WorldWideScience

Sample records for evidence-ranked motif identification

  1. Pipeline for the Analysis of ChIP-seq Data and New Motif Ranking Procedure

    KAUST Repository

    Ashoor, Haitham

    2011-06-01

    This thesis presents a computational methodology for ab-initio identification of transcription factor binding sites based on ChIP-seq data. This method consists of three main steps, namely ChIP-seq data processing, motif discovery and models selection. A novel method for ranking the models of motifs identified in this process is proposed. This method combines multiple factors in order to rank the provided candidate motifs. It combines the model coverage of the ChIP-seq fragments that contain motifs from which that model is built, the suitable background data made up of shuffled ChIP-seq fragments, and the p-value that resulted from evaluating the model on actual and background data. Two ChIP-seq datasets retrieved from ENCODE project are used to evaluate and demonstrate the ability of the method to predict correct TFBSs with high precision. The first dataset relates to neuron-restrictive silencer factor, NRSF, while the second one corresponds to growth-associated binding protein, GABP. The pipeline system shows high precision prediction for both datasets, as in both cases the top ranked motif closely resembles the known motifs for the respective transcription factors.

  2. Motif discovery in ranked lists of sequences

    DEFF Research Database (Denmark)

    Nielsen, Morten Muhlig; Tataru, Paula; Madsen, Tobias

    2016-01-01

    Motif analysis has long been an important method to characterize biological functionality and the current growth of sequencing-based genomics experiments further extends its potential. These diverse experiments often generate sequence lists ranked by some functional property. There is therefore...... advantage of the regular expression feature, including enrichments for combinations of different microRNA seed sites. The method is implemented and made publicly available as an R package and supports high parallelization on multi-core machinery....... a growing need for motif analysis methods that can exploit this coupled data structure and be tailored for specific biological questions. Here, we present an exploratory motif analysis tool, Regmex (REGular expression Motif EXplorer), which offers several methods to evaluate the correlation of motifs...

  3. MotifMark: Finding regulatory motifs in DNA sequences.

    Science.gov (United States)

    Hassanzadeh, Hamid Reza; Kolhe, Pushkar; Isbell, Charles L; Wang, May D

    2017-07-01

    The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity between proteins and DNA motifs. Despite their success, these technologies have their own limitations and fall short in precise characterization of motifs, and as a result, require further downstream analysis to extract useful and interpretable information from a haystack of noisy and inaccurate data. Here we propose MotifMark, a new algorithm based on graph theory and machine learning, that can find binding sites on candidate probes and rank their specificity in regard to the underlying transcription factor. We developed a pipeline to analyze experimental data derived from compact universal protein binding microarrays and benchmarked it against two of the most accurate motif search methods. Our results indicate that MotifMark can be a viable alternative technique for prediction of motif from protein binding microarrays and possibly other related high-throughput techniques.

  4. The identification of functional motifs in temporal gene expression analysis

    Directory of Open Access Journals (Sweden)

    Michael G. Surette

    2005-01-01

    Full Text Available The identification of transcription factor binding sites is essential to the understanding of the regulation of gene expression and the reconstruction of genetic regulatory networks. The in silico identification of cis-regulatory motifs is challenging due to sequence variability and lack of sufficient data to generate consensus motifs that are of quantitative or even qualitative predictive value. To determine functional motifs in gene expression, we propose a strategy to adopt false discovery rate (FDR and estimate motif effects to evaluate combinatorial analysis of motif candidates and temporal gene expression data. The method decreases the number of predicted motifs, which can then be confirmed by genetic analysis. To assess the method we used simulated motif/expression data to evaluate parameters. We applied this approach to experimental data for a group of iron responsive genes in Salmonella typhimurium 14028S. The method identified known and potentially new ferric-uptake regulator (Fur binding sites. In addition, we identified uncharacterized functional motif candidates that correlated with specific patterns of expression. A SAS code for the simulation and analysis gene expression data is available from the first author upon request.

  5. DMINDA: an integrated web server for DNA motif identification and analyses.

    Science.gov (United States)

    Ma, Qin; Zhang, Hanyuan; Mao, Xizeng; Zhou, Chuan; Liu, Bingqiang; Chen, Xin; Xu, Ying

    2014-07-01

    DMINDA (DNA motif identification and analyses) is an integrated web server for DNA motif identification and analyses, which is accessible at http://csbl.bmb.uga.edu/DMINDA/. This web site is freely available to all users and there is no login requirement. This server provides a suite of cis-regulatory motif analysis functions on DNA sequences, which are important to elucidation of the mechanisms of transcriptional regulation: (i) de novo motif finding for a given set of promoter sequences along with statistical scores for the predicted motifs derived based on information extracted from a control set, (ii) scanning motif instances of a query motif in provided genomic sequences, (iii) motif comparison and clustering of identified motifs, and (iv) co-occurrence analyses of query motifs in given promoter sequences. The server is powered by a backend computer cluster with over 150 computing nodes, and is particularly useful for motif prediction and analyses in prokaryotic genomes. We believe that DMINDA, as a new and comprehensive web server for cis-regulatory motif finding and analyses, will benefit the genomic research community in general and prokaryotic genome researchers in particular. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Highly scalable Ab initio genomic motif identification

    KAUST Repository

    Marchand, Benoit; Bajic, Vladimir B.; Kaushik, Dinesh

    2011-01-01

    We present results of scaling an ab initio motif family identification system, Dragon Motif Finder (DMF), to 65,536 processor cores of IBM Blue Gene/P. DMF seeks groups of mutually similar polynucleotide patterns within a set of genomic sequences and builds various motif families from them. Such information is of relevance to many problems in life sciences. Prior attempts to scale such ab initio motif-finding algorithms achieved limited success. We solve the scalability issues using a combination of mixed-mode MPI-OpenMP parallel programming, master-slave work assignment, multi-level workload distribution, multi-level MPI collectives, and serial optimizations. While the scalability of our algorithm was excellent (94% parallel efficiency on 65,536 cores relative to 256 cores on a modest-size problem), the final speedup with respect to the original serial code exceeded 250,000 when serial optimizations are included. This enabled us to carry out many large-scale ab initio motiffinding simulations in a few hours while the original serial code would have needed decades of execution time. Copyright 2011 ACM.

  7. Cross-cultural differences in processing of architectural ranking: evidence from an event-related potential study.

    Science.gov (United States)

    Mecklinger, Axel; Kriukova, Olga; Mühlmann, Heiner; Grunwald, Thomas

    2014-01-01

    Visual object identification is modulated by perceptual experience. In a cross-cultural ERP study we investigated whether cultural expertise determines how buildings that vary in their ranking between high and low according to the Western architectural decorum are perceived. Two groups of German and Chinese participants performed an object classification task in which high- and low-ranking Western buildings had to be discriminated from everyday life objects. ERP results indicate that an early stage of visual object identification (i.e., object model selection) is facilitated for high-ranking buildings for the German participants, only. At a later stage of object identification, in which object knowledge is complemented by information from semantic and episodic long-term memory, no ERP evidence for cultural differences was obtained. These results suggest that the identification of architectural ranking is modulated by culturally specific expertise with Western-style architecture already at an early processing stage.

  8. Identification of helix capping and {beta}-turn motifs from NMR chemical shifts

    Energy Technology Data Exchange (ETDEWEB)

    Shen Yang; Bax, Ad, E-mail: bax@nih.gov [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

    2012-03-15

    We present an empirical method for identification of distinct structural motifs in proteins on the basis of experimentally determined backbone and {sup 13}C{sup {beta}} chemical shifts. Elements identified include the N-terminal and C-terminal helix capping motifs and five types of {beta}-turns: I, II, I Prime , II Prime and VIII. Using a database of proteins of known structure, the NMR chemical shifts, together with the PDB-extracted amino acid preference of the helix capping and {beta}-turn motifs are used as input data for training an artificial neural network algorithm, which outputs the statistical probability of finding each motif at any given position in the protein. The trained neural networks, contained in the MICS (motif identification from chemical shifts) program, also provide a confidence level for each of their predictions, and values ranging from ca 0.7-0.9 for the Matthews correlation coefficient of its predictions far exceed those attainable by sequence analysis. MICS is anticipated to be useful both in the conventional NMR structure determination process and for enhancing on-going efforts to determine protein structures solely on the basis of chemical shift information, where it can aid in identifying protein database fragments suitable for use in building such structures.

  9. Identification of helix capping and β-turn motifs from NMR chemical shifts

    International Nuclear Information System (INIS)

    Shen Yang; Bax, Ad

    2012-01-01

    We present an empirical method for identification of distinct structural motifs in proteins on the basis of experimentally determined backbone and 13 C β chemical shifts. Elements identified include the N-terminal and C-terminal helix capping motifs and five types of β-turns: I, II, I′, II′ and VIII. Using a database of proteins of known structure, the NMR chemical shifts, together with the PDB-extracted amino acid preference of the helix capping and β-turn motifs are used as input data for training an artificial neural network algorithm, which outputs the statistical probability of finding each motif at any given position in the protein. The trained neural networks, contained in the MICS (motif identification from chemical shifts) program, also provide a confidence level for each of their predictions, and values ranging from ca 0.7–0.9 for the Matthews correlation coefficient of its predictions far exceed those attainable by sequence analysis. MICS is anticipated to be useful both in the conventional NMR structure determination process and for enhancing on-going efforts to determine protein structures solely on the basis of chemical shift information, where it can aid in identifying protein database fragments suitable for use in building such structures.

  10. Identification of important nodes in directed biological networks: a network motif approach.

    Directory of Open Access Journals (Sweden)

    Pei Wang

    Full Text Available Identification of important nodes in complex networks has attracted an increasing attention over the last decade. Various measures have been proposed to characterize the importance of nodes in complex networks, such as the degree, betweenness and PageRank. Different measures consider different aspects of complex networks. Although there are numerous results reported on undirected complex networks, few results have been reported on directed biological networks. Based on network motifs and principal component analysis (PCA, this paper aims at introducing a new measure to characterize node importance in directed biological networks. Investigations on five real-world biological networks indicate that the proposed method can robustly identify actually important nodes in different networks, such as finding command interneurons, global regulators and non-hub but evolutionary conserved actually important nodes in biological networks. Receiver Operating Characteristic (ROC curves for the five networks indicate remarkable prediction accuracy of the proposed measure. The proposed index provides an alternative complex network metric. Potential implications of the related investigations include identifying network control and regulation targets, biological networks modeling and analysis, as well as networked medicine.

  11. An efficient identification strategy of clonal tea cultivars using long-core motif SSR markers.

    Science.gov (United States)

    Wang, Rang Jian; Gao, Xiang Feng; Kong, Xiang Rui; Yang, Jun

    2016-01-01

    Microsatellites, or simple sequence repeats (SSRs), especially those with long-core motifs (tri-, tetra-, penta-, and hexa-nucleotide) represent an excellent tool for DNA fingerprinting. SSRs with long-core motifs are preferred since neighbor alleles are more easily separated and identified from each other, which render the interpretation of electropherograms and the true alleles more reliable. In the present work, with the purpose of characterizing a set of core SSR markers with long-core motifs for well fingerprinting clonal cultivars of tea (Camellia sinensis), we analyzed 66 elite clonal tea cultivars in China with 33 initially-chosen long-core motif SSR markers covering all the 15 linkage groups of tea plant genome. A set of 6 SSR markers were conclusively selected as core SSR markers after further selection. The polymorphic information content (PIC) of the core SSR markers was >0.5, with ≤5 alleles in each marker containing 10 or fewer genotypes. Phylogenetic analysis revealed that the core SSR markers were not strongly correlated with the trait 'cultivar processing-property'. The combined probability of identity (PID) between two random cultivars for the whole set of 6 SSR markers was estimated to be 2.22 × 10(-5), which was quite low, confirmed the usefulness of the proposed SSR markers for fingerprinting analyses in Camellia sinensis. Moreover, for the sake of quickly discriminating the clonal tea cultivars, a cultivar identification diagram (CID) was subsequently established using these core markers, which fully reflected the identification process and provided the immediate information about which SSR markers were needed to identify a cultivar chosen among the tested ones. The results suggested that long-core motif SSR markers used in the investigation contributed to the accurate and efficient identification of the clonal tea cultivars and enabled the protection of intellectual property.

  12. BayesMotif: de novo protein sorting motif discovery from impure datasets.

    Science.gov (United States)

    Hu, Jianjun; Zhang, Fan

    2010-01-18

    Protein sorting is the process that newly synthesized proteins are transported to their target locations within or outside of the cell. This process is precisely regulated by protein sorting signals in different forms. A major category of sorting signals are amino acid sub-sequences usually located at the N-terminals or C-terminals of protein sequences. Genome-wide experimental identification of protein sorting signals is extremely time-consuming and costly. Effective computational algorithms for de novo discovery of protein sorting signals is needed to improve the understanding of protein sorting mechanisms. We formulated the protein sorting motif discovery problem as a classification problem and proposed a Bayesian classifier based algorithm (BayesMotif) for de novo identification of a common type of protein sorting motifs in which a highly conserved anchor is present along with a less conserved motif regions. A false positive removal procedure is developed to iteratively remove sequences that are unlikely to contain true motifs so that the algorithm can identify motifs from impure input sequences. Experiments on both implanted motif datasets and real-world datasets showed that the enhanced BayesMotif algorithm can identify anchored sorting motifs from pure or impure protein sequence dataset. It also shows that the false positive removal procedure can help to identify true motifs even when there is only 20% of the input sequences containing true motif instances. We proposed BayesMotif, a novel Bayesian classification based algorithm for de novo discovery of a special category of anchored protein sorting motifs from impure datasets. Compared to conventional motif discovery algorithms such as MEME, our algorithm can find less-conserved motifs with short highly conserved anchors. Our algorithm also has the advantage of easy incorporation of additional meta-sequence features such as hydrophobicity or charge of the motifs which may help to overcome the limitations of

  13. Modified Phenomena Identification and Ranking Table (PIRT) for Uncertainty Analysis

    International Nuclear Information System (INIS)

    Gol-Mohamad, Mohammad P.; Modarres, Mohammad; Mosleh, Ali

    2006-01-01

    This paper describes a methodology of characterizing important phenomena, which is also part of a broader research by the authors called 'Modified PIRT'. The methodology provides robust process of phenomena identification and ranking process for more precise quantification of uncertainty. It is a two-step process of identifying and ranking methodology based on thermal-hydraulics (TH) importance as well as uncertainty importance. Analytical Hierarchical Process (AHP) has been used for as a formal approach for TH identification and ranking. Formal uncertainty importance technique is used to estimate the degree of credibility of the TH model(s) used to represent the important phenomena. This part uses subjective justification by evaluating available information and data from experiments, and code predictions. The proposed methodology was demonstrated by developing a PIRT for large break loss of coolant accident LBLOCA for the LOFT integral facility with highest core power (test LB-1). (authors)

  14. Identification of coupling DNA motif pairs on long-range chromatin interactions in human K562 cells

    KAUST Repository

    Wong, Ka-Chun; Li, Yue; Peng, Chengbin

    2015-01-01

    Motivation: The protein-DNA interactions between transcription factors (TFs) and transcription factor binding sites (TFBSs, also known as DNA motifs) are critical activities in gene transcription. The identification of the DNA motifs is a vital task for downstream analysis. Unfortunately, the long-range coupling information between different DNA motifs is still lacking. To fill the void, as the first-of-its-kind study, we have identified the coupling DNA motif pairs on long-range chromatin interactions in human. Results: The coupling DNA motif pairs exhibit substantially higher DNase accessibility than the background sequences. Half of the DNA motifs involved are matched to the existing motif databases, although nearly all of them are enriched with at least one gene ontology term. Their motif instances are also found statistically enriched on the promoter and enhancer regions. Especially, we introduce a novel measurement called motif pairing multiplicity which is defined as the number of motifs that are paired with a given motif on chromatin interactions. Interestingly, we observe that motif pairing multiplicity is linked to several characteristics such as regulatory region type, motif sequence degeneracy, DNase accessibility and pairing genomic distance. Taken into account together, we believe the coupling DNA motif pairs identified in this study can shed lights on the gene transcription mechanism under long-range chromatin interactions. © The Author 2015. Published by Oxford University Press.

