 9-cis-epoxycarotenoid dioxygenase (SgNCED1) and yeast D-arabinono-1,4-lactone oxidase (ALO) genes were generated in this study, and tolerance to drought and chilling was analysed in comparison with transgenic tobacco overexpressing SgNCED1 or ALO and the wild-type plants. Compared to the SgNCED1 or ALO transgenic plants, in which only ABA or AsA levels were increased, both ABA and AsA levels were increased in transgenic tobacco and stylo plants co-expressing SgNCED1 and ALO genes. Compared to the wild type, an enhanced drought tolerance was observed in SgNCED1 transgenic tobacco plants with induced expression of drought-responsive genes, but not in ALO plants, while an enhanced chilling tolerance was observed in ALO transgenic tobaccos with induced expression of cold-responsive genes, but not in SgNCED1 plants. Co-expression of SgNCED1 and ALO genes resulted in elevated tolerance to both drought and chilling in transgenic tobacco and stylo plants with induced expression of both drought and cold-responsive genes. Our result suggests that co-expression of SgNCED1 and ALO genes is an effective way for use in forage plant improvement for increased tolerance to drought and chilling and nutrition quality. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  9. High versus low radioiodine activity in patients with differentiated thyroid cancer - A meta-analysis

    International Nuclear Information System (INIS)

    Valachis, Antonis; Nearchou, Andreas

    2013-01-01

    Background: The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design: A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results: Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85 - 1.04, p-value 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72 - 1.06, p-value 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93 - 1.07, p-value 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion: Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity

  10. High versus low radioiodine activity in patients with differentiated thyroid cancer - A meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Valachis, Antonis [Dept. of Oncology, Maelarsjukhuset., Eskilstuna (Sweden); Univ. of Uppsala,, (Sweden)], e-mail: Valachis@hotmail.com, Antonis.Valachis@akademiska.uu.se; Nearchou, Andreas [Dept, of Oncology, Maelarsjukhuset., Eskilstuna (Sweden); Univ. of Uppsala., Uppsala (Sweden)

    2013-08-15

    Background: The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design: A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results: Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85 - 1.04, p-value 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72 - 1.06, p-value 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93 - 1.07, p-value 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion: Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity.

  11. Chemical Differentiation of Osseous, Dental, and Non-skeletal Materials in Forensic Anthropology using Elemental Analysis.

    Science.gov (United States)

    Zimmerman, Heather A; Meizel-Lambert, Cayli J; Schultz, John J; Sigman, Michael E

    2015-03-01

    Forensic anthropologists are generally able to identify skeletal materials (bone and tooth) using gross anatomical features; however, highly fragmented or taphonomically altered materials may be problematic to identify. Several chemical analysis techniques have been shown to be reliable laboratory methods that can be used to determine if questionable fragments are osseous, dental, or non-skeletal in nature. The purpose of this review is to provide a detailed background of chemical analysis techniques focusing on elemental compositions that have been assessed for use in differentiating osseous, dental, and non-skeletal materials. More recently, chemical analysis studies have also focused on using the elemental composition of osseous/dental materials to evaluate species and provide individual discrimination, but have generally been successful only in small, closed groups, limiting their use forensically. Despite significant advances incorporating a variety of instruments, including handheld devices, further research is necessary to address issues in standardization, error rates, and sample size/diversity. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Differential item functioning analysis of the Vanderbilt Expertise Test for cars.

    Science.gov (United States)

    Lee, Woo-Yeol; Cho, Sun-Joo; McGugin, Rankin W; Van Gulick, Ana Beth; Gauthier, Isabel

    2015-01-01

    The Vanderbilt Expertise Test for cars (VETcar) is a test of visual learning for contemporary car models. We used item response theory to assess the VETcar and in particular used differential item functioning (DIF) analysis to ask if the test functions the same way in laboratory versus online settings and for different groups based on age and gender. An exploratory factor analysis found evidence of multidimensionality in the VETcar, although a single dimension was deemed sufficient to capture the recognition ability measured by the test. We selected a unidimensional three-parameter logistic item response model to examine item characteristics and subject abilities. The VETcar had satisfactory internal consistency. A substantial number of items showed DIF at a medium effect size for test setting and for age group, whereas gender DIF was negligible. Because online subjects were on average older than those tested in the lab, we focused on the age groups to conduct a multigroup item response theory analysis. This revealed that most items on the test favored the younger group. DIF could be more the rule than the exception when measuring performance with familiar object categories, therefore posing a challenge for the measurement of either domain-general visual abilities or category-specific knowledge.

  13. Analysis of cross-population differentiation between Thoroughbred and Jeju horses.

    Science.gov (United States)

    Lee, Wonseok; Shin, Donghyn; Taye, Mengistie; Lee, Chul; Kim, Heebal; Lee, Hak-Kyo; Park, Kyung-Do

    2017-12-19

    This study was intended to identify genes positively selected in Thoroughbred horses (THBs) that potentially contribute to their running performances. The genomes of THB and Jeju horses (JH, Korean native horse) were compared to identify genes positively selected in THB. We performed cross-population extended haplotype homozygosity (XP-EHH) and cross-population composite likelihood ratio test (XP-CLR) statistical methods for our analysis using whole genome resequencing data of 14 THB and 6 JH. We identified 98 (XP-EHH) and 200 (XP-CLR) genes that are under positive selection in THB. Gene enrichment analysis identified 72 BP terms. The genes and BP terms explained some of THB's characteristics such as immunity, energy metabolism and eye size and function related to running performances. GO terms that play key roles in several cell signaling mechanisms, which affected ocular size and visual functions were identified. GO term Eye photoreceptor cell differentiation is among the terms annotated presumed to affect eye size. Our analysis revealed some positively selected candidate genes in THB related to their racing performances. The genes detected are related to the immunity, ocular size and function, and energy metabolism.

  14. Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

    Science.gov (United States)

    García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.

    2015-01-01

    Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422

  15. Co-expression of D-glucose isomerase and D-psicose 3-epimerase: development of an efficient one-step production of D-psicose.

    Science.gov (United States)

    Men, Yan; Zhu, Yueming; Zeng, Yan; Izumori, Ken; Sun, Yuanxia; Ma, Yanhe

    2014-10-01

    D-Psicose has been attracting attention in recent years because of its alimentary activities and is used as an ingredient in a range of foods and dietary supplements. To develop a one-step enzymatic process of D-psicose production, thermoactive D-glucose isomerase and the D-psicose 3-epimerase obtained from Bacillus sp. and Ruminococcus sp., respectively, were successfully co-expressed in Escherichia coli BL21 strain. The substrate of one-step enzymatic process was D-glucose. The co-expression system exhibited maximum activity at 65 °C and pH 7.0. Mg(2+) could enhance the output of D-psicose by 2.32 fold to 1.6 g/L from 10 g/L of D-glucose. When using high-fructose corn syrup (HFCS) as substrate, 135 g/L D-psicose was produced under optimum conditions. The mass ratio of D-glucose, D-fructose, and D-psicose was almost 3.0:2.7:1.0, when the reaction reached equilibrium after an 8h incubation time. This co-expression system approaching to produce D-psicose has potential application in food and beverage products, especially softdrinks. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma

    International Nuclear Information System (INIS)

    Põlajeva, Jelena; Swartling, Fredrik J; Jiang, Yiwen; Singh, Umashankar; Pietras, Kristian; Uhrbom, Lene; Westermark, Bengt; Roswall, Pernilla

    2012-01-01

    MicroRNAs (miRNAs) and their role during tumor development have been studied in great detail during the last decade, albeit their expression pattern and regulation during normal development are however not so well established. Previous studies have shown that miRNAs are differentially expressed in solid human tumors. Platelet-derived growth factor (PDGF) signaling is known to be involved in normal development of the brain as well as in malignant primary brain tumors, gliomas, but the complete mechanism is still lacking. We decided to investigate the expression of the oncogenic miR-21 during normal mouse development and glioma, focusing on PDGF signaling as a potential regulator of miR-21. We generated mouse glioma using the RCAS/tv-a system for driving PDGF-BB expression in a cell-specific manner. Expression of miR-21 in mouse cell cultures and mouse brain were assessed using Northern blot analysis and in situ hybridization. Immunohistochemistry and Western blot analysis were used to investigate SOX2 expression. LNA-modified siRNA was used for irreversible depletion of miR-21. For inhibition of PDGF signaling Gleevec (imatinib mesylate), Rapamycin and U0126, as well as siRNA were used. Statistical significance was calculated using double-sided unpaired Student´s t-test. We identified miR-21 to be highly expressed during embryonic and newborn brain development followed by a gradual decrease until undetectable at postnatal day 7 (P7), this pattern correlated with SOX2 expression. Furthermore, miR-21 and SOX2 showed up-regulation and overlapping expression pattern in RCAS/tv-a generated mouse brain tumor specimens. Upon irreversible depletion of miR-21 the expression of SOX2 was strongly diminished in both mouse primary glioma cultures and human glioma cell lines. Interestingly, in normal fibroblasts the expression of miR-21 was induced by PDGF-BB, and inhibition of PDGF signaling in mouse glioma primary cultures resulted in suppression of miR-21 suggesting that mi

  17. Cell differentiation in cardiac myxomas: confocal microscopy and gene expression analysis after laser capture microdissection.

    Science.gov (United States)

    Pucci, Angela; Mattioli, Claudia; Matteucci, Marco; Lorenzini, Daniele; Panvini, Francesca; Pacini, Simone; Ippolito, Chiara; Celiento, Michele; De Martino, Andrea; Dolfi, Amelio; Belgio, Beatrice; Bortolotti, Uberto; Basolo, Fulvio; Bartoloni, Giovanni

    2018-05-22

    Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy. Gene expression analyses of α-smooth muscle actin, endothelial CD31 antigen, alpha-cardiac actin, matrix metalloprotease-2 (MMP2) and tissue inhibitor of matrix metalloprotease-1 (TIMP1) was performed on cDNA obtained from either microdissected neoplastic cells or whole tumor sections. We found very little or absent CD31 and α-Smooth Muscle Actin expression in the microdissected cells as compared to the whole tumors, whereas TIMP1 and MMP2 genes were highly expressed in both ones, greater levels being found in patients with embolic phenomena. α-Cardiac Actin was not detected. Confocal microscopy disclosed two different signals corresponding to calretinin-positive myxoma cells and to endothelial CD31-positive cells, respectively. In conclusion, the neoplastic (lepidic) cells showed a distinct gene expression pattern and no consistent overlapping with endothelial and smooth muscle cells or cardiac myocytes; the expression of TIMP1 and MMP2 might be related to clinical presentation; larger series studies using also systematic transcriptome analysis might be useful to confirm the present results.

  18. A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells.

    Science.gov (United States)

    Magistri, Marco; Khoury, Nathalie; Mazza, Emilia Maria Cristina; Velmeshev, Dmitry; Lee, Jae K; Bicciato, Silvio; Tsoulfas, Pantelis; Faghihi, Mohammad Ali

    2016-11-01

    Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of specific molecular markers and by the difficulties associated with purifying and culturing astrocytes from adult human brains. Human neural progenitor cells (NPCs) with self-renewal and multipotent properties represent an appealing model system to gain insight into the developmental genetics and function of human astrocytes, but a comprehensive molecular characterization that confirms the validity of this cellular system is still missing. Here we used an unbiased transcriptomic analysis to characterize in vitro culture of human NPCs and to define the gene expression programs activated during the differentiation of these cells into astrocytes using FBS or the combination of CNTF and BMP4. Our results demonstrate that in vitro cultures of human NPCs isolated during the gliogenic phase of neurodevelopment mainly consist of radial glial cells (RGCs) and glia-restricted progenitor cells. In these cells the combination of CNTF and BMP4 activates the JAK/STAT and SMAD signaling cascades, leading to the inhibition of oligodendrocytes lineage commitment and activation of astrocytes differentiation. On the other hand, FBS-derived astrocytes have properties of reactive astrocytes. Our work suggests that in vitro culture of human NPCs represents a valuable cellular system to study human disorders characterized by impairment of astrocytes development and function. Our datasets represent an important resource for researchers studying human astrocytes development and might set the basis for the discovery of novel human-specific astrocyte markers. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. NMR-based lipidomic analysis of blood lipoproteins differentiates the progression of coronary heart disease.

    Science.gov (United States)

    Kostara, Christina E; Papathanasiou, Athanasios; Psychogios, Nikolaos; Cung, Manh Thong; Elisaf, Moses S; Goudevenos, John; Bairaktari, Eleni T

    2014-05-02

    Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.

  20. Constraining cosmic scatter in the Galactic halo through a differential analysis of metal-poor stars

    Science.gov (United States)

    Reggiani, Henrique; Meléndez, Jorge; Kobayashi, Chiaki; Karakas, Amanda; Placco, Vinicius

    2017-12-01

    Context. The chemical abundances of metal-poor halo stars are important to understanding key aspects of Galactic formation and evolution. Aims: We aim to constrain Galactic chemical evolution with precise chemical abundances of metal-poor stars (-2.8 ≤ [Fe/H] ≤ -1.5). Methods: Using high resolution and high S/N UVES spectra of 23 stars and employing the differential analysis technique we estimated stellar parameters and obtained precise LTE chemical abundances. Results: We present the abundances of Li, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Zn, Sr, Y, Zr, and Ba. The differential technique allowed us to obtain an unprecedented low level of scatter in our analysis, with standard deviations as low as 0.05 dex, and mean errors as low as 0.05 dex for [X/Fe]. Conclusions: By expanding our metallicity range with precise abundances from other works, we were able to precisely constrain Galactic chemical evolution models in a wide metallicity range (-3.6 ≤ [Fe/H] ≤ -0.4). The agreements and discrepancies found are key for further improvement of both models and observations. We also show that the LTE analysis of Cr II is a much more reliable source of abundance for chromium, as Cr I has important NLTE effects. These effects can be clearly seen when we compare the observed abundances of Cr I and Cr II with GCE models. While Cr I has a clear disagreement between model and observations, Cr II is very well modeled. We confirm tight increasing trends of Co and Zn toward lower metallicities, and a tight flat evolution of Ni relative to Fe. Our results strongly suggest inhomogeneous enrichment from hypernovae. Our precise stellar parameters results in a low star-to-star scatter (0.04 dex) in the Li abundances of our sample, with a mean value about 0.4 dex lower than the prediction from standard Big Bang nucleosynthesis; we also study the relation between lithium depletion and stellar mass, but it is difficult to assess a correlation due to the limited mass range. We

  1. Infections in the differential diagnosis of Bell's palsy: a plea for performing CSF analysis.

    Science.gov (United States)