  15. Identification of coupling DNA motif pairs on long-range chromatin interactions in human K562 cells

    KAUST Repository

    Wong, Ka-Chun

    2015-09-27

    Motivation: The protein-DNA interactions between transcription factors (TFs) and transcription factor binding sites (TFBSs, also known as DNA motifs) are critical activities in gene transcription. The identification of the DNA motifs is a vital task for downstream analysis. Unfortunately, the long-range coupling information between different DNA motifs is still lacking. To fill the void, as the first-of-its-kind study, we have identified the coupling DNA motif pairs on long-range chromatin interactions in human. Results: The coupling DNA motif pairs exhibit substantially higher DNase accessibility than the background sequences. Half of the DNA motifs involved are matched to the existing motif databases, although nearly all of them are enriched with at least one gene ontology term. Their motif instances are also found statistically enriched on the promoter and enhancer regions. Especially, we introduce a novel measurement called motif pairing multiplicity which is defined as the number of motifs that are paired with a given motif on chromatin interactions. Interestingly, we observe that motif pairing multiplicity is linked to several characteristics such as regulatory region type, motif sequence degeneracy, DNase accessibility and pairing genomic distance. Taken into account together, we believe the coupling DNA motif pairs identified in this study can shed lights on the gene transcription mechanism under long-range chromatin interactions. © The Author 2015. Published by Oxford University Press.

  16. Phenomena identification and ranking tables (PIRT) for LBLOCA

    International Nuclear Information System (INIS)

    Shaw, R.A.; Dimenna, R.A.; Larson, T.K.; Wilson, G.E.

    1988-01-01

    The US Nuclear Regulatory Commission is sponsoring a program to provide validated reactor safety computer codes with quantified uncertainties. The intent is to quantify the accuracy of the codes for use in best estimate licensing applications. One of the tasks required to complete this program involves the identification and ranking of thermal-hydraulic phenomena that occur during particular accidents. This paper provides detailed tables of phenomena and importance ranks for a PWR LBLOCA. The phenomena were identified and ranked according to perceived impact on peak cladding temperature. Two approaches were used to complete this task. First, a panel of experts identified the physical processes considered to be most important during LBLOCA. A second team of experienced analysts then, in parallel, assembled complete tables of all plausible LBLOCA phenomena, regardless of perceived importance. Each phenomenon was then ranked in importance against every other phenomenon associated with a given component. The results were placed in matrix format and solved for the principal eigenvector. The results as determined by each method are presented in this report

  17. Spectral-based features ranking for gamelan instruments identification using filter techniques

    Directory of Open Access Journals (Sweden)

    Diah P Wulandari

    2013-03-01

    Full Text Available In this paper, we describe an approach of spectral-based features ranking for Javanese gamelaninstruments identification using filter techniques. The model extracted spectral-based features set of thesignal using Short Time Fourier Transform (STFT. The rank of the features was determined using the fivealgorithms; namely ReliefF, Chi-Squared, Information Gain, Gain Ratio, and Symmetric Uncertainty. Then,we tested the ranked features by cross validation using Support Vector Machine (SVM. The experimentshowed that Gain Ratio algorithm gave the best result, it yielded accuracy of 98.93%.

  18. MotifNet: a web-server for network motif analysis.

    Science.gov (United States)

    Smoly, Ilan Y; Lerman, Eugene; Ziv-Ukelson, Michal; Yeger-Lotem, Esti

    2017-06-15

    Network motifs are small topological patterns that recur in a network significantly more often than expected by chance. Their identification emerged as a powerful approach for uncovering the design principles underlying complex networks. However, available tools for network motif analysis typically require download and execution of computationally intensive software on a local computer. We present MotifNet, the first open-access web-server for network motif analysis. MotifNet allows researchers to analyze integrated networks, where nodes and edges may be labeled, and to search for motifs of up to eight nodes. The output motifs are presented graphically and the user can interactively filter them by their significance, number of instances, node and edge labels, and node identities, and view their instances. MotifNet also allows the user to distinguish between motifs that are centered on specific nodes and motifs that recur in distinct parts of the network. MotifNet is freely available at http://netbio.bgu.ac.il/motifnet . The website was implemented using ReactJs and supports all major browsers. The server interface was implemented in Python with data stored on a MySQL database. estiyl@bgu.ac.il or michaluz@cs.bgu.ac.il. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  19. An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.

    Science.gov (United States)

    Liu, Bingqiang; Zhang, Hanyuan; Zhou, Chuan; Li, Guojun; Fennell, Anne; Wang, Guanghui; Kang, Yu; Liu, Qi; Ma, Qin

    2016-08-09

    Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction. Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP(3)). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP(3) consistently outperformed other popular motif finding tools. We have integrated MP(3) into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes. The performance evaluation indicated that MP(3) is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance

  20. A speedup technique for (l, d-motif finding algorithms

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    Dinh Hieu

    2011-03-01

    Full Text Available Abstract Background The discovery of patterns in DNA, RNA, and protein sequences has led to the solution of many vital biological problems. For instance, the identification of patterns in nucleic acid sequences has resulted in the determination of open reading frames, identification of promoter elements of genes, identification of intron/exon splicing sites, identification of SH RNAs, location of RNA degradation signals, identification of alternative splicing sites, etc. In protein sequences, patterns have proven to be extremely helpful in domain identification, location of protease cleavage sites, identification of signal peptides, protein interactions, determination of protein degradation elements, identification of protein trafficking elements, etc. Motifs are important patterns that are helpful in finding transcriptional regulatory elements, transcription factor binding sites, functional genomics, drug design, etc. As a result, numerous papers have been written to solve the motif search problem. Results Three versions of the motif search problem have been proposed in the literature: Simple Motif Search (SMS, (l, d-motif search (or Planted Motif Search (PMS, and Edit-distance-based Motif Search (EMS. In this paper we focus on PMS. Two kinds of algorithms can be found in the literature for solving the PMS problem: exact and approximate. An exact algorithm identifies the motifs always and an approximate algorithm may fail to identify some or all of the motifs. The exact version of PMS problem has been shown to be NP-hard. Exact algorithms proposed in the literature for PMS take time that is exponential in some of the underlying parameters. In this paper we propose a generic technique that can be used to speedup PMS algorithms. Conclusions We present a speedup technique that can be used on any PMS algorithm. We have tested our speedup technique on a number of algorithms. These experimental results show that our speedup technique is indeed very

  1. Motif-role-fingerprints: the building-blocks of motifs, clustering-coefficients and transitivities in directed networks.

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    Mark D McDonnell

    Full Text Available Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are 'structural' (induced subgraphs and 'functional' (partial subgraphs. Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File.

  2. Accelerating parameter identification of proton exchange membrane fuel cell model with ranking-based differential evolution

    International Nuclear Information System (INIS)

    Gong, Wenyin; Cai, Zhihua

    2013-01-01

    Parameter identification of PEM (proton exchange membrane) fuel cell model is a very active area of research. Generally, it can be treated as a numerical optimization problem with complex nonlinear and multi-variable features. DE (differential evolution), which has been successfully used in various fields, is a simple yet efficient evolutionary algorithm for global numerical optimization. In this paper, with the objective of accelerating the process of parameter identification of PEM fuel cell models and reducing the necessary computational efforts, we firstly present a generic and simple ranking-based mutation operator for the DE algorithm. Then, the ranking-based mutation operator is incorporated into five highly-competitive DE variants to solve the PEM fuel cell model parameter identification problems. The main contributions of this work are the proposed ranking-based DE variants and their application to the parameter identification problems of PEM fuel cell models. Experiments have been conducted by using both the simulated voltage–current data and the data obtained from the literature to validate the performance of our approach. The results indicate that the ranking-based DE methods provide better results with respect to the solution quality, the convergence rate, and the success rate compared with their corresponding original DE methods. In addition, the voltage–current characteristics obtained by our approach are in good agreement with the original voltage–current curves in all cases. - Highlights: • A simple and generic ranking-based mutation operator is presented in this paper. • Several DE (differential evolution) variants are used to solve the parameter identification of PEMFC (proton exchange membrane fuel cells) model. • Results show that our method accelerates the process of parameter identification. • The V–I characteristics are in very good agreement with experimental data

  3. Identification of sequence motifs significantly associated with antisense activity

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    Peek Andrew S

    2007-06-01

    Full Text Available Abstract Background Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. Results We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. Conclusion The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic

  4. Peptomics, identification of novel cationic Arabidopsis peptides with conserved sequence motifs

    DEFF Research Database (Denmark)

    Olsen, Addie Nina; Mundy, John; Skriver, Karen

    2002-01-01

    Arabidopsis family of 34 genes. The predicted peptides are characterized by a conserved C-terminal sequence motif and additional primary structure conservation in a core region. The majority of these genes had not previously been annotated. A subset of the predicted peptides show high overall sequence...... similarity to Rapid Alkalinization Factor (RALF), a peptide isolated from tobacco. We therefore refer to this peptide family as RALFL for RALF-Like. RT-PCR analysis confirmed that several of the Arabidopsis genes are expressed and that their expression patterns vary. The identification of a large gene family...

  5. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

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    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  6. Distance-Ranked Fault Identification of Reconfigurable Hardware Bitstreams via Functional Input

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    Naveed Imran

    2014-01-01

    Full Text Available Distance-Ranked Fault Identification (DRFI is a dynamic reconfiguration technique which employs runtime inputs to conduct online functional testing of fielded FPGA logic and interconnect resources without test vectors. At design time, a diverse set of functionally identical bitstream configurations are created which utilize alternate hardware resources in the FPGA fabric. An ordering is imposed on the configuration pool as updated by the PageRank indexing precedence. The configurations which utilize permanently damaged resources and hence manifest discrepant outputs, receive lower rank are thus less preferred for instantiation on the FPGA. Results indicate accurate identification of fault-free configurations in a pool of pregenerated bitstreams with a low number of reconfigurations and input evaluations. For MCNC benchmark circuits, the observed reduction in input evaluations is up to 75% when comparing the DRFI technique to unguided evaluation. The DRFI diagnosis method is seen to isolate all 14 healthy configurations from a pool of 100 pregenerated configurations, and thereby offering a 100% isolation accuracy provided the fault-free configurations exist in the design pool. When a complete recovery is not feasible, graceful degradation may be realized which is demonstrated by the PSNR improvement of images processed in a video encoder case study.

  7. Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification

    Science.gov (United States)

    Faye, Laura L.; Machiela, Mitchell J.; Kraft, Peter; Bull, Shelley B.; Sun, Lei

    2013-01-01

    Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-use of GWAS data for fine-mapping exploits previous findings to ensure genome-wide significance in GWAS-associated regions. However, using GWAS findings to inform fine-mapping analysis can bias evidence away from the causal SNP toward the tag SNP and SNPs in high LD with the tag. Together these factors can reduce power to localize the causal SNP by more than half. Other strategies commonly employed to increase power to detect association, namely increasing sample size and using higher density genotyping arrays, can, in certain common scenarios, actually exacerbate these effects and further decrease power to localize causal variants. We develop a re-ranking procedure that accounts for these adverse effects and substantially improves the accuracy of causal SNP identification, often doubling the probability that the causal SNP is top-ranked. Application to the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis identified a new top SNP at 2 of 3 associated loci and several additional possible causal SNPs at these loci that may have otherwise been overlooked. This method is simple to implement using R scripts provided on the author's website. PMID:23950724

  8. Identification of significant features by the Global Mean Rank test.

    Science.gov (United States)

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2014-01-01

    With the introduction of omics-technologies such as transcriptomics and proteomics, numerous methods for the reliable identification of significantly regulated features (genes, proteins, etc.) have been developed. Experimental practice requires these tests to successfully deal with conditions such as small numbers of replicates, missing values, non-normally distributed expression levels, and non-identical distributions of features. With the MeanRank test we aimed at developing a test that performs robustly under these conditions, while favorably scaling with the number of replicates. The test proposed here is a global one-sample location test, which is based on the mean ranks across replicates, and internally estimates and controls the false discovery rate. Furthermore, missing data is accounted for without the need of imputation. In extensive simulations comparing MeanRank to other frequently used methods, we found that it performs well with small and large numbers of replicates, feature dependent variance between replicates, and variable regulation across features on simulation data and a recent two-color microarray spike-in dataset. The tests were then used to identify significant changes in the phosphoproteomes of cancer cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two independently published mass spectrometry-based studies. MeanRank outperformed the other global rank-based methods applied in this study. Compared to the popular Significance Analysis of Microarrays and Linear Models for Microarray methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits more consistent behavior regarding the degree of regulation and is robust against the choice of preprocessing methods. MeanRank does not require any imputation of missing values, is easy to understand, and yields results that are easy to interpret. The software implementing the algorithm is freely available for academic and commercial use.

  9. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Science.gov (United States)

    Fauteux, François; Strömvik, Martina V

    2009-01-01

    Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP) gene promoters from three plant families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae (grasses) using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.) respectively. We have identified three conserved motifs (two RY-like and one ACGT-like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination of conserved motifs

  10. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Directory of Open Access Journals (Sweden)

    Fauteux François

    2009-10-01

    Full Text Available Abstract Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP gene promoters from three plant families, namely Brassicaceae (mustards, Fabaceae (legumes and Poaceae (grasses using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L. Heynh., soybean (Glycine max (L. Merr. and rice (Oryza sativa L. respectively. We have identified three conserved motifs (two RY-like and one ACGT-like in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination

  11. Identification of early zygotic genes in the yellow fever mosquito Aedes aegypti and discovery of a motif involved in early zygotic genome activation.

    Science.gov (United States)

    Biedler, James K; Hu, Wanqi; Tae, Hongseok; Tu, Zhijian

    2012-01-01

    During early embryogenesis the zygotic genome is transcriptionally silent and all mRNAs present are of maternal origin. The maternal-zygotic transition marks the time over which embryogenesis changes its dependence from maternal RNAs to zygotically transcribed RNAs. Here we present the first systematic investigation of early zygotic genes (EZGs) in a mosquito species and focus on genes involved in the onset of transcription during 2-4 hr. We used transcriptome sequencing to identify the "pure" (without maternal expression) EZGs by analyzing transcripts from four embryonic time ranges of 0-2, 2-4, 4-8, and 8-12 hr, which includes the time of cellular blastoderm formation and up to the start of gastrulation. Blast of 16,789 annotated transcripts vs. the transcriptome reads revealed evidence for 63 (P<0.001) and 143 (P<0.05) nonmaternally derived transcripts having a significant increase in expression at 2-4 hr. One third of the 63 EZG transcripts do not have predicted introns compared to 10% of all Ae. aegypti genes. We have confirmed by RT-PCR that zygotic transcription starts as early as 2-3 hours. A degenerate motif VBRGGTA was found to be overrepresented in the upstream sequences of the identified EZGs using a motif identification software called SCOPE. We find evidence for homology between this motif and the TAGteam motif found in Drosophila that has been implicated in EZG activation. A 38 bp sequence in the proximal upstream sequence of a kinesin light chain EZG (KLC2.1) contains two copies of the mosquito motif. This sequence was shown to support EZG transcription by luciferase reporter assays performed on injected early embryos, and confers early zygotic activity to a heterologous promoter from a divergent mosquito species. The results of these studies are consistent with the model of early zygotic genome activation via transcriptional activators, similar to what has been found recently in Drosophila.