    Henkel, Katrin; Lange, Peter; Eiffert, Helmut; Nau, Roland; Spreer, Annette

    2017-04-01

    Peripheral facial nerve palsy (FP) is the most common single nerve affection. Most cases are idiopathic, but a relevant fraction is caused by potentially treatable aetiologies including infections. Not all current diagnosis and treatment guidelines recommend routine cerebrospinal fluid (CSF) analysis in the diagnostic workup of this symptom. In this study, we evaluated frequency of aetiologies and relevance of CSF analysis in an interdisciplinary cohort. We retrospectively analysed all cases of newly diagnosed FP treated at a German university medical centre in a 3-year period. Diagnostic certainty was classified for infectious aetiologies according to clinical and CSF parameters. 380 patients with FP were identified, 63 children and 317 adults. Idiopathic Bell´s palsy was predominant in 61 %. 25 % of FP was attributed to infections, and other causes were identified in 14 %. Clinical presentation alone was not conclusive for infectious aetiology, in almost half of patients with infection-attributed FP the reported symptoms or clinical signs did not differ from common symptoms of idiopathic Bell`s palsy. Determination of C-reactive protein or white blood cell count was not helpful in the identification of infectious causes, and radiological imaging was performed in a high proportion of adult patients without conclusive results. Nuchal rigidity was found only in 7 % of patients with CSF pleocytosis. The predominant infectious agents were Borrelia burgdorferi, VZV and HSV, and in most of these cases diagnosis relied on the findings of CSF analysis. This study outlines the importance of careful differential diagnosis to identify infectious causes of facial nerve palsy. The high incidence and frequent unspecific clinical presentation of infectious FP underlines the importance of including CSF analysis in the diagnostic routine workup of FP.

  2. Differential proteiomic analysis of mouse intestinal epithelium irradiated by γ-ray

    International Nuclear Information System (INIS)

    Zhang Bo; Su Yongping; Liu Xiaohong; Ai Guoping; Ran Xinze; Wei Yongjiang; Wang Junping; Cheng Tianmin

    2003-01-01

    Objective: For elucidating the molecular mechanism of reconstruction of intestinal epithelium damaged by ionizing radiation, the proteomes of murine intestinal epithelium from normal and irradiated mice were compared by 2-D electrophoresis. Methods: Histopathologic sections of whole small intestine made from BALB/c mice 3 h and 72 h after total-body irradiation were stained with hematoxylin-eosin. Intestinal epithelial cells were isolated from normal and irradiated mice. The total protein samples prepared by one-step method were used in 2-D electrophoresis, the protein maps were compared and the differential spots were detected with PDQuest analysis software. Twenty-eight different spots were cut off from the gels, digested in gel with trypsin, measured with MALDI-TOF-MS and searched in database. Results: Small intestinal epithelium was damaged as early as 3 h after irradiation, and reconstructed 72 h later. After Coomassie-staining, the 2-DE image analysis by PDQuest software detected 638 ± 39 protein spots in normal mice group, 566 ± 32 spots in 3 hours post irradiation group, and 591 ± 29 spots in 3 days post irradiation group. The 2-DE images showed that proteomes of intestinal epithelium were altered with γ-irradiation. The proteins identified by peptide mass fingerprinting involved in cellular events, including signal transduction, metabolism and oxidative stress responses. Conclusions: Gamma-irradiation can induce the protein expression of intestinal epithelium. The technique of 2-D electrophoresis is a useful tool in the study of molecular mechanism of radiation damage

  3. Analysis of gene expression during odontogenic differentiation of cultured human dental pulp cells

    Directory of Open Access Journals (Sweden)

    Min-Seock Seo

    2012-08-01

    Full Text Available Objectives We analyzed gene-expression profiles after 14 day odontogenic induction of human dental pulp cells (DPCs using a DNA microarray and sought candidate genes possibly associated with mineralization. Materials and Methods Induced human dental pulp cells were obtained by culturing DPCs in odontogenic induction medium (OM for 14 day. Cells exposed to normal culture medium were used as controls. Total RNA was extracted from cells and analyzed by microarray analysis and the key results were confirmed selectively by reverse-transcriptase polymerase chain reaction (RT-PCR. We also performed a gene set enrichment analysis (GSEA of the microarray data. Results Six hundred and five genes among the 47,320 probes on the BeadChip differed by a factor of more than two-fold in the induced cells. Of these, 217 genes were upregulated, and 388 were down-regulated. GSEA revealed that in the induced cells, genes implicated in Apoptosis and Signaling by wingless MMTV integration (Wnt were significantly upregulated. Conclusions Genes implicated in Apoptosis and Signaling by Wnt are highly connected to the differentiation of dental pulp cells into odontoblast.

  4. Intestinal transcriptome analysis revealed differential salinity adaptation between two tilapiine species.

    Science.gov (United States)

    Ronkin, Dana; Seroussi, Eyal; Nitzan, Tali; Doron-Faigenboim, Adi; Cnaani, Avner

    2015-03-01

    Tilapias are a group of freshwater species, which vary in their ability to adapt to high salinity water. Osmotic regulation in fish is conducted mainly in the gills, kidney, and gastrointestinal tract (GIT). The mechanisms involved in ion and water transport through the GIT is not well-characterized, with only a few described complexes. Comparing the transcriptome of the anterior and posterior intestinal sections of a freshwater and saltwater adapted fish by deep-sequencing, we examined the salinity adaptation of two tilapia species: the high salinity-tolerant Oreochromis mossambicus (Mozambique tilapia), and the less salinity-tolerant Oreochromis niloticus (Nile tilapia). This comparative analysis revealed high similarity in gene expression response to salinity change between species in the posterior intestine and large differences in the anterior intestine. Furthermore, in the anterior intestine 68 genes were saltwater up-regulated in one species and down-regulated in the other species (47 genes up-regulated in O. niloticus and down-regulated in O. mossambicus, with 21 genes showing the reverse pattern). Gene ontology (GO) analysis showed a high proportion of transporter and ion channel function among these genes. The results of this study point to a group of genes that differed in their salinity-dependent regulation pattern in the anterior intestine as potentially having a role in the differential salinity tolerance of these two closely related species. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Trace analysis of lead and cadmium in seafoods by differential pulse anodic stripping voltametry

    International Nuclear Information System (INIS)

    Sumera, F.C.; Verceluz, F.P.; Kapauan, P.A.

    1979-01-01

    A method for the simultaneous determination of cadmium and lead in seafoods is described. The sample is dry ashed in a muffle furnace elevating the temperature gradually up to 500 0 C. The ashed sample is treated with concentrated nitric acid, dried on a heating plate and returned to the muffle furnace for further heating. The treated ash is then dissolved in 1 N HCL acetate buffer and citric acid are added and the pH adjusted to 3.6-4. The resulting solution is analyzed for lead and cadmium by differential pulse anodic stripping voltametry (DPASV) using a wax-impregnated graphite thin film electrode. The average recoveries of 0.4 of cadmium and lead added to 5 fish samples were 97% and 99% respectively. The standard deviations, on a homogenized shark sample for lead and cadmium analysis were 6.7 ppb and 12.3 ppb, respectively, and the relative standard deviations were 21.0% and 15.5% respectively. Studies on instrumental parameters involved in the DPASV step of analysis and methods of measuring peak current signals were also made. (author)

  6. Phytolith analysis for differentiating between foxtail millet (Setaria italica) and green foxtail (Setaria viridis).

    Science.gov (United States)

    Zhang, Jianping; Lu, Houyuan; Wu, Naiqin; Yang, Xiaoyan; Diao, Xianmin

    2011-05-06

    Foxtail millet (Setaria italica) is one of the oldest domesticated cereal crops in Eurasia, but identifying foxtail millets, especially in charred grains, and differentiating it from its wild ancestor, green foxtail (Setaria viridis), in the archaeobotanical remains, is still problematic. Phytolithic analysis provides a meaningful method for identifying this important crop. In this paper, the silicon structure patterns in the glumes, lemmas, and paleas from inflorescence bracts in 16 modern plants of foxtail millet and green foxtail from China and Europe are examined using light microscopy with phase-contrast and a microscopic interferometer. Our research shows that the silicon structure of ΩIII from upper lemmas and paleas in foxtail millet and green foxtail can be correspondingly divided into two groups. The size of ΩIII type phytolith of foxtail millet is bigger than that from green foxtail. Discriminant function analysis reveals that 78.4% of data on foxtail millet and 76.9% of data on green foxtail are correctly classified. This means certain morphotypes of phytoliths are relatively reliable tools for distinguishing foxtail millet from green foxtail. Our results also revealed that the husk phytolith morphologies of foxtail millets from China and Eastern Europe are markedly different from those from Western Europe. Our research gives a meaningful method of separating foxtail millet and green foxtail. The implications of these findings for understanding the history of foxtail millet domestication and cultivation in ancient civilizations are significant.

  7. Phytolith analysis for differentiating between foxtail millet (Setaria italica and green foxtail (Setaria viridis.

    Directory of Open Access Journals (Sweden)

    Jianping Zhang

    2011-05-01

    Full Text Available Foxtail millet (Setaria italica is one of the oldest domesticated cereal crops in Eurasia, but identifying foxtail millets, especially in charred grains, and differentiating it from its wild ancestor, green foxtail (Setaria viridis, in the archaeobotanical remains, is still problematic. Phytolithic analysis provides a meaningful method for identifying this important crop. In this paper, the silicon structure patterns in the glumes, lemmas, and paleas from inflorescence bracts in 16 modern plants of foxtail millet and green foxtail from China and Europe are examined using light microscopy with phase-contrast and a microscopic interferometer. Our research shows that the silicon structure of ΩIII from upper lemmas and paleas in foxtail millet and green foxtail can be correspondingly divided into two groups. The size of ΩIII type phytolith of foxtail millet is bigger than that from green foxtail. Discriminant function analysis reveals that 78.4% of data on foxtail millet and 76.9% of data on green foxtail are correctly classified. This means certain morphotypes of phytoliths are relatively reliable tools for distinguishing foxtail millet from green foxtail. Our results also revealed that the husk phytolith morphologies of foxtail millets from China and Eastern Europe are markedly different from those from Western Europe. Our research gives a meaningful method of separating foxtail millet and green foxtail. The implications of these findings for understanding the history of foxtail millet domestication and cultivation in ancient civilizations are significant.

  8. Differential Geometry

    CERN Document Server

    Stoker, J J

    2011-01-01

    This classic work is now available in an unabridged paperback edition. Stoker makes this fertile branch of mathematics accessible to the nonspecialist by the use of three different notations: vector algebra and calculus, tensor calculus, and the notation devised by Cartan, which employs invariant differential forms as elements in an algebra due to Grassman, combined with an operation called exterior differentiation. Assumed are a passing acquaintance with linear algebra and the basic elements of analysis.

  9. Integrated Transcriptomic and Epigenomic Analysis of Primary Human Lung Epithelial Cell Differentiation

    Science.gov (United States)

    Marconett, Crystal N.; Zhou, Beiyun; Rieger, Megan E.; Selamat, Suhaida A.; Dubourd, Mickael; Fang, Xiaohui; Lynch, Sean K.; Stueve, Theresa Ryan; Siegmund, Kimberly D.; Berman, Benjamin P.

    2013-01-01

    Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation. PMID:23818859

  10. Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects.

    Science.gov (United States)

    Dresch, Jacqueline M; Liu, Xiaozhou; Arnosti, David N; Ay, Ahmet

    2010-10-24

    Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context. We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity. Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary

  11. Cyber-T web server: differential analysis of high-throughput data.

    Science.gov (United States)

    Kayala, Matthew A; Baldi, Pierre

    2012-07-01

    The Bayesian regularization method for high-throughput differential analysis, described in Baldi and Long (A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 2001: 17: 509-519) and implemented in the Cyber-T web server, is one of the most widely validated. Cyber-T implements a t-test using a Bayesian framework to compute a regularized variance of the measurements associated with each probe under each condition. This regularized estimate is derived by flexibly combining the empirical measurements with a prior, or background, derived from pooling measurements associated with probes in the same neighborhood. This approach flexibly addresses problems associated with low replication levels and technology biases, not only for DNA microarrays, but also for other technologies, such as protein arrays, quantitative mass spectrometry and next-generation sequencing (RNA-seq). Here we present an update to the Cyber-T web server, incorporating several useful new additions and improvements. Several preprocessing data normalization options including logarithmic and (Variance Stabilizing Normalization) VSN transforms are included. To augment two-sample t-tests, a one-way analysis of variance is implemented. Several methods for multiple tests correction, including standard frequentist methods and a probabilistic mixture model treatment, are available. Diagnostic plots allow visual assessment of the results. The web server provides comprehensive documentation and example data sets. The Cyber-T web server, with R source code and data sets, is publicly available at http://cybert.ics.uci.edu/.

  12. Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil.

    Science.gov (United States)

    Leal, Mariana Ferreira; Chung, Janete; Calcagno, Danielle Queiroz; Assumpção, Paulo Pimentel; Demachki, Samia; da Silva, Ismael Dale Cotrim Guerreiro; Chammas, Roger; Burbano, Rommel Rodríguez; de Arruda Cardoso Smith, Marília

    2012-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in larger clinical study

  13. Landslide Kinematical Analysis through Inverse Numerical Modelling and Differential SAR Interferometry

    Science.gov (United States)

    Castaldo, R.; Tizzani, P.; Lollino, P.; Calò, F.; Ardizzone, F.; Lanari, R.; Guzzetti, F.; Manunta, M.

    2015-11-01

    The aim of this paper is to propose a methodology to perform inverse numerical modelling of slow landslides that combines the potentialities of both numerical approaches and well-known remote-sensing satellite techniques. In particular, through an optimization procedure based on a genetic algorithm, we minimize, with respect to a proper penalty function, the difference between the modelled displacement field and differential synthetic aperture radar interferometry (DInSAR) deformation time series. The proposed methodology allows us to automatically search for the physical parameters that characterize the landslide behaviour. To validate the presented approach, we focus our analysis on the slow Ivancich landslide (Assisi, central Italy). The kinematical evolution of the unstable slope is investigated via long-term DInSAR analysis, by exploiting about 20 years of ERS-1/2 and ENVISAT satellite acquisitions. The landslide is driven by the presence of a shear band, whose behaviour is simulated through a two-dimensional time-dependent finite element model, in two different physical scenarios, i.e. Newtonian viscous flow and a deviatoric creep model. Comparison between the model results and DInSAR measurements reveals that the deviatoric creep model is more suitable to describe the kinematical evolution of the landslide. This finding is also confirmed by comparing the model results with the available independent inclinometer measurements. Our analysis emphasizes that integration of different data, within inverse numerical models, allows deep investigation of the kinematical behaviour of slow active landslides and discrimination of the driving forces that govern their deformation processes.

  14. Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil.