  12. Identification of early zygotic genes in the yellow fever mosquito Aedes aegypti and discovery of a motif involved in early zygotic genome activation.

    Directory of Open Access Journals (Sweden)

    James K Biedler

    Full Text Available During early embryogenesis the zygotic genome is transcriptionally silent and all mRNAs present are of maternal origin. The maternal-zygotic transition marks the time over which embryogenesis changes its dependence from maternal RNAs to zygotically transcribed RNAs. Here we present the first systematic investigation of early zygotic genes (EZGs in a mosquito species and focus on genes involved in the onset of transcription during 2-4 hr. We used transcriptome sequencing to identify the "pure" (without maternal expression EZGs by analyzing transcripts from four embryonic time ranges of 0-2, 2-4, 4-8, and 8-12 hr, which includes the time of cellular blastoderm formation and up to the start of gastrulation. Blast of 16,789 annotated transcripts vs. the transcriptome reads revealed evidence for 63 (P<0.001 and 143 (P<0.05 nonmaternally derived transcripts having a significant increase in expression at 2-4 hr. One third of the 63 EZG transcripts do not have predicted introns compared to 10% of all Ae. aegypti genes. We have confirmed by RT-PCR that zygotic transcription starts as early as 2-3 hours. A degenerate motif VBRGGTA was found to be overrepresented in the upstream sequences of the identified EZGs using a motif identification software called SCOPE. We find evidence for homology between this motif and the TAGteam motif found in Drosophila that has been implicated in EZG activation. A 38 bp sequence in the proximal upstream sequence of a kinesin light chain EZG (KLC2.1 contains two copies of the mosquito motif. This sequence was shown to support EZG transcription by luciferase reporter assays performed on injected early embryos, and confers early zygotic activity to a heterologous promoter from a divergent mosquito species. The results of these studies are consistent with the model of early zygotic genome activation via transcriptional activators, similar to what has been found recently in Drosophila.

  13. Evidence for the additions of clustered interacting nodes during the evolution of protein interaction networks from network motifs

    Directory of Open Access Journals (Sweden)

    Guo Hao

    2011-05-01

    Full Text Available Abstract Background High-throughput screens have revealed large-scale protein interaction networks defining most cellular functions. How the proteins were added to the protein interaction network during its growth is a basic and important issue. Network motifs represent the simplest building blocks of cellular machines and are of biological significance. Results Here we study the evolution of protein interaction networks from the perspective of network motifs. We find that in current protein interaction networks, proteins of the same age class tend to form motifs and such co-origins of motif constituents are affected by their topologies and biological functions. Further, we find that the proteins within motifs whose constituents are of the same age class tend to be densely interconnected, co-evolve and share the same biological functions, and these motifs tend to be within protein complexes. Conclusions Our findings provide novel evidence for the hypothesis of the additions of clustered interacting nodes and point out network motifs, especially the motifs with the dense topology and specific function may play important roles during this process. Our results suggest functional constraints may be the underlying driving force for such additions of clustered interacting nodes.

  14. Research on the Fusion of Dependent Evidence Based on Rank Correlation Coefficient

    Directory of Open Access Journals (Sweden)

    Fengjian Shi

    2017-10-01

    Full Text Available In order to meet the higher accuracy and system reliability requirements, the information fusion for multi-sensor systems is an increasing concern. Dempster–Shafer evidence theory (D–S theory has been investigated for many applications in multi-sensor information fusion due to its flexibility in uncertainty modeling. However, classical evidence theory assumes that the evidence is independent of each other, which is often unrealistic. Ignoring the relationship between the evidence may lead to unreasonable fusion results, and even lead to wrong decisions. This assumption severely prevents D–S evidence theory from practical application and further development. In this paper, an innovative evidence fusion model to deal with dependent evidence based on rank correlation coefficient is proposed. The model first uses rank correlation coefficient to measure the dependence degree between different evidence. Then, total discount coefficient is obtained based on the dependence degree, which also considers the impact of the reliability of evidence. Finally, the discount evidence fusion model is presented. An example is illustrated to show the use and effectiveness of the proposed method.

  15. Research on the Fusion of Dependent Evidence Based on Rank Correlation Coefficient.

    Science.gov (United States)

    Shi, Fengjian; Su, Xiaoyan; Qian, Hong; Yang, Ning; Han, Wenhua

    2017-10-16

    In order to meet the higher accuracy and system reliability requirements, the information fusion for multi-sensor systems is an increasing concern. Dempster-Shafer evidence theory (D-S theory) has been investigated for many applications in multi-sensor information fusion due to its flexibility in uncertainty modeling. However, classical evidence theory assumes that the evidence is independent of each other, which is often unrealistic. Ignoring the relationship between the evidence may lead to unreasonable fusion results, and even lead to wrong decisions. This assumption severely prevents D-S evidence theory from practical application and further development. In this paper, an innovative evidence fusion model to deal with dependent evidence based on rank correlation coefficient is proposed. The model first uses rank correlation coefficient to measure the dependence degree between different evidence. Then, total discount coefficient is obtained based on the dependence degree, which also considers the impact of the reliability of evidence. Finally, the discount evidence fusion model is presented. An example is illustrated to show the use and effectiveness of the proposed method.

  16. Triadic motifs in the dependence networks of virtual societies

    Science.gov (United States)

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  17. Triadic motifs in the dependence networks of virtual societies.

    Science.gov (United States)

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-10

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  18. A methodology for ranking and hazard identification of xenobiotic organic compounds in urban stormwater

    DEFF Research Database (Denmark)

    Baun, Anders; Eriksson, Eva; Ledin, Anna

    2006-01-01

    The paper presents a novel methodology (RICH, Ranking and Identification of Chemical Hazards) for ranking and identification of xenobiotic organic compounds of environmental concern in stormwater discharged to surface water. The RICHmethod is illustrated as a funnel fitted with different filters...... in hazard/risk assessments, a justified list of stormwater priority pollutants which must be included in hazard/risk assessments, and a list of compounds which may be present in discharged stormwater, but cannot be evaluated due to lack of data. The procedure was applied to 233 xenobiotic organic chemicals...... with xenobiotic organic compounds (XOCs) found in urban stormwater, but it may be transferred to other environmental compartments and problems. Thus, the RICH procedure can be used as a stand-alone tool for selection of potential priority pollutants or it can be integrated in larger priority setting frameworks....

  19. RMOD: a tool for regulatory motif detection in signaling network.

    Directory of Open Access Journals (Sweden)

    Jinki Kim

    Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

  20. Reduced-Rank Shift-Invariant Technique and Its Application for Synchronization and Channel Identification in UWB Systems

    Directory of Open Access Journals (Sweden)

    Kennedy RodneyA

    2008-01-01

    Full Text Available Abstract We investigate reduced-rank shift-invariant technique and its application for synchronization and channel identification in UWB systems. Shift-invariant techniques, such as ESPRIT and the matrix pencil method, have high resolution ability, but the associated high complexity makes them less attractive in real-time implementations. Aiming at reducing the complexity, we developed novel reduced-rank identification of principal components (RIPC algorithms. These RIPC algorithms can automatically track the principal components and reduce the computational complexity significantly by transforming the generalized eigen-problem in an original high-dimensional space to a lower-dimensional space depending on the number of desired principal signals. We then investigate the application of the proposed RIPC algorithms for joint synchronization and channel estimation in UWB systems, where general correlator-based algorithms confront many limitations. Technical details, including sampling and the capture of synchronization delay, are provided. Experimental results show that the performance of the RIPC algorithms is only slightly inferior to the general full-rank algorithms.

  1. AP600 passive containment cooling system phenomena identification and ranking table

    International Nuclear Information System (INIS)

    Spencer, D.R.; Woodcock, Joel

    1999-01-01

    This paper presents the Phenomena Identification and Ranking Table (PIRT) used in the containment Design Basis Analysis (DBA) for the AP600 nuclear power plant. The PIRT is a tool generally applied to best estimate thermal hydraulic analyses. In the conservative analytical modeling approach used for the AP600 DBA containment pressure response, the PIRT was a tool used to show completeness and relevance of the test database in accordance with the Code of Federal Regulations for advanced plant design. Additionally, the ranking of phenomena by relative importance in a PIRT allows appropriate focusing of resources during model development and licensing review. The focus of the paper is on the organization and structure of the PIRT to show level of detail and format accepted for the AP600, for potential application to other containment designs or accident scenarios. Conclusions of general interest are discussed regarding table organization and structure, the process for developing relative ranking and incorporating expert opinion, and the definition and usage of the relative ranking in support of the conservative evaluation model. The AP600 containment evaluation model approach, as influenced by the relative rankings, is briefly described to put into context this unique application of the PIRT to a conservative methodology. The bases for relative ranking of each phenomenon, which included expert opinion, and quantitative results of scaling and testing, was submitted to the NRC as part of AP600-specific evaluations. Since a PIRT supports the sufficiency of both a testing program and analytical modeling, the process followed to generate and confirm the PIRT, an important part of the licensing acceptance, was a focus of extensive NRC review. General descriptions of key phenomena are provided to aid in understanding the containment PIRT for more general applications for containment evaluations of other PWR designs or for other scenarios. (author)

  2. The main determinants of international student identification with a UK middle ranking business school corporate brand: an international marketing perspective

    OpenAIRE

    Mahmoud, Rudaina

    2014-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. The aim of this study is to make a theoretical contribution vis-à-vis the main determinants of international student identification with a middle ranking business school corporate brand. The findings of this study are of foundational significance in theory building terms. A substantive theory of international postgraduate student identification in UK middle ranking business school corporate b...

  3. Communities in Large Networks: Identification and Ranking

    DEFF Research Database (Denmark)

    Olsen, Martin

    2008-01-01

    We study the problem of identifying and ranking the members of a community in a very large network with link analysis only, given a set of representatives of the community. We define the concept of a community justified by a formal analysis of a simple model of the evolution of a directed graph. ...... and its immediate surroundings. The members are ranked with a “local” variant of the PageRank algorithm. Results are reported from successful experiments on identifying and ranking Danish Computer Science sites and Danish Chess pages using only a few representatives....

  4. Application of Parallel Hierarchical Matrices and Low-Rank Tensors in Spatial Statistics and Parameter Identification

    KAUST Repository

    Litvinenko, Alexander

    2018-03-12

    Part 1: Parallel H-matrices in spatial statistics 1. Motivation: improve statistical model 2. Tools: Hierarchical matrices 3. Matern covariance function and joint Gaussian likelihood 4. Identification of unknown parameters via maximizing Gaussian log-likelihood 5. Implementation with HLIBPro. Part 2: Low-rank Tucker tensor methods in spatial statistics

  5. Identification and ranking of environmental threats with ecosystem vulnerability distributions.

    Science.gov (United States)

    Zijp, Michiel C; Huijbregts, Mark A J; Schipper, Aafke M; Mulder, Christian; Posthuma, Leo

    2017-08-24

    Responses of ecosystems to human-induced stress vary in space and time, because both stressors and ecosystem vulnerabilities vary in space and time. Presently, ecosystem impact assessments mainly take into account variation in stressors, without considering variation in ecosystem vulnerability. We developed a method to address ecosystem vulnerability variation by quantifying ecosystem vulnerability distributions (EVDs) based on monitoring data of local species compositions and environmental conditions. The method incorporates spatial variation of both abiotic and biotic variables to quantify variation in responses among species and ecosystems. We show that EVDs can be derived based on a selection of locations, existing monitoring data and a selected impact boundary, and can be used in stressor identification and ranking for a region. A case study on Ohio's freshwater ecosystems, with freshwater fish as target species group, showed that physical habitat impairment and nutrient loads ranked highest as current stressors, with species losses higher than 5% for at least 6% of the locations. EVDs complement existing approaches of stressor assessment and management, which typically account only for variability in stressors, by accounting for variation in the vulnerability of the responding ecosystems.

  6. Assessing local structure motifs using order parameters for motif recognition, interstitial identification, and diffusion path characterization

    Science.gov (United States)

    Zimmermann, Nils E. R.; Horton, Matthew K.; Jain, Anubhav; Haranczyk, Maciej

    2017-11-01

    Structure-property relationships form the basis of many design rules in materials science, including synthesizability and long-term stability of catalysts, control of electrical and optoelectronic behavior in semiconductors as well as the capacity of and transport properties in cathode materials for rechargeable batteries. The immediate atomic environments (i.e., the first coordination shells) of a few atomic sites are often a key factor in achieving a desired property. Some of the most frequently encountered coordination patterns are tetrahedra, octahedra, body and face-centered cubic as well as hexagonal closed packed-like environments. Here, we showcase the usefulness of local order parameters to identify these basic structural motifs in inorganic solid materials by developing classification criteria. We introduce a systematic testing framework, the Einstein crystal test rig, that probes the response of order parameters to distortions in perfect motifs to validate our approach. Subsequently, we highlight three important application cases. First, we map basic crystal structure information of a large materials database in an intuitive manner by screening the Materials Project (MP) database (61,422 compounds) for element-specific motif distributions. Second, we use the structure-motif recognition capabilities to automatically find interstitials in metals, semiconductor, and insulator materials. Our Interstitialcy Finding Tool (InFiT) facilitates high-throughput screenings of defect properties. Third, the order parameters are reliable and compact quantitative structure descriptors for characterizing diffusion hops of intercalants as our example of magnesium in MnO2-spinel indicates. Finally, the tools developed in our work are readily and freely available as software implementations in the pymatgen library, and we expect them to be further applied to machine-learning approaches for emerging applications in materials science.

  7. DNA motif elucidation using belief propagation.

    Science.gov (United States)

    Wong, Ka-Chun; Chan, Tak-Ming; Peng, Chengbin; Li, Yue; Zhang, Zhaolei

    2013-09-01

    Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k=8∼10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors' websites: e.g. http://www.cs.toronto.edu/∼wkc/kmerHMM.

  8. DNA motif elucidation using belief propagation

    KAUST Repository

    Wong, Ka-Chun; Chan, Tak-Ming; Peng, Chengbin; Li, Yue; Zhang, Zhaolei

    2013-01-01

    Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k = 8 ?10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors' websites: e.g. http://www.cs.toronto.edu/?wkc/kmerHMM. 2013 The Author(s).

  9. DNA motif elucidation using belief propagation

    KAUST Repository

    Wong, Ka-Chun

    2013-06-29

    Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k = 8 ?10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors\\' websites: e.g. http://www.cs.toronto.edu/?wkc/kmerHMM. 2013 The Author(s).

  10. Constrained dictionary learning and probabilistic hypergraph ranking for person re-identification

    Science.gov (United States)

    He, You; Wu, Song; Pu, Nan; Qian, Li; Xiao, Guoqiang

    2018-04-01

    Person re-identification is a fundamental and inevitable task in public security. In this paper, we propose a novel framework to improve the performance of this task. First, two different types of descriptors are extracted to represent a pedestrian: (1) appearance-based superpixel features, which are constituted mainly by conventional color features and extracted from the supepixel rather than a whole picture and (2) due to the limitation of discrimination of appearance features, the deep features extracted by feature fusion Network are also used. Second, a view invariant subspace is learned by dictionary learning constrained by the minimum negative sample (termed as DL-cMN) to reduce the noise in appearance-based superpixel feature domain. Then, we use deep features and sparse codes transformed by appearancebased features to establish the hyperedges respectively by k-nearest neighbor, rather than jointing different features simply. Finally, a final ranking is performed by probabilistic hypergraph ranking algorithm. Extensive experiments on three challenging datasets (VIPeR, PRID450S and CUHK01) demonstrate the advantages and effectiveness of our proposed algorithm.