    Directory of Open Access Journals (Sweden)

    Mariana Ferreira Leal

    Full Text Available Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in

  15. Differential proteome analysis of human embryonic kidney cell line (HEK-293 following mycophenolic acid treatment

    Directory of Open Access Journals (Sweden)

    Rahman Hazir

    2011-09-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as a post transplantation medicine to prevent acute organ rejection. In the present study we used proteomics approach to identify proteome alterations in human embryonic kidney cells (HEK-293 after treatment with therapeutic dose of MPA. Following 72 hours MPA treatment, total protein lysates were prepared, resolved by two dimensional gel electrophoresis and differentially expressed proteins were identified by QTOF-MS/MS analysis. Expressional regulations of selected proteins were further validated by real time PCR and Western blotting. Results The proliferation assay demonstrated that therapeutic MPA concentration causes a dose dependent inhibition of HEK-293 cell proliferation. A significant apoptosis was observed after MPA treatment, as revealed by caspase 3 activity. Proteome analysis showed a total of 12 protein spots exhibiting differential expression after incubation with MPA, of which 7 proteins (complement component 1 Q subcomponent-binding protein, electron transfer flavoprotein subunit beta, cytochrome b-c1 complex subunit, peroxiredoxin 1, thioredoxin domain-containing protein 12, myosin regulatory light chain 2, and profilin 1 showed significant increase in their expression. The expression of 5 proteins (protein SET, stathmin, 40S ribosomal protein S12, histone H2B type 1 A, and histone H2B type 1-C/E/F/G/I were down-regulated. MPA mainly altered the proteins associated with the cytoskeleton (26%, chromatin structure/dynamics (17% and energy production/conversion (17%. Both real time PCR and Western blotting confirmed the regulation of myosin regulatory light chain 2 and peroxiredoxin 1 by MPA treatment. Furthermore, HT-29 cells treated with MPA and total kidney cell lysate from MMF treated rats showed similar increased expression of myosin regulatory light chain 2. Conclusion The emerging use of MPA in diverse pathophysiological conditions demands in-depth studies to

  16. Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    Directory of Open Access Journals (Sweden)

    Jia W

    2016-08-01

    Full Text Available Wei Jia,1 Wei Wang,1 Chu-shu Ji,1 Jun-yang Niu,2 Ya-jing Lv,1 Hang-cheng Zhou,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Background: Both periostin (PN and epidermal growth factor receptor (EGFR can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS and overall survival (OS. Results: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044, differentiation grade (P=0.003, venous invasion (P=0.010, invasion depth (P=0.007, lymphatic metastasis (P=0.000, and tumor stage (P=0.000. The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000, invasion depth (P=0.022, and tumor stage (P=0.000. Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000 and DFS (P=0.000, which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS

  17. Sample size calculation while controlling false discovery rate for differential expression analysis with RNA-sequencing experiments.

    Science.gov (United States)

    Bi, Ran; Liu, Peng

    2016-03-31

    RNA-Sequencing (RNA-seq) experiments have been popularly applied to transcriptome studies in recent years. Such experiments are still relatively costly. As a result, RNA-seq experiments often employ a small number of replicates. Power analysis and sample size calculation are challenging in the context of differential expression analysis with RNA-seq data. One challenge is that there are no closed-form formulae to calculate power for the popularly applied tests for differential expression analysis. In addition, false discovery rate (FDR), instead of family-wise type I error rate, is controlled for the multiple testing error in RNA-seq data analysis. So far, there are very few proposals on sample size calculation for RNA-seq experiments. In this paper, we propose a procedure for sample size calculation while controlling FDR for RNA-seq experimental design. Our procedure is based on the weighted linear model analysis facilitated by the voom method which has been shown to have competitive performance in terms of power and FDR control for RNA-seq differential expression analysis. We derive a method that approximates the average power across the differentially expressed genes, and then calculate the sample size to achieve a desired average power while controlling FDR. Simulation results demonstrate that the actual power of several popularly applied tests for differential expression is achieved and is close to the desired power for RNA-seq data with sample size calculated based on our method. Our proposed method provides an efficient algorithm to calculate sample size while controlling FDR for RNA-seq experimental design. We also provide an R package ssizeRNA that implements our proposed method and can be downloaded from the Comprehensive R Archive Network ( http://cran.r-project.org ).

  18. Differential proteomics analysis to identify proteins and pathways associated with male sterility of soybean using iTRAQ-based strategy.

    Science.gov (United States)

    Li, Jiajia; Ding, Xianlong; Han, Shaohuai; He, Tingting; Zhang, Hao; Yang, Longshu; Yang, Shouping; Gai, Junyi

    2016-04-14

    To further elucidate the molecular mechanism of cytoplasmic male sterility (CMS) in soybean, a differential proteomic analysis was completed between the CMS line NJCMS1A and its maintainer NJCMS1B using iTRAQ-based strategy. As a result, 180 differential abundance proteins (DAPs) were identified, of which, 60 were down-regulated and 120 were up-regulated in NJCMS1A compared with NJCMS1B. Bioinformatic analysis showed that 167 DAPs were annotated in 41 Gene Ontology functional groups, 106 DAPs were classified into 20 clusters of orthologous groups of protein categories, and 128 DAPs were enrichment in 53 KEGG pathways. Fifteen differential level proteins/genes with the same expression pattern were identified in the further conjoint analysis of DAPs and the previously reported differential expression genes. Moreover, multiple reaction monitoring test, qRT-PCR analysis and enzyme activity assay validated that the iTRAQ results were reliable. Based on functional analysis of DAPs, we concluded that male sterility in NJCMS1A might be related to insufficiencies in energy supply, unbalance of protein synthesis and degradation, disruption of flavonoid synthesis, programmed cell death, abnormalities of substance metabolism, etc. These results might facilitate our understanding of the molecular mechanisms behind CMS in soybean. Soybean is an important global crop that provides protein and oil. Heterosis is a significantly potential approach to increase the yield of soybean. Cytoplasmic male sterility (CMS) plays a vital role in the production of hybrid seeds. However, the genetic and molecular mechanisms of male sterility in soybean still need to be further elucidated. In the present paper, a differential proteomic analysis was carried out and the results showed that several key proteins involved in key pathways were associated with male sterility in soybean. This work provides a new insight to understand the genetic and molecular mechanisms underlying CMS in soybean

  19. Dimensional analysis to transform the differential equations in partial derivates in the theory of heat transmission into ordinary ones

    International Nuclear Information System (INIS)

    Diaz Sanchidrian, C.

    1989-01-01

    The present paper applies dimensional analysis with spatial discrimination to transform the differential equations in partial derivatives developed in the theory of heat transmission into ordinary ones. The effectivity of the method is comparable to that methods based in transformations of uni or multiparametric groups, with the advantage of being more direct and simple. (Author)

  20. Teacher Implementation of Trial-Based Functional Analysis and Differential Reinforcement of Alternative Behavior for Students with Challenging Behavior

    Science.gov (United States)

    Flynn, Susan D.; Lo, Ya-yu

    2016-01-01

    The purpose of this study was to examine the effects of a training package on three middle school special education teachers' accurate implementation of trial-based functional analysis (TBFA) and differential reinforcement of alternative behavior (DRA) with their students with autism spectrum disorders or emotional and behavioral disorders in the…

  1. Application of the Lie Symmetry Analysis for second-order fractional differential equations

    Directory of Open Access Journals (Sweden)

    Mousa Ilie

    2017-12-01

    Full Text Available Obtaining analytical or numerical solution of fractional differential equations is one of the troublesome and challenging issue among mathematicians and engineers, specifically in recent years. The purpose of this paper Lie Symmetry method is developed to solve second-order fractional differential equations, based on conformable fractional derivative. Some numerical examples are presented to illustrate the proposed approach.

  2. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation

    NARCIS (Netherlands)

    Bogaard, E.H. van den; Podolsky, M.A.; Smits, J.P.H.; Cui, X.; John, C.; Gowda, K.; Desai, D.; Amin, S.G.; Schalkwijk, J.; Perdew, G.H.; Glick, A.B.

    2015-01-01

    Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis

  3. Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution.

    Science.gov (United States)

    Kumar, Narender; Mariappan, Vanitha; Baddam, Ramani; Lankapalli, Aditya K; Shaik, Sabiha; Goh, Khean-Lee; Loke, Mun Fai; Perkins, Tim; Benghezal, Mohammed; Hasnain, Seyed E; Vadivelu, Jamuna; Marshall, Barry J; Ahmed, Niyaz

    2015-01-01

    The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Nonlinear dynamics analysis of a low-temperature-differential kinematic Stirling heat engine

    Science.gov (United States)

    Izumida, Yuki

    2018-03-01

    The low-temperature-differential (LTD) Stirling heat engine technology constitutes one of the important sustainable energy technologies. The basic question of how the rotational motion of the LTD Stirling heat engine is maintained or lost based on the temperature difference is thus a practically and physically important problem that needs to be clearly understood. Here, we approach this problem by proposing and investigating a minimal nonlinear dynamic model of an LTD kinematic Stirling heat engine. Our model is described as a driven nonlinear pendulum where the motive force is the temperature difference. The rotational state and the stationary state of the engine are described as a stable limit cycle and a stable fixed point of the dynamical equations, respectively. These two states coexist under a sufficient temperature difference, whereas the stable limit cycle does not exist under a temperature difference that is too small. Using a nonlinear bifurcation analysis, we show that the disappearance of the stable limit cycle occurs via a homoclinic bifurcation, with the temperature difference being the bifurcation parameter.

  5. Differential Fault Analysis on CLEFIA with 128, 192, and 256-Bit Keys

    Science.gov (United States)

    Takahashi, Junko; Fukunaga, Toshinori

    This paper describes a differential fault analysis (DFA) attack against CLEFIA. The proposed attack can be applied to CLEFIA with all supported keys: 128, 192, and 256-bit keys. DFA is a type of side-channel attack. This attack enables the recovery of secret keys by injecting faults into a secure device during its computation of the cryptographic algorithm and comparing the correct ciphertext with the faulty one. CLEFIA is a 128-bit blockcipher with 128, 192, and 256-bit keys developed by the Sony Corporation in 2007. CLEFIA employs a generalized Feistel structure with four data lines. We developed a new attack method that uses this characteristic structure of the CLEFIA algorithm. On the basis of the proposed attack, only 2 pairs of correct and faulty ciphertexts are needed to retrieve the 128-bit key, and 10.78 pairs on average are needed to retrieve the 192 and 256-bit keys. The proposed attack is more efficient than any previously reported. In order to verify the proposed attack and estimate the calculation time to recover the secret key, we conducted an attack simulation using a PC. The simulation results show that we can obtain each secret key within three minutes on average. This result shows that we can obtain the entire key within a feasible computational time.

  6. Physical activity interventions differentially affect exercise task and barrier self-efficacy: a meta-analysis.

    Science.gov (United States)

    Higgins, Torrance J; Middleton, Kathryn R; Winner, Larry; Janelle, Christopher M

    2014-08-01

    Researchers have yet to establish how interventions to increase physical activity influence specific self-efficacy beliefs. The current study sought to quantify the effect of interventions to increase physical activity among healthy adults on exercise task (EXSE) and barrier self-efficacy (BSE) via meta-analysis. Intervention characteristics associated with self-efficacy and physical activity changes were also identified. A systematic database search and manual searches through reference lists of related publications were conducted for articles on randomized, controlled physical activity interventions. Published intervention studies reporting changes in physical activity behavior and either EXSE or BSE in healthy adults were eligible for inclusion. Of the 1,080 studies identified, 20 were included in the meta-analyses. Interventions had a significant effect of g = 0.208, 95% confidence interval (CI) [0.027, 0.388], p exercise sessions effectively increased EXSE and physical activity, whereas long interventions improved BSE. Interventions that did not provide support increased BSE and physical activity levels. Further, interventions that did not require the use of daily exercise logs improved EXSE and physical activity behavior. Interventions designed to increase physical activity differentially influenced EXSE and BSE. EXSE appeared to play a more significant role during exercise adoption, whereas BSE was involved in the maintenance of exercise behavior. Recommendations are offered for the design of future interventions.

  7. PHARMACEUTICAL AMORPHOUS ORGANIC MATERIALS CHARACTERIZATION BY USING THE DIFFERENTIAL SCANNING CALORIMETRY AND DYNAMIC MECHANICAL ANALYSIS

    Directory of Open Access Journals (Sweden)

    Ion Dranca

    2011-12-01

    Full Text Available This research has been carried out in order to demonstrate the use of differential scanning calorimetry (DSC in detecting and measuring α- and β-relaxation processes in amorphous pharmaceutical systems. DSC has been employed to study amorphous samples of poly (vinylpyrrolidone (PVP, indomethacin (InM, and ursodeoxycholic acid (UDA that are annealed at temperature (Ta around 0.8 of their glass transition temperature (Tg. Dynamic mechanical analysis (DMA is used to measure β- relaxation in PVP. Yet, the DSC has been used to study the glassy indomethacin aged at 0 and -10 oC for periods of time up to 109 and 210 days respectively. The results demonstrate the emergence of a small melting peak of the α-polymorph after aging for 69 days at 0°C and for 147 days at -10°C (i.e., ~55°C below the glass transition temperature that provides evidence of nucleation occurring in the temperature region of the β-relaxation.

  8. On the limits of probabilistic forecasting in nonlinear time series analysis II: Differential entropy.

    Science.gov (United States)

    Amigó, José M; Hirata, Yoshito; Aihara, Kazuyuki

    2017-08-01

    In a previous paper, the authors studied the limits of probabilistic prediction in nonlinear time series analysis in a perfect model scenario, i.e., in the ideal case that the uncertainty of an otherwise deterministic model is due to only the finite precision of the observations. The model consisted of the symbolic dynamics of a measure-preserving transformation with respect to a finite partition of the state space, and the quality of the predictions was measured by the so-called ignorance score, which is a conditional entropy. In practice, though, partitions are dispensed with by considering numerical and experimental data to be continuous, which prompts us to trade off in this paper the Shannon entropy for the differential entropy. Despite technical differences, we show that the core of the previous results also hold in this extended scenario for sufficiently high precision. The corresponding imperfect model scenario will be revisited too because it is relevant for the applications. The theoretical part and its application to probabilistic forecasting are illustrated with numerical simulations and a new prediction algorithm.

  9. Analysis of vineyard differential management zones and relation to vine development, grape maturity and quality

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Casanovas, J. A.; Agelet-Fernandez, J.; Arno, J.; Ramos, M. C.