  11. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    International Nuclear Information System (INIS)

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-01-01

    Highlights: ► We found the putative nuclear export signal motif within human NANOG homeodomain. ► Leucine-rich residues are important for human NANOG homeodomain nuclear export. ► CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ( 125 MQELSNILNL 134 ) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-ΔNLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  12. Assessing Local Structure Motifs Using Order Parameters for Motif Recognition, Interstitial Identification, and Diffusion Path Characterization

    Directory of Open Access Journals (Sweden)

    Nils E. R. Zimmermann

    2017-11-01

    Full Text Available Structure–property relationships form the basis of many design rules in materials science, including synthesizability and long-term stability of catalysts, control of electrical and optoelectronic behavior in semiconductors, as well as the capacity of and transport properties in cathode materials for rechargeable batteries. The immediate atomic environments (i.e., the first coordination shells of a few atomic sites are often a key factor in achieving a desired property. Some of the most frequently encountered coordination patterns are tetrahedra, octahedra, body and face-centered cubic as well as hexagonal close packed-like environments. Here, we showcase the usefulness of local order parameters to identify these basic structural motifs in inorganic solid materials by developing classification criteria. We introduce a systematic testing framework, the Einstein crystal test rig, that probes the response of order parameters to distortions in perfect motifs to validate our approach. Subsequently, we highlight three important application cases. First, we map basic crystal structure information of a large materials database in an intuitive manner by screening the Materials Project (MP database (61,422 compounds for element-specific motif distributions. Second, we use the structure-motif recognition capabilities to automatically find interstitials in metals, semiconductor, and insulator materials. Our Interstitialcy Finding Tool (InFiT facilitates high-throughput screenings of defect properties. Third, the order parameters are reliable and compact quantitative structure descriptors for characterizing diffusion hops of intercalants as our example of magnesium in MnO2-spinel indicates. Finally, the tools developed in our work are readily and freely available as software implementations in the pymatgen library, and we expect them to be further applied to machine-learning approaches for emerging applications in materials science.

  13. Communities in Large Networks: Identification and Ranking

    DEFF Research Database (Denmark)

    Olsen, Martin

    2008-01-01

    show that the problem of deciding whether a non trivial community exists is NP complete. Nevertheless, experiments show that a very simple greedy approach can identify members of a community in the Danish part of the web graph with time complexity only dependent on the size of the found community...... and its immediate surroundings. The members are ranked with a “local” variant of the PageRank algorithm. Results are reported from successful experiments on identifying and ranking Danish Computer Science sites and Danish Chess pages using only a few representatives....

  14. Development of a phenomena identification and ranking table using fuzzy set theory

    International Nuclear Information System (INIS)

    Kljenak, I.; Jordan Cizelj, R.; Prosek, A.

    2001-01-01

    The use of fuzzy set theory in the development of Phenomena Identification and Ranking Table for a nuclear power plant transient is presented. Fuzzy set theory was used to aggregate the opinions from different experts concerning the importance of individual basic phenomena with respect to safety criteria. The use of fuzzy set theory is particularly adequate, as experts' opinions are inherently imprecise and uncertain. The method is presented on the specific case of a small-break loss-of-coolant accident in a two-loop pressurized water reactor. (author)

  15. CompariMotif: quick and easy comparisons of sequence motifs.

    Science.gov (United States)

    Edwards, Richard J; Davey, Norman E; Shields, Denis C

    2008-05-15

    CompariMotif is a novel tool for making motif-motif comparisons, identifying and describing similarities between regular expression motifs. CompariMotif can identify a number of different relationships between motifs, including exact matches, variants of degenerate motifs and complex overlapping motifs. Motif relationships are scored using shared information content, allowing the best matches to be easily identified in large comparisons. Many input and search options are available, enabling a list of motifs to be compared to itself (to identify recurring motifs) or to datasets of known motifs. CompariMotif can be run online at http://bioware.ucd.ie/ and is freely available for academic use as a set of open source Python modules under a GNU General Public License from http://bioinformatics.ucd.ie/shields/software/comparimotif/

  16. Identification of a Baeyer-Villiger monooxygenase sequence motif

    NARCIS (Netherlands)

    Fraaije, MW; Kamerbeek, NM; van Berkel, WJH; Janssen, DB; Kamerbeek, Nanne M.; Berkel, Willem J.H. van

    2002-01-01

    Baeyer-Villiger monooxygenases (BVMOs) form a distinct class of flavoproteins that catalyze the insertion of an oxygen atom in a C-C bond using dioxygen and NAD(P)H. Using newly characterized BVMO sequences, we have uncovered a BVMO-identifying sequence motif: FXGXXXRXXXW(P/D). Studies with

  17. Identification of group specific motifs in Beta-lactamase family of proteins

    Directory of Open Access Journals (Sweden)

    Saxena Akansha

    2009-12-01

    Full Text Available Abstract Background Beta-lactamases are one of the most serious threats to public health. In order to combat this threat we need to study the molecular and functional diversity of these enzymes and identify signatures specific to these enzymes. These signatures will enable us to develop inhibitors and diagnostic probes specific to lactamases. The existing classification of beta-lactamases was developed nearly 30 years ago when few lactamases were available. DLact database contain more than 2000 beta-lactamase, which can be used to study the molecular diversity and to identify signatures specific to this family. Methods A set of 2020 beta-lactamase proteins available in the DLact database http://59.160.102.202/DLact were classified using graph-based clustering of Best Bi-Directional Hits. Non-redundant (> 90 percent identical protein sequences from each group were aligned using T-Coffee and annotated using information available in literature. Motifs specific to each group were predicted using PRATT program. Results The graph-based classification of beta-lactamase proteins resulted in the formation of six groups (Four major groups containing 191, 726, 774 and 73 proteins while two minor groups containing 50 and 8 proteins. Based on the information available in literature, we found that each of the four major groups correspond to the four classes proposed by Ambler. The two minor groups were novel and do not contain molecular signatures of beta-lactamase proteins reported in literature. The group-specific motifs showed high sensitivity (> 70% and very high specificity (> 90%. The motifs from three groups (corresponding to class A, C and D had a high level of conservation at DNA as well as protein level whereas the motifs from the fourth group (corresponding to class B showed conservation at only protein level. Conclusion The graph-based classification of beta-lactamase proteins corresponds with the classification proposed by Ambler, thus there is

  18. Design of character-based DNA barcode motif for species identification: A computational approach and its validation in fishes.

    Science.gov (United States)

    Chakraborty, Mohua; Dhar, Bishal; Ghosh, Sankar Kumar

    2017-11-01

    The DNA barcodes are generally interpreted using distance-based and character-based methods. The former uses clustering of comparable groups, based on the relative genetic distance, while the latter is based on the presence or absence of discrete nucleotide substitutions. The distance-based approach has a limitation in defining a universal species boundary across the taxa as the rate of mtDNA evolution is not constant throughout the taxa. However, character-based approach more accurately defines this using a unique set of nucleotide characters. The character-based analysis of full-length barcode has some inherent limitations, like sequencing of the full-length barcode, use of a sparse-data matrix and lack of a uniform diagnostic position for each group. A short continuous stretch of a fragment can be used to resolve the limitations. Here, we observe that a 154-bp fragment, from the transversion-rich domain of 1367 COI barcode sequences can successfully delimit species in the three most diverse orders of freshwater fishes. This fragment is used to design species-specific barcode motifs for 109 species by the character-based method, which successfully identifies the correct species using a pattern-matching program. The motifs also correctly identify geographically isolated population of the Cypriniformes species. Further, this region is validated as a species-specific mini-barcode for freshwater fishes by successful PCR amplification and sequencing of the motif (154 bp) using the designed primers. We anticipate that use of such motifs will enhance the diagnostic power of DNA barcode, and the mini-barcode approach will greatly benefit the field-based system of rapid species identification. © 2017 John Wiley & Sons Ltd.

  19. Development of phenomena identification and ranking table for APR1400 main steam line break

    International Nuclear Information System (INIS)

    Song, J. H.; Chung, B. D.; Jeong, J. J.

    2003-01-01

    A Phenomena Identification and Ranking Table (PIRT) was developed for the Main Steam Line Break (MSLB) event of an APR-1400 (Advanced Power Reactor-1400). A team of experts from research institutes, industries, and regulatory bodies participated in the development. The selected event was a double-ended steam line break at full power with the reactor coolant pump running. The panel selected the fuel performance as the primary safety criterion for ranking. The plant design data, the results of APR-1400 safety analysis, and the results of additional best estimate analysis by MARS2.1 were utilized. Three phases of pre-trip, rapid cool-down, and safety injection phase were identified. Then, the ranking of a system, components, phenomenon/process based on the relative importance to the primary evaluation criterion were followed for each time phase. Finally, the knowledge-level for each important process in the component was ranked in terms of the existing knowledge. The highly ranked phenomena identified for APR-1400 MSLB are tube wall heat transfer at the steam generator shell, void distribution at the steam generator shell, liquid entrainment in the separators, mixture level in the separators, boron mixing in the upper down comer, boron transport and thermal mixing in the lower plenum, stored energy release in the upper head, and flow to and/from the upper head. The PIRT will be used as a guide in planning cost effective experimental programs and code development efforts, especially for the quantification of the process and/or phenomena, which have a high importance but low knowledge level

  20. Identification of multiple distinct Snf2 subfamilies with conserved structural motifs.

    Science.gov (United States)

    Flaus, Andrew; Martin, David M A; Barton, Geoffrey J; Owen-Hughes, Tom

    2006-01-01

    The Snf2 family of helicase-related proteins includes the catalytic subunits of ATP-dependent chromatin remodelling complexes found in all eukaryotes. These act to regulate the structure and dynamic properties of chromatin and so influence a broad range of nuclear processes. We have exploited progress in genome sequencing to assemble a comprehensive catalogue of over 1300 Snf2 family members. Multiple sequence alignment of the helicase-related regions enables 24 distinct subfamilies to be identified, a considerable expansion over earlier surveys. Where information is known, there is a good correlation between biological or biochemical function and these assignments, suggesting Snf2 family motor domains are tuned for specific tasks. Scanning of complete genomes reveals all eukaryotes contain members of multiple subfamilies, whereas they are less common and not ubiquitous in eubacteria or archaea. The large sample of Snf2 proteins enables additional distinguishing conserved sequence blocks within the helicase-like motor to be identified. The establishment of a phylogeny for Snf2 proteins provides an opportunity to make informed assignments of function, and the identification of conserved motifs provides a framework for understanding the mechanisms by which these proteins function.

  1. Rapid identification of DNA-binding proteins by mass spectrometry

    DEFF Research Database (Denmark)

    Nordhoff, E.; Korgsdam, A.-M.; Jørgensen, H.F.

    1999-01-01

    We report a protocol for the rapid identification of DNA-binding proteins. Immobilized DNA probes harboring a specific sequence motif are incubated with cell or nuclear extract. Proteins are analyzed directly off the solid support by matrix-assisted laser desorption/ionization time-of-flight mass...... was validated by the identification of known prokaryotic and eukaryotic DNA-binding proteins, and its use provided evidence that poly(ADP-ribose) polymerase exhibits DNA sequence-specific binding to DNA....

  2. Next Generation Nuclear Plant Phenomena Identification and Ranking Tables (PIRTs) Volume 5: Graphite PIRTs

    International Nuclear Information System (INIS)

    Burchell, Timothy D.; Bratton, Rob; Marsden, Barry; Srinivasan, Makuteswara; Penfield, Scott; Mitchell, Mark; Windes, Will

    2008-01-01

    Here we report the outcome of the application of the Nuclear Regulatory Commission (NRC) Phenomena Identification and Ranking Table (PIRT) process to the issue of nuclear-grade graphite for the moderator and structural components of a next generation nuclear plant (NGNP), considering both routine (normal operation) and postulated accident conditions for the NGNP. The NGNP is assumed to be a modular high-temperature gas-cooled reactor (HTGR), either a gas-turbine modular helium reactor (GTMHR) version (a prismatic-core modular reactor (PMR)] or a pebble-bed modular reactor (PBMR) version (a pebble bed reactor (PBR)] design, with either a direct- or indirect-cycle gas turbine (Brayton cycle) system for electric power production, and an indirect-cycle component for hydrogen production. NGNP design options with a high-pressure steam generator (Rankine cycle) in the primary loop are not considered in this PIRT. This graphite PIRT was conducted in parallel with four other NRC PIRT activities, taking advantage of the relationships and overlaps in subject matter. The graphite PIRT panel identified numerous phenomena, five of which were ranked high importance-low knowledge. A further nine were ranked with high importance and medium knowledge rank. Two phenomena were ranked with medium importance and low knowledge, and a further 14 were ranked medium importance and medium knowledge rank. The last 12 phenomena were ranked with low importance and high knowledge rank (or similar combinations suggesting they have low priority). The ranking/scoring rationale for the reported graphite phenomena is discussed. Much has been learned about the behavior of graphite in reactor environments in the 60-plus years since the first graphite rectors went into service. The extensive list of references in the Bibliography is plainly testament to this fact. Our current knowledge base is well developed. Although data are lacking for the specific grades being considered for Generation IV (Gen IV

  3. SA-Mot: a web server for the identification of motifs of interest extracted from protein loops.

    Science.gov (United States)

    Regad, Leslie; Saladin, Adrien; Maupetit, Julien; Geneix, Colette; Camproux, Anne-Claude

    2011-07-01

    The detection of functional motifs is an important step for the determination of protein functions. We present here a new web server SA-Mot (Structural Alphabet Motif) for the extraction and location of structural motifs of interest from protein loops. Contrary to other methods, SA-Mot does not focus only on functional motifs, but it extracts recurrent and conserved structural motifs involved in structural redundancy of loops. SA-Mot uses the structural word notion to extract all structural motifs from uni-dimensional sequences corresponding to loop structures. Then, SA-Mot provides a description of these structural motifs using statistics computed in the loop data set and in SCOP superfamily, sequence and structural parameters. SA-Mot results correspond to an interactive table listing all structural motifs extracted from a target structure and their associated descriptors. Using this information, the users can easily locate loop regions that are important for the protein folding and function. The SA-Mot web server is available at http://sa-mot.mti.univ-paris-diderot.fr.

  4. VaRank: a simple and powerful tool for ranking genetic variants

    Directory of Open Access Journals (Sweden)

    Véronique Geoffroy

    2015-03-01

    Full Text Available Background. Most genetic disorders are caused by single nucleotide variations (SNVs or small insertion/deletions (indels. High throughput sequencing has broadened the catalogue of human variation, including common polymorphisms, rare variations or disease causing mutations. However, identifying one variation among hundreds or thousands of others is still a complex task for biologists, geneticists and clinicians.Results. We have developed VaRank, a command-line tool for the ranking of genetic variants detected by high-throughput sequencing. VaRank scores and prioritizes variants annotated either by Alamut Batch or SnpEff. A barcode allows users to quickly view the presence/absence of variants (with homozygote/heterozygote status in analyzed samples. VaRank supports the commonly used VCF input format for variants analysis thus allowing it to be easily integrated into NGS bioinformatics analysis pipelines. VaRank has been successfully applied to disease-gene identification as well as to molecular diagnostics setup for several hundred patients.Conclusions. VaRank is implemented in Tcl/Tk, a scripting language which is platform-independent but has been tested only on Unix environment. The source code is available under the GNU GPL, and together with sample data and detailed documentation can be downloaded from http://www.lbgi.fr/VaRank/.

  5. Direct AUC optimization of regulatory motifs.

    Science.gov (United States)

    Zhu, Lin; Zhang, Hong-Bo; Huang, De-Shuang

    2017-07-15

    The discovery of transcription factor binding site (TFBS) motifs is essential for untangling the complex mechanism of genetic variation under different developmental and environmental conditions. Among the huge amount of computational approaches for de novo identification of TFBS motifs, discriminative motif learning (DML) methods have been proven to be promising for harnessing the discovery power of accumulated huge amount of high-throughput binding data. However, they have to sacrifice accuracy for speed and could fail to fully utilize the information of the input sequences. We propose a novel algorithm called CDAUC for optimizing DML-learned motifs based on the area under the receiver-operating characteristic curve (AUC) criterion, which has been widely used in the literature to evaluate the significance of extracted motifs. We show that when the considered AUC loss function is optimized in a coordinate-wise manner, the cost function of each resultant sub-problem is a piece-wise constant function, whose optimal value can be found exactly and efficiently. Further, a key step of each iteration of CDAUC can be efficiently solved as a computational geometry problem. Experimental results on real world high-throughput datasets illustrate that CDAUC outperforms competing methods for refining DML motifs, while being one order of magnitude faster. Meanwhile, preliminary results also show that CDAUC may also be useful for improving the interpretability of convolutional kernels generated by the emerging deep learning approaches for predicting TF sequences specificities. CDAUC is available at: https://drive.google.com/drive/folders/0BxOW5MtIZbJjNFpCeHlBVWJHeW8 . dshuang@tongji.edu.cn. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  6. Phenomena identification and ranking tables for Westinghouse AP600 small break loss-of-coolant accident, main steam line break, and steam generator tube rupture scenarios

    International Nuclear Information System (INIS)

    Wilson, G.E.; Fletcher, C.D.; Davis, C.B.

    1997-06-01

    This report revision incorporates new experimental evidence regarding AP600 behavior during small break loss-of-coolant accidents. This report documents the results of Phenomena Identification and Ranking Table (PIRT) efforts for the Westinghouse AP600 reactor. The purpose of this PIRT is to identify important phenomena so that they may be addressed in both the experimental programs and the RELAP5/MOD3 systems analysis computer code. In Revision of this report, the responses of AP600 during small break loss-of-coolant accident, main steam line break, and steam generator tube rupture accident scenarios were evaluated by a committee of thermal-hydraulic experts. Committee membership included Idaho National Engineering and Environmental Laboratory staff and recognized thermal-hydraulic experts from outside of the laboratory. Each of the accident scenarios was subdivided into separate, sequential periods or phases. Within each phase, the plant behavior is controlled by, at most, a few thermal-hydraulic processes. The committee identified the phenomena influencing those processes, and ranked ampersand influences as being of high, medium, low, or insignificant importance. The primary product of this effort is a series of tables, one for each phase of each accident scenario, describing the thermal-hydraulic phenomena judged by the committee to be important, and the relative ranking of that importance. The rationales for the phenomena selected and their rankings are provided. This document issue incorporates an update of the small break loss-of-coolant accident portion of the report. This revision is the result of the release of experimental evidence from AP600-related integral test facilities (ROSA/AP600, OSU, and SPES) and thermal-hydraulic expert review. The activities associated with this update were performed during the period from June 1995 through November 1996. 8 refs., 26 figs., 42 tabs

  7. Phenomena identification and ranking tables for Westinghouse AP600 small break loss-of-coolant accident, main steam line break, and steam generator tube rupture scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, G.E.; Fletcher, C.D.; Davis, C.B. [and others

    1997-06-01

    This report revision incorporates new experimental evidence regarding AP600 behavior during small break loss-of-coolant accidents. This report documents the results of Phenomena Identification and Ranking Table (PIRT) efforts for the Westinghouse AP600 reactor. The purpose of this PIRT is to identify important phenomena so that they may be addressed in both the experimental programs and the RELAP5/MOD3 systems analysis computer code. In Revision of this report, the responses of AP600 during small break loss-of-coolant accident, main steam line break, and steam generator tube rupture accident scenarios were evaluated by a committee of thermal-hydraulic experts. Committee membership included Idaho National Engineering and Environmental Laboratory staff and recognized thermal-hydraulic experts from outside of the laboratory. Each of the accident scenarios was subdivided into separate, sequential periods or phases. Within each phase, the plant behavior is controlled by, at most, a few thermal-hydraulic processes. The committee identified the phenomena influencing those processes, and ranked & influences as being of high, medium, low, or insignificant importance. The primary product of this effort is a series of tables, one for each phase of each accident scenario, describing the thermal-hydraulic phenomena judged by the committee to be important, and the relative ranking of that importance. The rationales for the phenomena selected and their rankings are provided. This document issue incorporates an update of the small break loss-of-coolant accident portion of the report. This revision is the result of the release of experimental evidence from AP600-related integral test facilities (ROSA/AP600, OSU, and SPES) and thermal-hydraulic expert review. The activities associated with this update were performed during the period from June 1995 through November 1996. 8 refs., 26 figs., 42 tabs.

  8. Genome-wide identification of VQ motif-containing proteins and their expression profiles under abiotic stresses in maize

    Directory of Open Access Journals (Sweden)

    Weibin eSong

    2016-01-01

    Full Text Available VQ motif-containing proteins play crucial roles in abiotic stress responses in plants. Recent studies have shown that some VQ proteins physically interact with WRKY transcription factors to activate downstream genes. In the present study, we identified and characterized genes encoding VQ motif-containing proteins using the most recent version of the maize genome sequence. In total, 61VQ genes were identified. In a cluster analysis, these genes clustered into nine groups together with their homologous genes in rice and Arabidopsis. Most of the VQ genes (57 out of 61 numbers identified in maize were found to be single-copy genes. Analyses of RNA-seq data obtained using seedlings under long-term drought treatment showed that the expression levels of most ZmVQ genes (41 out of 61 members changed during the drought stress response. Quantitative real-time PCR analyses showed that most of the ZmVQ genes were responsive to NaCl treatment. Also, approximately half of the ZmVQ genes were co-expressed with ZmWRKY genes. The identification of these VQ genes in the maize genome and knowledge of their expression profiles under drought and osmotic stresses will provide a solid foundation for exploring their specific functions in the abiotic stress responses of maize.

  9. A Novel Approach for Identification and Ranking of Road Traffic Accident Hotspots

    Directory of Open Access Journals (Sweden)

    Zahran El-Said M.M.

    2017-01-01

    Full Text Available Road Traffic Accidents (RTA are known to be one of the main causes of fatalities worldwide. One usef ul approach to improve road safety is through the identification of RT A hotspots along a road, so they can be prioritised and treated. This paper introduces an approach based on Geographical Information System (GI S to identify and prioritise RTA hotspots along a road network using historical RTA data. One particular urban road in Brunei with a historically high rate of RT As, Jalan Gadong, was selected as a case study. Five years of historical RTA data were acquired from the relevant authorities and input into a GIS database. GI S analysis was then used to identify the spatial extension of the RT A hotspots. The RT A hotspots were ranked according to three different schemes: frequency, severity and socio-economic impact of RTAs. A composite ranking scheme was also developed to combine these schemes; this enabled the prioritisation and development of intervention and maintenance programmes of the identified RTA hotspots. A visualisation method of the RTA spatial distribution within each identified RTA hotspot was also developed to determine the most risky road stretches within each hotspot, which is important for treatment prioritisation when limited resources are available.

  10. Large-scale discovery of promoter motifs in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Thomas A Down

    2007-01-01

    Full Text Available A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes.

  11. I-motif DNA structures are formed in the nuclei of human cells

    Science.gov (United States)

    Zeraati, Mahdi; Langley, David B.; Schofield, Peter; Moye, Aaron L.; Rouet, Romain; Hughes, William E.; Bryan, Tracy M.; Dinger, Marcel E.; Christ, Daniel

    2018-06-01

    Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.

  12. A model-based approach to operational event groups ranking

    Energy Technology Data Exchange (ETDEWEB)

    Simic, Zdenko [European Commission Joint Research Centre, Petten (Netherlands). Inst. for Energy and Transport; Maqua, Michael [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH (GRS), Koeln (Germany); Wattrelos, Didier [Institut de Radioprotection et de Surete Nucleaire (IRSN), Fontenay-aux-Roses (France)

    2014-04-15

    The operational experience (OE) feedback provides improvements in all industrial activities. Identification of the most important and valuable groups of events within accumulated experience is important in order to focus on a detailed investigation of events. The paper describes the new ranking method and compares it with three others. Methods have been described and applied to OE events utilised by nuclear power plants in France and Germany for twenty years. The results show that different ranking methods only roughly agree on which of the event groups are the most important ones. In the new ranking method the analytical hierarchy process is applied in order to assure consistent and comprehensive weighting determination for ranking indexes. The proposed method allows a transparent and flexible event groups ranking and identification of the most important OE for further more detailed investigation in order to complete the feedback. (orig.)

  13. Phenomena Identification and Ranking Table for K-DEMO

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Kye Min; Kang, Myung Suk; Heo, Gyun Young [Kyung Hee Univ., Yongin (Korea, Republic of); Kim, Hyoung Chan [National Fusion Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    The purpose of this paper is to describe the current status of the Phenomena Identification Ranking Table (PIRT) for the conceptual design of K-DEMO, Korean Fusion DEMO Plant. K-DEMO is to be planned as the first fusion power plant constructed in South Korea. However, several key technologies such as plasma, materials, and cooling still have large uncertainties. There are also no relevant references to facilitate the design process of K-DEMO due to its different size, commercializing purpose, and regulatory framework. It was proposed to define the phenomena of systems, components, and processes in an accident condition. In this paper, PIRT for K-DEMO was described and analysis based on this tool was performed. We have carried out researches related to safety for fusion power plant in collaboration with the academies funded by NFRI during the past 3 years. As part of this research, Integrated Safety Assessment Methodology (ISAM), which was used to develop GEN-IV nuclear systems, was used to determine the technical safety issues and regulatory requirements for K-DEMO. PIRT is one of ISAM tools. It can recognize vulnerabilities of systems and identify the gaps in technical areas requiring additional research. The results through this tool are expected to contribute on detailed design for K-DEMO as guidance for regulatory requirements and safety systems in the future.

  14. Phenomena Identification and Ranking Table for K-DEMO

    International Nuclear Information System (INIS)

    Oh, Kye Min; Kang, Myung Suk; Heo, Gyun Young; Kim, Hyoung Chan

    2013-01-01

    The purpose of this paper is to describe the current status of the Phenomena Identification Ranking Table (PIRT) for the conceptual design of K-DEMO, Korean Fusion DEMO Plant. K-DEMO is to be planned as the first fusion power plant constructed in South Korea. However, several key technologies such as plasma, materials, and cooling still have large uncertainties. There are also no relevant references to facilitate the design process of K-DEMO due to its different size, commercializing purpose, and regulatory framework. It was proposed to define the phenomena of systems, components, and processes in an accident condition. In this paper, PIRT for K-DEMO was described and analysis based on this tool was performed. We have carried out researches related to safety for fusion power plant in collaboration with the academies funded by NFRI during the past 3 years. As part of this research, Integrated Safety Assessment Methodology (ISAM), which was used to develop GEN-IV nuclear systems, was used to determine the technical safety issues and regulatory requirements for K-DEMO. PIRT is one of ISAM tools. It can recognize vulnerabilities of systems and identify the gaps in technical areas requiring additional research. The results through this tool are expected to contribute on detailed design for K-DEMO as guidance for regulatory requirements and safety systems in the future

  15. The limits of de novo DNA motif discovery.

    Directory of Open Access Journals (Sweden)

    David Simcha

    Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of

  16. Assessment of algorithms for inferring positional weight matrix motifs of transcription factor binding sites using protein binding microarray data.

    Directory of Open Access Journals (Sweden)

    Yaron Orenstein

    Full Text Available The new technology of protein binding microarrays (PBMs allows simultaneous measurement of the binding intensities of a transcription factor to tens of thousands of synthetic double-stranded DNA probes, covering all possible 10-mers. A key computational challenge is inferring the binding motif from these data. We present a systematic comparison of four methods developed specifically for reconstructing a binding site motif represented as a positional weight matrix from PBM data. The reconstructed motifs were evaluated in terms of three criteria: concordance with reference motifs from the literature and ability to predict in vivo and in vitro bindings. The evaluation encompassed over 200 transcription factors and some 300 assays. The results show a tradeoff between how the methods perform according to the different criteria, and a dichotomy of method types. Algorithms that construct motifs with low information content predict PBM probe ranking more faithfully, while methods that produce highly informative motifs match reference motifs better. Interestingly, in predicting high-affinity binding, all methods give far poorer results for in vivo assays compared to in vitro assays.

  17. Armadillo motifs involved in vesicular transport.

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    Harald Striegl

    Full Text Available Armadillo (ARM repeat proteins function in various cellular processes including vesicular transport and membrane tethering. They contain an imperfect repeating sequence motif that forms a conserved three-dimensional structure. Recently, structural and functional insight into tethering mediated by the ARM-repeat protein p115 has been provided. Here we describe the p115 ARM-motifs for reasons of clarity and nomenclature and show that both sequence and structure are highly conserved among ARM-repeat proteins. We argue that there is no need to invoke repeat types other than ARM repeats for a proper description of the structure of the p115 globular head region. Additionally, we propose to define a new subfamily of ARM-like proteins and show lack of evidence that the ARM motifs found in p115 are present in other long coiled-coil tethering factors of the golgin family.

  18. Exploiting publicly available biological and biochemical information for the discovery of novel short linear motifs.

    KAUST Repository

    Sayadi, Ahmed

    2011-07-20

    The function of proteins is often mediated by short linear segments of their amino acid sequence, called Short Linear Motifs or SLiMs, the identification of which can provide important information about a protein function. However, the short length of the motifs and their variable degree of conservation makes their identification hard since it is difficult to correctly estimate the statistical significance of their occurrence. Consequently, only a small fraction of them have been discovered so far. We describe here an approach for the discovery of SLiMs based on their occurrence in evolutionarily unrelated proteins belonging to the same biological, signalling or metabolic pathway and give specific examples of its effectiveness in both rediscovering known motifs and in discovering novel ones. An automatic implementation of the procedure, available for download, allows significant motifs to be identified, automatically annotated with functional, evolutionary and structural information and organized in a database that can be inspected and queried. An instance of the database populated with pre-computed data on seven organisms is accessible through a publicly available server and we believe it constitutes by itself a useful resource for the life sciences (http://www.biocomputing.it/modipath).

  19. An intracellular motif of GLUT4 regulates fusion of GLUT4-containing vesicles.

    Science.gov (United States)

    Heyward, Catherine A; Pettitt, Trevor R; Leney, Sophie E; Welsh, Gavin I; Tavaré, Jeremy M; Wakelam, Michael J O

    2008-05-20

    Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is not yet clear. Here we report the identification of a putative phosphatidic acid-binding motif in a GLUT4 intracellular loop. Mutation of this motif causes a decrease in the insulin-induced exposure of GLUT4 at the cell surface of 3T3-L1 adipocytes via an effect on vesicle fusion. The potential phosphatidic acid-binding motif identified in this study is unique to GLUT4 among the sugar transporters, therefore this motif may provide a unique mechanism for regulating insulin-induced translocation by phospholipase D signalling.