    2012-11-01

    The objective of research was to analyse the potential of Normalized Difference Vegetation Index (NDVI) maps from satellite images, yield maps and grapevine fertility and load variables to delineate zones with different wine grape properties for selective harvesting. Two vineyard blocks located in NE Spain (Cabernet Sauvignon and Syrah) were analysed. The NDVI was computed from a Quickbird-2 multi-spectral image at veraison (July 2005). Yield data was acquired by means of a yield monitor during September 2005. Other variables, such as the number of buds, number of shoots, number of wine grape clusters and weight of 100 berries were sampled in a 10 rows × 5 vines pattern and used as input variables, in combination with the NDVI, to define the clusters as alternative to yield maps. Two days prior to the harvesting, grape samples were taken. The analysed variables were probable alcoholic degree, pH of the juice, total acidity, total phenolics, colour, anthocyanins and tannins. The input variables, alone or in combination, were clustered (2 and 3 Clusters) by using the ISODATA algorithm, and an analysis of variance and a multiple rang test were performed. The results show that the zones derived from the NDVI maps are more effective to differentiate grape maturity and quality variables than the zones derived from the yield maps. The inclusion of other grapevine fertility and load variables did not improve the results. (Author) 36 refs.

  10. Improving differential die-away analysis via the use of neutron poisons in detectors

    International Nuclear Information System (INIS)

    Jordan, Kelly A.; Vujic, Jasmina; Phillips, Emmanuel; Gozani, Tsahi

    2007-01-01

    Differential Die-Away Analysis (DDAA) is an active interrogation technique to detect special nuclear material (SNM). In DDAA, a pulsed neutron generator produces pulses of neutrons that are directed into a cargo to be interrogated. As each pulse passes through the cargo, the neutrons are thermalized and absorbed. If SNM is present, the thermalized neutrons from the source will cause fissions that produce a new source of neutrons. The number of thermal neutrons decay exponentially with the diffusion decay time of the inspected medium, on the order of hundreds of μs. An external neutron detector which is designed to detect only epithermal neutrons, will measure only a single decaying exponential when there is no SNM present, and two exponentials when SNM is present. This paper shows that in many cases, a gain in detection sensitivity can be realized by introducing a thermal neutron poison (such as boron) into the detector. This poison will reduce the efficiency of the detector, but decrease its decay time. A decreased decay time will cause the separation between the detector and fission signal exponentials to occur at an earlier time. There is a balance between efficiency and time constant for a detector. The boron concentration to achieve the maximum sensitivity, and its magnitude, will be different for different detector designs

  11. Genetic analysis of the resistance to eight anthracnose races in the common bean differential cultivar Kaboon.

    Science.gov (United States)

    Campa, Ana; Giraldez, Ramón; Ferreira, Juan José

    2011-06-01

    Resistance to the eight races (3, 7, 19, 31, 81, 449, 453, and 1545) of the pathogenic fungus Colletotrichum lindemuthianum (anthracnose) was evaluated in F(3) families derived from the cross between the anthracnose differential bean cultivars Kaboon and Michelite. Molecular marker analyses were carried out in the F(2) individuals in order to map and characterize the anthracnose resistance genes or gene clusters present in Kaboon. The analysis of the combined segregations indicates that the resistance present in Kaboon against these eight anthracnose races is determined by 13 different race-specific genes grouped in three clusters. One of these clusters, corresponding to locus Co-1 in linkage group (LG) 1, carries two dominant genes conferring specific resistance to races 81 and 1545, respectively, and a gene necessary (dominant complementary gene) for the specific resistance to race 31. A second cluster, corresponding to locus Co-3/9 in LG 4, carries six dominant genes conferring specific resistance to races 3, 7, 19, 449, 453, and 1545, respectively, and the second dominant complementary gene for the specific resistance to race 31. A third cluster of unknown location carries three dominant genes conferring specific resistance to races 449, 453, and 1545, respectively. This is the first time that two anthracnose resistance genes with a complementary mode of action have been mapped in common bean and their relationship with previously known Co- resistance genes established.

  12. A novel flow-based strategy for implementing differential kinetic analysis

    International Nuclear Information System (INIS)

    Fortes, Paula R.; Meneses, Silvia R.P.; Zagatto, Elias A.G.

    2006-01-01

    Differential kinetic analysis can be implemented in a multi-pumping flow system, and this was demonstrated in relation to an improved spectrophotometric catalytic determination of iron and vanadium in Fe-V alloys. The method exploited the influence of Fe(II) and V(IV) on the rate of iodide oxidation by Cr(VI) under acidic conditions; therefore the Jones reductor was needed. The sample was inserted into an acidic KI stream that acted also as carrier stream, and a Cr(VI) solution was added by confluence. Successive measurements were performed during sample passage through the detector, each one related to a different yet reproducible condition for reaction development. Data treatment involved multivariate calibration by the PLS algorithm. The proposed system is very simple and rugged, allowing about 50 samples to be run per hour, meaning 48 mg KI per determination. The first two latent variables carry ca. 94% of the analytical information, pointing out that the intrinsic dimensionality of the data set is two. Results are in agreement with inductively coupled argon plasma-optical emission spectrometry

  13. Physical activity interventions differentially affect exercise task and barrier self-efficacy: A meta-analysis

    Science.gov (United States)

    Higgins, Torrance J.; Middleton, Kathryn R.; Winner, Larry; Janelle, Christopher M.; Middleton, Kathryn R.

    2014-01-01

    Objective Researchers have yet to establish how interventions to increase physical activity influence specific self-efficacy beliefs. The current study sought to quantify the effect of interventions to increase physical activity among healthy adults on exercise task (EXSE) and barrier self-efficacy (BSE) via meta-analysis. Intervention characteristics associated with self-efficacy and physical activity changes were also identified. Methods A systematic database search and manual searches through reference lists of related publications were conducted for articles on randomized, controlled physical activity interventions. Published intervention studies reporting changes in physical activity behavior and either EXSE or BSE in healthy adults were eligible for inclusion. Results Of the 1,080 studies identified, 20 were included in the meta-analyses. Interventions had a significant effect of g = 0.208, 95% confidence interval (CI) [0.027, 0.388], p physical activity. Moderator analyses indicated shorter interventions that did not include structured exercise sessions effectively increased EXSE and physical activity, whereas long interventions improved BSE. Interventions that did not provide support increased BSE and physical activity levels. Further, interventions that did not require the use of daily exercise logs improved EXSE and physical activity behavior. Conclusion Interventions designed to increase physical activity differentially influenced EXSE and BSE. EXSE appeared to play a more significant role during exercise adoption, whereas BSE was involved in the maintenance of exercise behavior. Recommendations are offered for the design of future interventions. PMID:23957904

  14. Partial differential equation-based approach for empirical mode decomposition: application on image analysis.

    Science.gov (United States)

    Niang, Oumar; Thioune, Abdoulaye; El Gueirea, Mouhamed Cheikh; Deléchelle, Eric; Lemoine, Jacques

    2012-09-01

    The major problem with the empirical mode decomposition (EMD) algorithm is its lack of a theoretical framework. So, it is difficult to characterize and evaluate this approach. In this paper, we propose, in the 2-D case, the use of an alternative implementation to the algorithmic definition of the so-called "sifting process" used in the original Huang's EMD method. This approach, especially based on partial differential equations (PDEs), was presented by Niang in previous works, in 2005 and 2007, and relies on a nonlinear diffusion-based filtering process to solve the mean envelope estimation problem. In the 1-D case, the efficiency of the PDE-based method, compared to the original EMD algorithmic version, was also illustrated in a recent paper. Recently, several 2-D extensions of the EMD method have been proposed. Despite some effort, 2-D versions for EMD appear poorly performing and are very time consuming. So in this paper, an extension to the 2-D space of the PDE-based approach is extensively described. This approach has been applied in cases of both signal and image decomposition. The obtained results confirm the usefulness of the new PDE-based sifting process for the decomposition of various kinds of data. Some results have been provided in the case of image decomposition. The effectiveness of the approach encourages its use in a number of signal and image applications such as denoising, detrending, or texture analysis.