  20. Mutational analysis of the RecJ exonuclease of Escherichia coli: identification of phosphoesterase motifs.

    Science.gov (United States)

    Sutera, V A; Han, E S; Rajman, L A; Lovett, S T

    1999-10-01

    The recJ gene, identified in Escherichia coli, encodes a Mg(+2)-dependent 5'-to-3' exonuclease with high specificity for single-strand DNA. Genetic and biochemical experiments implicate RecJ exonuclease in homologous recombination, base excision, and methyl-directed mismatch repair. Genes encoding proteins with strong similarities to RecJ have been found in every eubacterial genome sequenced to date, with the exception of Mycoplasma and Mycobacterium tuberculosis. Multiple genes encoding proteins similar to RecJ are found in some eubacteria, including Bacillus and Helicobacter, and in the archaea. Among this divergent set of sequences, seven conserved motifs emerge. We demonstrate here that amino acids within six of these motifs are essential for both the biochemical and genetic functions of E. coli RecJ. These motifs may define interactions with Mg(2+) ions or substrate DNA. A large family of proteins more distantly related to RecJ is present in archaea, eubacteria, and eukaryotes, including a hypothetical protein in the MgPa adhesin operon of Mycoplasma, a domain of putative polyA polymerases in Synechocystis and Aquifex, PRUNE of Drosophila, and an exopolyphosphatase (PPX1) of Saccharomyces cereviseae. Because these six RecJ motifs are shared between exonucleases and exopolyphosphatases, they may constitute an ancient phosphoesterase domain now found in all kingdoms of life.

  1. On the origin of distribution patterns of motifs in biological networks

    Directory of Open Access Journals (Sweden)

    Lesk Arthur M

    2008-08-01

    Full Text Available Abstract Background Inventories of small subgraphs in biological networks have identified commonly-recurring patterns, called motifs. The inference that these motifs have been selected for function rests on the idea that their occurrences are significantly more frequent than random. Results Our analysis of several large biological networks suggests, in contrast, that the frequencies of appearance of common subgraphs are similar in natural and corresponding random networks. Conclusion Indeed, certain topological features of biological networks give rise naturally to the common appearance of the motifs. We therefore question whether frequencies of occurrences are reasonable evidence that the structures of motifs have been selected for their functional contribution to the operation of networks.

  2. An intracellular motif of GLUT4 regulates fusion of GLUT4-containing vesicles

    Directory of Open Access Journals (Sweden)

    Welsh Gavin I

    2008-05-01

    Full Text Available Abstract Background Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is not yet clear. Results Here we report the identification of a putative phosphatidic acid-binding motif in a GLUT4 intracellular loop. Mutation of this motif causes a decrease in the insulin-induced exposure of GLUT4 at the cell surface of 3T3-L1 adipocytes via an effect on vesicle fusion. Conclusion The potential phosphatidic acid-binding motif identified in this study is unique to GLUT4 among the sugar transporters, therefore this motif may provide a unique mechanism for regulating insulin-induced translocation by phospholipase D signalling.

  3. Preliminary phenomena identification and ranking tables for simplified boiling water reactor Loss-of-Coolant Accident scenarios

    International Nuclear Information System (INIS)

    Kroeger, P.G.; Rohatgi, U.S.; Jo, J.H.; Slovik, G.C.

    1998-04-01

    For three potential Loss-of-Coolant Accident (LOCA) scenarios in the General Electric Simplified Boiling Water Reactors (SBWR) a set of Phenomena Identification and Ranking Tables (PIRT) is presented. The selected LOCA scenarios are typical for the class of small and large breaks generally considered in Safety Analysis Reports. The method used to develop the PIRTs is described. Following is a discussion of the transient scenarios, the PIRTs are presented and discussed in detailed and in summarized form. A procedure for future validation of the PIRTs, to enhance their value, is outlined. 26 refs., 25 figs., 44 tabs

  4. Enrichment of Circular Code Motifs in the Genes of the Yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Christian J. Michel

    2017-12-01

    Full Text Available A set X of 20 trinucleotides has been found to have the highest average occurrence in the reading frame, compared to the two shifted frames, of genes of bacteria, archaea, eukaryotes, plasmids and viruses. This set X has an interesting mathematical property, since X is a maximal C 3 self-complementary trinucleotide circular code. Furthermore, any motif obtained from this circular code X has the capacity to retrieve, maintain and synchronize the original (reading frame. Since 1996, the theory of circular codes in genes has mainly been developed by analysing the properties of the 20 trinucleotides of X , using combinatorics and statistical approaches. For the first time, we test this theory by analysing the X motifs, i.e., motifs from the circular code X , in the complete genome of the yeast Saccharomyces cerevisiae. Several properties of X motifs are identified by basic statistics (at the frequency level, and evaluated by comparison to R motifs, i.e., random motifs generated from 30 different random codes R . We first show that the frequency of X motifs is significantly greater than that of R motifs in the genome of S. cerevisiae. We then verify that no significant difference is observed between the frequencies of X and R motifs in the non-coding regions of S. cerevisiae, but that the occurrence number of X motifs is significantly higher than R motifs in the genes (protein-coding regions. This property is true for all cardinalities of X motifs (from 4 to 20 and for all 16 chromosomes. We further investigate the distribution of X motifs in the three frames of S. cerevisiae genes and show that they occur more frequently in the reading frame, regardless of their cardinality or their length. Finally, the ratio of X genes, i.e., genes with at least one X motif, to non- X genes, in the set of verified genes is significantly different to that observed in the set of putative or dubious genes with no experimental evidence. These results, taken together

  5. Enrichment of Circular Code Motifs in the Genes of the Yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Michel, Christian J; Ngoune, Viviane Nguefack; Poch, Olivier; Ripp, Raymond; Thompson, Julie D

    2017-12-03

    A set X of 20 trinucleotides has been found to have the highest average occurrence in the reading frame, compared to the two shifted frames, of genes of bacteria, archaea, eukaryotes, plasmids and viruses. This set X has an interesting mathematical property, since X is a maximal C3 self-complementary trinucleotide circular code. Furthermore, any motif obtained from this circular code X has the capacity to retrieve, maintain and synchronize the original (reading) frame. Since 1996, the theory of circular codes in genes has mainly been developed by analysing the properties of the 20 trinucleotides of X, using combinatorics and statistical approaches. For the first time, we test this theory by analysing the X motifs, i.e., motifs from the circular code X, in the complete genome of the yeast Saccharomyces cerevisiae . Several properties of X motifs are identified by basic statistics (at the frequency level), and evaluated by comparison to R motifs, i.e., random motifs generated from 30 different random codes R. We first show that the frequency of X motifs is significantly greater than that of R motifs in the genome of S. cerevisiae . We then verify that no significant difference is observed between the frequencies of X and R motifs in the non-coding regions of S. cerevisiae , but that the occurrence number of X motifs is significantly higher than R motifs in the genes (protein-coding regions). This property is true for all cardinalities of X motifs (from 4 to 20) and for all 16 chromosomes. We further investigate the distribution of X motifs in the three frames of S. cerevisiae genes and show that they occur more frequently in the reading frame, regardless of their cardinality or their length. Finally, the ratio of X genes, i.e., genes with at least one X motif, to non-X genes, in the set of verified genes is significantly different to that observed in the set of putative or dubious genes with no experimental evidence. These results, taken together, represent the first

  6. Stepwise identification of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus type 1 genome boosted by a StepRank scheme.

    Science.gov (United States)

    Bi, Jianjun; Song, Rengang; Yang, Huilan; Li, Bingling; Fan, Jianyong; Liu, Zhongrong; Long, Chaoqin

    2011-01-01

    Identification of immunodominant epitopes is the first step in the rational design of peptide vaccines aimed at T-cell immunity. To date, however, it is yet a great challenge for accurately predicting the potent epitope peptides from a pool of large-scale candidates with an efficient manner. In this study, a method that we named StepRank has been developed for the reliable and rapid prediction of binding capabilities/affinities between proteins and genome-wide peptides. In this procedure, instead of single strategy used in most traditional epitope identification algorithms, four steps with different purposes and thus different computational demands are employed in turn to screen the large-scale peptide candidates that are normally generated from, for example, pathogenic genome. The steps 1 and 2 aim at qualitative exclusion of typical nonbinders by using empirical rule and linear statistical approach, while the steps 3 and 4 focus on quantitative examination and prediction of the interaction energy profile and binding affinity of peptide to target protein via quantitative structure-activity relationship (QSAR) and structure-based free energy analysis. We exemplify this method through its application to binding predictions of the peptide segments derived from the 76 known open-reading frames (ORFs) of herpes simplex virus type 1 (HSV-1) genome with or without affinity to human major histocompatibility complex class I (MHC I) molecule HLA-A*0201, and find that the predictive results are well compatible with the classical anchor residue theory and perfectly match for the extended motif pattern of MHC I-binding peptides. The putative epitopes are further confirmed by comparisons with 11 experimentally measured HLA-A*0201-restrcited peptides from the HSV-1 glycoproteins D and K. We expect that this well-designed scheme can be applied in the computational screening of other viral genomes as well.

  7. Evolutionary dynamics of a conserved sequence motif in the ribosomal genes of the ciliate Paramecium.

    Science.gov (United States)

    Catania, Francesco; Lynch, Michael

    2010-05-04

    In protozoa, the identification of preserved motifs by comparative genomics is often impeded by difficulties to generate reliable alignments for non-coding sequences. Moreover, the evolutionary dynamics of regulatory elements in 3' untranslated regions (both in protozoa and metazoa) remains a virtually unexplored issue. By screening Paramecium tetraurelia's 3' untranslated regions for 8-mers that were previously found to be preserved in mammalian 3' UTRs, we detect and characterize a motif that is distinctly conserved in the ribosomal genes of this ciliate. The motif appears to be conserved across Paramecium aurelia species but is absent from the ribosomal genes of four additional non-Paramecium species surveyed, including another ciliate, Tetrahymena thermophila. Motif-free ribosomal genes retain fewer paralogs in the genome and appear to be lost more rapidly relative to motif-containing genes. Features associated with the discovered preserved motif are consistent with this 8-mer playing a role in post-transcriptional regulation. Our observations 1) shed light on the evolution of a putative regulatory motif across large phylogenetic distances; 2) are expected to facilitate the understanding of the modulation of ribosomal genes expression in Paramecium; and 3) reveal a largely unexplored--and presumably not restricted to Paramecium--association between the presence/absence of a DNA motif and the evolutionary fate of its host genes.

  8. Automatic annotation of protein motif function with Gene Ontology terms

    Directory of Open Access Journals (Sweden)

    Gopalakrishnan Vanathi

    2004-09-01

    Full Text Available Abstract Background Conserved protein sequence motifs are short stretches of amino acid sequence patterns that potentially encode the function of proteins. Several sequence pattern searching algorithms and programs exist foridentifying candidate protein motifs at the whole genome level. However, amuch needed and importanttask is to determine the functions of the newly identified protein motifs. The Gene Ontology (GO project is an endeavor to annotate the function of genes or protein sequences with terms from a dynamic, controlled vocabulary and these annotations serve well as a knowledge base. Results This paperpresents methods to mine the GO knowledge base and use the association between the GO terms assigned to a sequence and the motifs matched by the same sequence as evidence for predicting the functions of novel protein motifs automatically. The task of assigning GO terms to protein motifsis viewed as both a binary classification and information retrieval problem, where PROSITE motifs are used as samples for mode training and functional prediction. The mutual information of a motif and aGO term association isfound to be a very useful feature. We take advantageof the known motifs to train a logistic regression classifier, which allows us to combine mutual information with other frequency-based features and obtain a probability of correctassociation. The trained logistic regression model has intuitively meaningful and logically plausible parameter values, and performs very well empirically according to our evaluation criteria. Conclusions In this research, different methods for automatic annotation of protein motifs have been investigated. Empirical result demonstrated that the methods have a great potential for detecting and augmenting information about thefunctions of newly discovered candidate protein motifs.

  9. Verification of the MOTIF code version 3.0

    International Nuclear Information System (INIS)

    Chan, T.; Guvanasen, V.; Nakka, B.W.; Reid, J.A.K.; Scheier, N.W.; Stanchell, F.W.

    1996-12-01

    As part of the Canadian Nuclear Fuel Waste Management Program (CNFWMP), AECL has developed a three-dimensional finite-element code, MOTIF (Model Of Transport In Fractured/ porous media), for detailed modelling of groundwater flow, heat transport and solute transport in a fractured rock mass. The code solves the transient and steady-state equations of groundwater flow, solute (including one-species radionuclide) transport, and heat transport in variably saturated fractured/porous media. The initial development was completed in 1985 (Guvanasen 1985) and version 3.0 was completed in 1986. This version is documented in detail in Guvanasen and Chan (in preparation). This report describes a series of fourteen verification cases which has been used to test the numerical solution techniques and coding of MOTIF, as well as demonstrate some of the MOTIF analysis capabilities. For each case the MOTIF solution has been compared with a corresponding analytical or independently developed alternate numerical solution. Several of the verification cases were included in Level 1 of the International Hydrologic Code Intercomparison Project (HYDROCOIN). The MOTIF results for these cases were also described in the HYDROCOIN Secretariat's compilation and comparison of results submitted by the various project teams (Swedish Nuclear Power Inspectorate 1988). It is evident from the graphical comparisons presented that the MOTIF solutions for the fourteen verification cases are generally in excellent agreement with known analytical or numerical solutions obtained from independent sources. This series of verification studies has established the ability of the MOTIF finite-element code to accurately model the groundwater flow and solute and heat transport phenomena for which it is intended. (author). 20 refs., 14 tabs., 32 figs

  10. RANK/RANKL/OPG Signalization Implication in Periodontitis: New Evidence from a RANK Transgenic Mouse Model

    Directory of Open Access Journals (Sweden)

    Bouchra Sojod

    2017-05-01

    Full Text Available Periodontitis is based on a complex inflammatory over-response combined with possible genetic predisposition factors. The RANKL/RANK/OPG signaling pathway is implicated in bone resorption through its key function in osteoclast differentiation and activation, as well as in the inflammatory response. This central element of osteo-immunology has been suggested to be perturbed in several diseases, including periodontitis, as it is a predisposing factor for this disease. The aim of the present study was to validate this hypothesis using a transgenic mouse line, which over-expresses RANK (RTg and develops a periodontitis-like phenotype at 5 months of age. RTg mice exhibited severe alveolar bone loss, an increased number of TRAP positive cells, and disorganization of periodontal ligaments. This phenotype was more pronounced in females. We also observed dental root resorption lacunas. Hyperplasia of the gingival epithelium, including Malassez epithelial rests, was visible as early as 25 days, preceding any other symptoms. These results demonstrate that perturbations of the RANKL/RANK/OPG system constitute a core element of periodontitis, and more globally, osteo-immune diseases.

  11. RANK/RANKL/OPG Signalization Implication in Periodontitis: New Evidence from a RANK Transgenic Mouse Model

    Science.gov (United States)

    Sojod, Bouchra; Chateau, Danielle; Mueller, Christopher G.; Babajko, Sylvie; Berdal, Ariane; Lézot, Frédéric; Castaneda, Beatriz

    2017-01-01

    Periodontitis is based on a complex inflammatory over-response combined with possible genetic predisposition factors. The RANKL/RANK/OPG signaling pathway is implicated in bone resorption through its key function in osteoclast differentiation and activation, as well as in the inflammatory response. This central element of osteo-immunology has been suggested to be perturbed in several diseases, including periodontitis, as it is a predisposing factor for this disease. The aim of the present study was to validate this hypothesis using a transgenic mouse line, which over-expresses RANK (RTg) and develops a periodontitis-like phenotype at 5 months of age. RTg mice exhibited severe alveolar bone loss, an increased number of TRAP positive cells, and disorganization of periodontal ligaments. This phenotype was more pronounced in females. We also observed dental root resorption lacunas. Hyperplasia of the gingival epithelium, including Malassez epithelial rests, was visible as early as 25 days, preceding any other symptoms. These results demonstrate that perturbations of the RANKL/RANK/OPG system constitute a core element of periodontitis, and more globally, osteo-immune diseases. PMID:28596739

  12. Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas

    Science.gov (United States)

    Petrov, Anton I.; Zirbel, Craig L.; Leontis, Neocles B.

    2013-01-01

    The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson–Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access. PMID:23970545

  13. Improved statistical signal detection in pharmacovigilance by combining multiple strength-of-evidence aspects in vigiRank.

    Science.gov (United States)

    Caster, Ola; Juhlin, Kristina; Watson, Sarah; Norén, G Niklas

    2014-08-01

    Detection of unknown risks with marketed medicines is key to securing the optimal care of individual patients and to reducing the societal burden from adverse drug reactions. Large collections of individual case reports remain the primary source of information and require effective analytics to guide clinical assessors towards likely drug safety signals. Disproportionality analysis is based solely on aggregate numbers of reports and naively disregards report quality and content. However, these latter features are the very fundament of the ensuing clinical assessment. Our objective was to develop and evaluate a data-driven screening algorithm for emerging drug safety signals that accounts for report quality and content. vigiRank is a predictive model for emerging safety signals, here implemented with shrinkage logistic regression to identify predictive variables and estimate their respective contributions. The variables considered for inclusion capture different aspects of strength of evidence, including quality and clinical content of individual reports, as well as trends in time and geographic spread. A reference set of 264 positive controls (historical safety signals from 2003 to 2007) and 5,280 negative controls (pairs of drugs and adverse events not listed in the Summary of Product Characteristics of that drug in 2012) was used for model fitting and evaluation; the latter used fivefold cross-validation to protect against over-fitting. All analyses were performed on a reconstructed version of VigiBase(®) as of 31 December 2004, at around which time most safety signals in our reference set were emerging. The following aspects of strength of evidence were selected for inclusion into vigiRank: the numbers of informative and recent reports, respectively; disproportional reporting; the number of reports with free-text descriptions of the case; and the geographic spread of reporting. vigiRank offered a statistically significant improvement in area under the receiver

  14. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data.

    Science.gov (United States)

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2014-02-20

    ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data.

  15. APOCALYPTIC MOTIFS IN THE CYCLE OF STORIES BY M.A. BULGAKOV «NOTES OF A YOUNG DOCTOR»

    Directory of Open Access Journals (Sweden)

    Evgeniy Igorevich Erokhov

    2015-10-01

    Full Text Available The motif analysis of a cycle of stories by M.A. Bulgakov «Notes of a Young Doctor» from the point of view of their apocalyptic problematics was first performed in this article. To identify apocalyptic motifs the method of motif analysis, developed by B.M. Gasparov, was used which will also help to prove the interpenetration of motifs in the cycle of stories. The result of the research work is the identification of apocalyptic motifs which are manifested in the experiences of the main character and the events taking place around him and passing through the prism of physician’s perception of the world. Our identified motifs show that the stories in the cycle are united not only thematically and with the help of the image of the main character, but with the help of the motifs which reflect interpenetration of apocalyptic motifs in the stories of one cycle. There are the following apocalyptic motifs in the cycle of stories by Bulgakov: diseases, darkness (as part of the landscape, resurrection from the dead and beast. They all belong to the biblical type which is allocated on the basis of the associative bond of these motifs with the biblical texts.

  16. Ranking in evolving complex networks

    Science.gov (United States)

    Liao, Hao; Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng; Zhou, Ming-Yang

    2017-05-01

    Complex networks have emerged as a simple yet powerful framework to represent and analyze a wide range of complex systems. The problem of ranking the nodes and the edges in complex networks is critical for a broad range of real-world problems because it affects how we access online information and products, how success and talent are evaluated in human activities, and how scarce resources are allocated by companies and policymakers, among others. This calls for a deep understanding of how existing ranking algorithms perform, and which are their possible biases that may impair their effectiveness. Many popular ranking algorithms (such as Google's PageRank) are static in nature and, as a consequence, they exhibit important shortcomings when applied to real networks that rapidly evolve in time. At the same time, recent advances in the understanding and modeling of evolving networks have enabled the development of a wide and diverse range of ranking algorithms that take the temporal dimension into account. The aim of this review is to survey the existing ranking algorithms, both static and time-aware, and their applications to evolving networks. We emphasize both the impact of network evolution on well-established static algorithms and the benefits from including the temporal dimension for tasks such as prediction of network traffic, prediction of future links, and identification of significant nodes.

  17. Evolutionary dynamics of a conserved sequence motif in the ribosomal genes of the ciliate Paramecium

    Directory of Open Access Journals (Sweden)

    Lynch Michael

    2010-05-01

    Full Text Available Abstract Background In protozoa, the identification of preserved motifs by comparative genomics is often impeded by difficulties to generate reliable alignments for non-coding sequences. Moreover, the evolutionary dynamics of regulatory elements in 3' untranslated regions (both in protozoa and metazoa remains a virtually unexplored issue. Results By screening Paramecium tetraurelia's 3' untranslated regions for 8-mers that were previously found to be preserved in mammalian 3' UTRs, we detect and characterize a motif that is distinctly conserved in the ribosomal genes of this ciliate. The motif appears to be conserved across Paramecium aurelia species but is absent from the ribosomal genes of four additional non-Paramecium species surveyed, including another ciliate, Tetrahymena thermophila. Motif-free ribosomal genes retain fewer paralogs in the genome and appear to be lost more rapidly relative to motif-containing genes. Features associated with the discovered preserved motif are consistent with this 8-mer playing a role in post-transcriptional regulation. Conclusions Our observations 1 shed light on the evolution of a putative regulatory motif across large phylogenetic distances; 2 are expected to facilitate the understanding of the modulation of ribosomal genes expression in Paramecium; and 3 reveal a largely unexplored--and presumably not restricted to Paramecium--association between the presence/absence of a DNA motif and the evolutionary fate of its host genes.

  18. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs

    OpenAIRE

    Chang, Tzu-Hao; Huang, Hsi-Yuan; Hsu, Justin Bo-Kai; Weng, Shun-Long; Horng, Jorng-Tzong; Huang, Hsien-Da

    2013-01-01

    Background Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform. Methods ...

  19. A proposed vestigial translation initiation motif in VP1 of hepatitis A virus.

    Science.gov (United States)

    Kang, Jeong-Ah; Funkhouser, Ann W

    2002-07-01

    The internal ribosome entry site (IRES) of picornaviruses has a 3' polypyrimidine tract (PPT) 16-24 bases upstream of an AUG triplet (PPT/AUG motif). This motif is critical in determining the efficiency of cap-independent translation. HAV has a conserved PPT/AUG motif consisting of a nine base sequence (AGGUUUUUC) 23 bases upstream of the preferred AUG start codon. This HAV-specific PPT/AUG motif is repeated and conserved in VP1 of HAV, but not of other picornaviruses. We proposed that the PPT/AUG motif in the open reading frame initiated translation and/or had an impact on the life cycle of the virus. In vitro translation of mutant bicistronic mRNAs and growth in cell culture of mutant viruses provided no evidence that the VP1 PPT/AUG motif had any impact on either translation or growth. HAV differs from other picornaviruses in its inefficient growth in cell culture. Since the HAV-specific PPT/AUG motif is found in only 1 in 300,000 reported viral sequences outside the hepatovirus genus, this motif may be a vestigial translation initiation element and may have played a role in determining the unusual phenotype of HAV.

  20. How pathogens use linear motifs to perturb host cell networks

    KAUST Repository

    Via, Allegra; Uyar, Bora; Brun, Christine; Zanzoni, Andreas

    2015-01-01

    Molecular mimicry is one of the powerful stratagems that pathogens employ to colonise their hosts and take advantage of host cell functions to guarantee their replication and dissemination. In particular, several viruses have evolved the ability to interact with host cell components through protein short linear motifs (SLiMs) that mimic host SLiMs, thus facilitating their internalisation and the manipulation of a wide range of cellular networks. Here we present convincing evidence from the literature that motif mimicry also represents an effective, widespread hijacking strategy in prokaryotic and eukaryotic parasites. Further insights into host motif mimicry would be of great help in the elucidation of the molecular mechanisms behind host cell invasion and the development of anti-infective therapeutic strategies.

  1. Identification of novel conserved functional motifs across most Influenza A viral strains

    Directory of Open Access Journals (Sweden)

    El-Azab Iman

    2011-01-01

    Full Text Available Abstract Background Influenza A virus poses a continuous threat to global public health. Design of novel universal drugs and vaccine requires a careful analysis of different strains of Influenza A viral genome from diverse hosts and subtypes. We performed a systematic in silico analysis of Influenza A viral segments of all available Influenza A viral strains and subtypes and grouped them based on host, subtype, and years isolated, and through multiple sequence alignments we extrapolated conserved regions, motifs, and accessible regions for functional mapping and annotation. Results Across all species and strains 87 highly conserved regions (conservation percentage > = 90% and 19 functional motifs (conservation percentage = 100% were found in PB2, PB1, PA, NP, M, and NS segments. The conservation percentage of these segments ranged between 94 - 98% in human strains (the most conserved, 85 - 93% in swine strains (the most variable, and 91 - 94% in avian strains. The most conserved segment was different in each host (PB1 for human strains, NS for avian strains, and M for swine strains. Target accessibility prediction yielded 324 accessible regions, with a single stranded probability > 0.5, of which 78 coincided with conserved regions. Some of the interesting annotations in these regions included sites for protein-protein interactions, the RNA binding groove, and the proton ion channel. Conclusions The influenza virus has evolved to adapt to its host through variations in the GC content and conservation percentage of the conserved regions. Nineteen universal conserved functional motifs were discovered, of which some were accessible regions with interesting biological functions. These regions will serve as a foundation for universal drug targets as well as universal vaccine design.

  2. Comprehensive Identification of Glycated Peptides and Their Glycation Motifs in Plasma and Erythrocytes of Control and Diabetic Subjects

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Monroe, Matthew E.; Schepmoes, Athena A.; Clauss, Therese RW; Gritsenko, Marina A.; Meng, Da; Petyuk, Vladislav A.; Smith, Richard D.; Metz, Thomas O.

    2011-07-01

    Non-enzymatic glycation of proteins is implicated in diabetes mellitus and its related complications. In this report, we extend our previous development and refinement of proteomics-based methods for the analysis of non-enzymatically glycated proteins to comprehensively identify glycated proteins in normal and diabetic human plasma and erythrocytes. Using immunodepletion, enrichment, and fractionation strategies, we identified 7749 unique glycated peptides, corresponding to 3742 unique glycated proteins. Semi-quantitative comparisons revealed a number of proteins with glycation levels significantly increased in diabetes relative to control samples and that erythrocyte proteins are more extensively glycated than plasma proteins. A glycation motif analysis revealed amino acids that are favored more than others in the protein primary structures in the vicinity of the glycation sites in both sample types. The glycated peptides and corresponding proteins reported here provide a foundation for the potential identification of novel markers for diabetes, glycemia, or diabetic complications.

  3. Low Rank Approximation Algorithms, Implementation, Applications

    CERN Document Server

    Markovsky, Ivan

    2012-01-01

    Matrix low-rank approximation is intimately related to data modelling; a problem that arises frequently in many different fields. Low Rank Approximation: Algorithms, Implementation, Applications is a comprehensive exposition of the theory, algorithms, and applications of structured low-rank approximation. Local optimization methods and effective suboptimal convex relaxations for Toeplitz, Hankel, and Sylvester structured problems are presented. A major part of the text is devoted to application of the theory. Applications described include: system and control theory: approximate realization, model reduction, output error, and errors-in-variables identification; signal processing: harmonic retrieval, sum-of-damped exponentials, finite impulse response modeling, and array processing; machine learning: multidimensional scaling and recommender system; computer vision: algebraic curve fitting and fundamental matrix estimation; bioinformatics for microarray data analysis; chemometrics for multivariate calibration; ...

  4. Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets.

    Science.gov (United States)

    Chiu, Yi-Yuan; Lin, Chun-Yu; Lin, Chih-Ta; Hsu, Kai-Cheng; Chang, Li-Zen; Yang, Jinn-Moon

    2012-01-01

    To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery.

  5. Estimating error rates for firearm evidence identifications in forensic science

    Science.gov (United States)

    Song, John; Vorburger, Theodore V.; Chu, Wei; Yen, James; Soons, Johannes A.; Ott, Daniel B.; Zhang, Nien Fan

    2018-01-01

    Estimating error rates for firearm evidence identification is a fundamental challenge in forensic science. This paper describes the recently developed congruent matching cells (CMC) method for image comparisons, its application to firearm evidence identification, and its usage and initial tests for error rate estimation. The CMC method divides compared topography images into correlation cells. Four identification parameters are defined for quantifying both the topography similarity of the correlated cell pairs and the pattern congruency of the registered cell locations. A declared match requires a significant number of CMCs, i.e., cell pairs that meet all similarity and congruency requirements. Initial testing on breech face impressions of a set of 40 cartridge cases fired with consecutively manufactured pistol slides showed wide separation between the distributions of CMC numbers observed for known matching and known non-matching image pairs. Another test on 95 cartridge cases from a different set of slides manufactured by the same process also yielded widely separated distributions. The test results were used to develop two statistical models for the probability mass function of CMC correlation scores. The models were applied to develop a framework for estimating cumulative false positive and false negative error rates and individual error rates of declared matches and non-matches for this population of breech face impressions. The prospect for applying the models to large populations and realistic case work is also discussed. The CMC method can provide a statistical foundation for estimating error rates in firearm evidence identifications, thus emulating methods used for forensic identification of DNA evidence. PMID:29331680

  6. Genome-wide identification of basic helix-loop-helix and NF-1 motifs underlying GR binding sites in male rat hippocampus

    DEFF Research Database (Denmark)

    Pooley, John R.; Flynn, Ben P.; Grøntved, Lars

    2017-01-01

    linked to structural and organizational roles, an absence of major tethering partners for GRs, and little or no evidence for binding at negative glucocorticoid response elements. A basic helix-loop-helix motif closely resembling a NeuroD1 or Olig2 binding site was found underlying a subset of GR binding......Glucocorticoids regulate hippocampal function in part by modulating gene expression through the glucocorticoid receptor (GR). GR binding is highly cell type specific, directed to accessible chromatin regions established during tissue differentiation. Distinct classes of GR binding sites...

  7. Exploiting publicly available biological and biochemical information for the discovery of novel short linear motifs.

    KAUST Repository

    Sayadi, Ahmed; Briganti, Leonardo; Tramontano, Anna; Via, Allegra

    2011-01-01

    The function of proteins is often mediated by short linear segments of their amino acid sequence, called Short Linear Motifs or SLiMs, the identification of which can provide important information about a protein function. However, the short length

  8. Insights into the motif preference of APOBEC3 enzymes.

    Directory of Open Access Journals (Sweden)

    Diako Ebrahimi

    Full Text Available We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome.