  15. Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

    Science.gov (United States)

    Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

    2014-03-01

    This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

  16. Genetic differentiation and origin of the Jordanian population: an analysis of Alu insertion polymorphisms.

    Science.gov (United States)

    Bahri, Raoudha; El Moncer, Wifak; Al-Batayneh, Khalid; Sadiq, May; Esteban, Esther; Moral, Pedro; Chaabani, Hassen

    2012-05-01

    Although much of Jordan is covered by desert, its north-western region forms part of the Fertile Crescent region that had given a rich past to Jordanians. This past, scarcely described by historians, is not yet clarified by sufficient genetic data. Thus in this paper we aim to determine the genetic differentiation of the Jordanian population and to discuss its origin. A total of 150 unrelated healthy Jordanians were investigated for ten Alu insertion polymorphisms. Genetic relationships among populations were estimated by a principal component (PC) plot based on the analyses of the R-matrix software. Statistical analysis showed that the Jordanian population is not significantly different from the United Arab Emirates population or the North Africans. This observation, well represented in PC plot, suggests a common origin of these populations belonging respectively to ancient Mesopotamia, Arabia, and North Africa. Our results are compatible with ancient peoples' movements from Arabia to ancient Mesopotamia and North Africa as proposed by historians and supported by previous genetic results. The original genetic profile of the Jordanian population, very likely Arabian Semitic, has not been subject to significant change despite the succession of several civilizations.

  17. Gravimetric analysis and differential scanning calorimetric studies on glycerin-induced skin hydration.

    Science.gov (United States)

    Lee, Ae-Ri Cho; Moon, Hee Kyung

    2007-11-01

    A thermal gravimetric analysis (TGA) and a differential scanning calorimetry (DSC) were carried out to characterize the water property and an alteration of lipid phase transition of stratum corneum (SC) by glycerin. In addition, the relationship between steady state skin permeation rate and skin hydration in various concentrations of glycerin was investigated. Water vapor absorption-desorption was studied in the hairless mouse stratum corneum. Dry SC samples were exposed to different conc. of glycerin (0-50%) followed by exposure to dry air and the change in weight property was monitored over time by use of TGA. In DSC study, significant decrease in DeltaH of the lipid transition in 10% glycerin and water treated sample: the heat of lipid transition of normal, water, 10% glycerin treated SC were 6.058, 4.412 and 4.316 mJ/mg, respectively. In 10% glycerin treated SCs, the Tc of water shifts around 129 degrees C, corresponding to the weakly bound secondary water. In 40% glycerin treated SC, the Tc of water shifts to 144 degrees C corresponding to strongly bound primary water. There was a good correlation between the hydration property of the skin and the steady state skin flux with the correlation coefficient (r2=0.94). As the hydration increased, the steady state flux increased. As glycerin concentration increased, hydration property decreased. High diffusivity induced by the hydration effect of glycerin and water could be the major contributing factor for the enhanced skin permeation of nicotinic acid (NA).

  18. Proteomic analysis identifies differentially expressed proteins after red propolis treatment in Hep-2 cells.

    Science.gov (United States)

    Frozza, Caroline Olivieri da Silva; Ribeiro, Tanara da Silva; Gambato, Gabriela; Menti, Caroline; Moura, Sidnei; Pinto, Paulo Marcos; Staats, Charley Christian; Padilha, Francine Ferreira; Begnini, Karine Rech; de Leon, Priscila Marques Moura; Borsuk, Sibele; Savegnago, Lucielli; Dellagostin, Odir; Collares, Tiago; Seixas, Fabiana Kömmling; Henriques, João Antonio Pêgas; Roesch-Ely, Mariana

    2014-01-01

    Here we investigated alterations in the protein profile of Hep-2 treated with red propolis using two-dimensional electrophoresis associated to mass spectrometry and apoptotic rates of cells treated with and without red propolis extracts through TUNEL and Annexin-V assays. A total of 325 spots were manually excised from the two-dimensional gel electrophoresis and 177 proteins were identified using LC-MS-MS. Among all proteins identified that presented differential expression, most were down-regulated in presence of red propolis extract at a concentration of 120 μg/mL (IC50): GRP78, PRDX2, LDHB, VIM and TUBA1A. Only two up-regulated proteins were identified in this study in the non-cytotoxic (6 μg/mL) red propolis treated group: RPLP0 and RAD23B. TUNEL staining assay showed a markedly increase in the mid- to late-stage apoptosis of Hep-2 cells induced by red propolis at concentrations of 60 and 120 μg/mL when compared with non-treated cells. The increase of late apoptosis was confirmed by in situ Annexin-V analysis in which red propolis extract induced late apoptosis in a dose-dependent manner. The differences in tumor cell protein profiles warrant further investigations including isolation of major bioactive compounds of red propolis in different cell lines using proteomics and molecular tests to validate the protein expression here observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Proteome analysis of functionally differentiated bovine (Bos indicus) mammary epithelial cells isolated from milk

    KAUST Repository

    Janjanam, Jagadeesh

    2013-10-01

    Mammary gland is made up of a branching network of ducts that end in alveoli. Terminally differentiated mammary epithelial cells (MECs) constitute the innermost layer of aveoli. They are milk-secreting cuboidal cells that secrete milk proteins during lactation. Little is known about the expression profile of proteins in the metabolically active MECs during lactation or their functional role in the lactation process. In the present investigation, we have reported the proteome map of MECs in lactating cows using 2DE MALDI-TOF/TOF MS and 1D-Gel-LC-MS/MS. MECs were isolated from milk using immunomagnetic beads and confirmed by RT-PCR and Western blotting. The 1D-Gel-LC-MS/MS and 2DE-MS/MS based approaches led to identification of 431 and 134 proteins, respectively, with a total of 497 unique proteins. Proteins identified in this study were clustered into functional groups using bioinformatics tools. Pathway analysis of the identified proteins revealed 28 pathways (p < 0.05) providing evidence for involvement of various proteins in lactation function. This study further provides experimental evidence for the presence of many proteins that have been predicted in annotated bovine genome. The data generated further provide a set of bovine MEC-specific proteins that will help the researchers to understand the molecular events taking place during lactation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Computer-aided analysis of CT images for the differentiation of cerebral tumors

    International Nuclear Information System (INIS)

    Michalik, M.; Michalik, S.; Bornholdt, F.

    1988-01-01

    For the integration of CT imaging into the differential diagnostics of intracranial space occupations, the selection and description of characteristics facilitating a good discrimination of serveral classes of tumors becomes a very important task. From images of 93 patients with the most frequent brain tumors the optimal set of characteristics was determined. The four most significant characteristics for the differentiation of brain tumors are 'uptake of contrast medium by the tumor', 'deliniation of the tumor contours', 'progression of the tumor' and the 'average tumor density after administration of contrast media'. Very good results were obtained for the differentiation of menigneomas with and without anaplasia and for the differentiation of meningeomas from all other tumors examined. The differentiation of the degree of malignancy for various gliomatous tumors was difficult. An accurate reclassification with the computer program was obtained for 83.4% of all tumors. (author)