  9. Advanced Neutron Source Reactor (ANSR) phenomena identification and ranking (PIR) for large break loss of coolant accidents (LBLOCA)

    International Nuclear Information System (INIS)

    Ruggles, A.E.; Cheng, L.Y.; Dimenna, R.A.; Griffith, P.; Wilson, G.E.

    1994-06-01

    A team of experts in reactor analysis conducted a phenomena identification and ranking (PIR) exercise for a large break loss-of-coolant accident (LBLOCA) in the Advanced Neutron source Reactor (ANSR). The LBLOCA transient is broken into two separate parts for the PIR exercise. The first part considers the initial depressurization of the system that follows the opening of the break. The second part of the transient includes long-term decay heat removal after the reactor is shut down and the system is depressurized. A PIR is developed for each part of the LBLOCA. The ranking results are reviewed to establish if models in the RELAP5-MOD3 thermalhydraulic code are adequate for use in ANSR LBLOCA simulations. Deficiencies in the RELAP5-MOD3 code are identified and existing data or models are recommended to improve the code for this application. Experiments were also suggested to establish models for situations judged to be beyond current knowledge. The applicability of the ANSR PIR results is reviewed for the entire set of transients important to the ANSR safety analysis

  10. Charting taxonomic knowledge through ontologies and ranking algorithms

    Science.gov (United States)

    Huber, Robert; Klump, Jens

    2009-04-01

    Since the inception of geology as a modern science, paleontologists have described a large number of fossil species. This makes fossilized organisms an important tool in the study of stratigraphy and past environments. Since taxonomic classifications of organisms, and thereby their names, change frequently, the correct application of this tool requires taxonomic expertise in finding correct synonyms for a given species name. Much of this taxonomic information has already been published in journals and books where it is compiled in carefully prepared synonymy lists. Because this information is scattered throughout the paleontological literature, it is difficult to find and sometimes not accessible. Also, taxonomic information in the literature is often difficult to interpret for non-taxonomists looking for taxonomic synonymies as part of their research. The highly formalized structure makes Open Nomenclature synonymy lists ideally suited for computer aided identification of taxonomic synonyms. Because a synonymy list is a list of citations related to a taxon name, its bibliographic nature allows the application of bibliometric techniques to calculate the impact of synonymies and taxonomic concepts. TaxonRank is a ranking algorithm based on bibliometric analysis and Internet page ranking algorithms. TaxonRank uses published synonymy list data stored in TaxonConcept, a taxonomic information system. The basic ranking algorithm has been modified to include a measure of confidence on species identification based on the Open Nomenclature notation used in synonymy list, as well as other synonymy specific criteria. The results of our experiments show that the output of the proposed ranking algorithm gives a good estimate of the impact a published taxonomic concept has on the taxonomic opinions in the geological community. Also, our results show that treating taxonomic synonymies as part of on an ontology is a way to record and manage taxonomic knowledge, and thus contribute

  11. Visual Antipriming Effect: Evidence from Chinese Character Identification

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-10-01

    Full Text Available Marsolek et al. (2006 have differentiated antipriming effects from priming effects, by adopting a novel priming paradigm comprised of four phases that include a baseline measurement. The general concept of antipriming supports the overlapping representation theory of knowledge. This study extended examination of the Marsolek et al. (2006 paradigm by investigating antipriming and priming effects in a series of Chinese character identification tasks. Results showed that identification accuracy of old characters was significantly higher than baseline measurements (i.e., the priming effect, while identification accuracy of novel characters was significantly lower than baseline measurements (i.e., the antipriming effect. This study demonstrates for the first time the effect of visual antipriming in Chinese character identification. It further provides new evidence for the overlapping representation theory of knowledge, and supports generalizability of the phenomenon to Chinese characters.

  12. LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms.

    Science.gov (United States)

    Yang, Peng; Wu, Min; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

    2014-02-17

    As a fundamental genomic element, meiotic recombination hotspot plays important roles in life sciences. Thus uncovering its regulatory mechanisms has broad impact on biomedical research. Despite the recent identification of the zinc finger protein PRDM9 and its 13-mer binding motif as major regulators for meiotic recombination hotspots, other regulators remain to be discovered. Existing methods for finding DNA sequence motifs of recombination hotspots often rely on the enrichment of co-localizations between hotspots and short DNA patterns, which ignore the cross-individual variation of recombination rates and sequence polymorphisms in the population. Our objective in this paper is to capture signals encoded in genetic variations for the discovery of recombination-associated DNA motifs. Recently, an algorithm called "LDsplit" has been designed to detect the association between single nucleotide polymorphisms (SNPs) and proximal meiotic recombination hotspots. The association is measured by the difference of population recombination rates at a hotspot between two alleles of a candidate SNP. Here we present an open source software tool of LDsplit, with integrative data visualization for recombination hotspots and their proximal SNPs. Applying LDsplit on SNPs inside an established 7-mer motif bound by PRDM9 we observed that SNP alleles preserving the original motif tend to have higher recombination rates than the opposite alleles that disrupt the motif. Running on SNP windows around hotspots each containing an occurrence of the 7-mer motif, LDsplit is able to guide the established motif finding algorithm of MEME to recover the 7-mer motif. In contrast, without LDsplit the 7-mer motif could not be identified. LDsplit is a software tool for the discovery of cis-regulatory DNA sequence motifs stimulating meiotic recombination hotspots by screening and narrowing down to hotspot associated SNPs. It is the first computational method that utilizes the genetic variation of

  13. Identification of high-efficiency 3′GG gRNA motifs in indexed FASTA files with ngg2

    Directory of Open Access Journals (Sweden)

    Elisha D. Roberson

    2015-11-01

    Full Text Available CRISPR/Cas9 is emerging as one of the most-used methods of genome modification in organisms ranging from bacteria to human cells. However, the efficiency of editing varies tremendously site-to-site. A recent report identified a novel motif, called the 3′GG motif, which substantially increases the efficiency of editing at all sites tested in C. elegans. Furthermore, they highlighted that previously published gRNAs with high editing efficiency also had this motif. I designed a Python command-line tool, ngg2, to identify 3′GG gRNA sites from indexed FASTA files. As a proof-of-concept, I screened for these motifs in six model genomes: Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, and Homo sapiens. I also scanned the genomes of pig (Sus scrofa and African elephant (Loxodonta africana to demonstrate the utility in non-model organisms. I identified more than 60 million single match 3′GG motifs in these genomes. Greater than 61% of all protein coding genes in the reference genomes had at least one unique 3′GG gRNA site overlapping an exon. In particular, more than 96% of mouse and 93% of human protein coding genes have at least one unique, overlapping 3′GG gRNA. These identified sites can be used as a starting point in gRNA selection, and the ngg2 tool provides an important ability to identify 3′GG editing sites in any species with an available genome sequence.

  14. The MHC motif viewer: a visualization tool for MHC binding motifs

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Hoof, Ilka; Lund, Ole

    2010-01-01

    is hampered by the lack of tools for browsing and comparing specificity of these molecules. We have developed a Web server, MHC Motif Viewer, which allows the display of the binding motif for MHC class I proteins for human, chimpanzee, rhesus monkey, mouse, and swine, as well as HLA-DR protein sequences...

  15. Adiabatic quantum algorithm for search engine ranking.

    Science.gov (United States)

    Garnerone, Silvano; Zanardi, Paolo; Lidar, Daniel A

    2012-06-08

    We propose an adiabatic quantum algorithm for generating a quantum pure state encoding of the PageRank vector, the most widely used tool in ranking the relative importance of internet pages. We present extensive numerical simulations which provide evidence that this algorithm can prepare the quantum PageRank state in a time which, on average, scales polylogarithmically in the number of web pages. We argue that the main topological feature of the underlying web graph allowing for such a scaling is the out-degree distribution. The top-ranked log(n) entries of the quantum PageRank state can then be estimated with a polynomial quantum speed-up. Moreover, the quantum PageRank state can be used in "q-sampling" protocols for testing properties of distributions, which require exponentially fewer measurements than all classical schemes designed for the same task. This can be used to decide whether to run a classical update of the PageRank.

  16. Equal opportunity for low-degree network nodes: a PageRank-based method for protein target identification in metabolic graphs.

    Directory of Open Access Journals (Sweden)

    Dániel Bánky

    Full Text Available Biological network data, such as metabolic-, signaling- or physical interaction graphs of proteins are increasingly available in public repositories for important species. Tools for the quantitative analysis of these networks are being developed today. Protein network-based drug target identification methods usually return protein hubs with large degrees in the networks as potentially important targets. Some known, important protein targets, however, are not hubs at all, and perturbing protein hubs in these networks may have several unwanted physiological effects, due to their interaction with numerous partners. Here, we show a novel method applicable in networks with directed edges (such as metabolic networks that compensates for the low degree (non-hub vertices in the network, and identifies important nodes, regardless of their hub properties. Our method computes the PageRank for the nodes of the network, and divides the PageRank by the in-degree (i.e., the number of incoming edges of the node. This quotient is the same in all nodes in an undirected graph (even for large- and low-degree nodes, that is, for hubs and non-hubs as well, but may differ significantly from node to node in directed graphs. We suggest to assign importance to non-hub nodes with large PageRank/in-degree quotient. Consequently, our method gives high scores to nodes with large PageRank, relative to their degrees: therefore non-hub important nodes can easily be identified in large networks. We demonstrate that these relatively high PageRank scores have biological relevance: the method correctly finds numerous already validated drug targets in distinct organisms (Mycobacterium tuberculosis, Plasmodium falciparum and MRSA Staphylococcus aureus, and consequently, it may suggest new possible protein targets as well. Additionally, our scoring method was not chosen arbitrarily: its value for all nodes of all undirected graphs is constant; therefore its high value captures

  17. Equal opportunity for low-degree network nodes: a PageRank-based method for protein target identification in metabolic graphs.

    Science.gov (United States)

    Bánky, Dániel; Iván, Gábor; Grolmusz, Vince

    2013-01-01

    Biological network data, such as metabolic-, signaling- or physical interaction graphs of proteins are increasingly available in public repositories for important species. Tools for the quantitative analysis of these networks are being developed today. Protein network-based drug target identification methods usually return protein hubs with large degrees in the networks as potentially important targets. Some known, important protein targets, however, are not hubs at all, and perturbing protein hubs in these networks may have several unwanted physiological effects, due to their interaction with numerous partners. Here, we show a novel method applicable in networks with directed edges (such as metabolic networks) that compensates for the low degree (non-hub) vertices in the network, and identifies important nodes, regardless of their hub properties. Our method computes the PageRank for the nodes of the network, and divides the PageRank by the in-degree (i.e., the number of incoming edges) of the node. This quotient is the same in all nodes in an undirected graph (even for large- and low-degree nodes, that is, for hubs and non-hubs as well), but may differ significantly from node to node in directed graphs. We suggest to assign importance to non-hub nodes with large PageRank/in-degree quotient. Consequently, our method gives high scores to nodes with large PageRank, relative to their degrees: therefore non-hub important nodes can easily be identified in large networks. We demonstrate that these relatively high PageRank scores have biological relevance: the method correctly finds numerous already validated drug targets in distinct organisms (Mycobacterium tuberculosis, Plasmodium falciparum and MRSA Staphylococcus aureus), and consequently, it may suggest new possible protein targets as well. Additionally, our scoring method was not chosen arbitrarily: its value for all nodes of all undirected graphs is constant; therefore its high value captures importance in the

  18. Development of a preliminary PIRT (Phenomena Identification and Ranking Table) of thermal-hydraulic phenomena for SMART

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Bub Dong; Lee, Won Jae; Kim, Hee Cheol; Song, Jin Ho; Sim, Suk Ku [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1998-12-31

    The work reported in this paper identifies the thermal-hydraulic phenomena that are expected to occur during a number of key transients in SMART (System-integrated Modular Advanced ReacTor) which is under development at KAERI. The result of this effort is based on the current design concept of SMART integral reactor. Although the design is still evolving, the preliminary Phenomena Identification and Ranking Table (PIRT) has been developed based on the experts` knowledge and experience. The preliminary PIRT has been developed by consensus of KAERI expert panelists and AHP (Analytical Hierarchy Process). Preliminary PIRT developed in this paper is intended to be used to identify and integrate development areas of further experimental tests needed, thermal hydraulic models and correlations and code improvements for the safety analysis of the SMART. 8 refs., 4 tabs (Author)

  19. Development of a preliminary PIRT (Phenomena Identification and Ranking Table) of thermal-hydraulic phenomena for SMART

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Bub Dong; Lee, Won Jae; Kim, Hee Cheol; Song, Jin Ho; Sim, Suk Ku [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1997-12-31

    The work reported in this paper identifies the thermal-hydraulic phenomena that are expected to occur during a number of key transients in SMART (System-integrated Modular Advanced ReacTor) which is under development at KAERI. The result of this effort is based on the current design concept of SMART integral reactor. Although the design is still evolving, the preliminary Phenomena Identification and Ranking Table (PIRT) has been developed based on the experts` knowledge and experience. The preliminary PIRT has been developed by consensus of KAERI expert panelists and AHP (Analytical Hierarchy Process). Preliminary PIRT developed in this paper is intended to be used to identify and integrate development areas of further experimental tests needed, thermal hydraulic models and correlations and code improvements for the safety analysis of the SMART. 8 refs., 4 tabs (Author)

  20. Kopi dan Kakao dalam Kreasi Motif Batik Khas Jember

    Directory of Open Access Journals (Sweden)

    Irfa'ina Rohana Salma

    2015-06-01

    Full Text Available ABSTRAK Batik Jember selama ini identik dengan motif daun tembakau. Visualisasi daun tembakau dalam motif Batik Jember cukup lemah, yaitu kurang berkarakter karena motif yang muncul adalah seperti gambar daun pada umumnya. Oleh karena itu perlu diciptakan desain motif batik khas Jember yang sumber inspirasinya digali dari kekayaan alam lainnya dari Jember yang mempunyai bentuk spesifik dan karakteristik sehingga identitas motif bisa didapatkan dengan lebih kuat. Hasil alam khas Jember tersebut adalah kopi dan kakao. Tujuan penciptaan seni ini adalah untuk menghasilkan motif batik  baru yang mempunyai ciri khas Jember. Metode yang digunakan yaitu pengumpulan data, pengamatan mendalam terhadap objek penciptaan, pengkajian sumber inspirasi, pembuatan desain motif, dan perwujudan menjadi batik. Dari penciptaan seni ini berhasil dikreasikan 6 (enam motif batik yaitu: (1 Motif Uwoh Kopi; (2 Motif Godong Kopi;  (3 Motif Ceplok Kakao; (4 Motif Kakao Raja; (5 Motif Kakao Biru; dan (6 Motif Wiji Mukti. Berdasarkan hasil penilaian “Selera Estetika” diketahui bahwa motif yang paling banyak disukai adalah Motif Uwoh Kopi dan Motif Kakao Raja. Kata kunci: Motif Woh Kopi, Motif Godong Kopi, Motif Ceplok Kakao, Motif Kakao Raja, Motif Kakao Biru, Motif Wiji Mukti ABSTRACTBatik Jember is synonymous with tobacco leaf motif. Tobacco leaf shape is quite weak in the visual appearance characterized as that motif emerges like a picture of leaves in general. Therefore, it is necessary to create a distinctive design motif extracted from other natural resources of Jember that have specific shapes and characteristics that can be obtained as the stronger motif identity. The typical natural resources from Jember are coffee and cocoa. The purpose of the creation of this art is to produce the unique, creative and innovative batik and have specific characteristics of Jember. The method used are data collection, observation of the object, reviewing inspiration sources

  1. An improved rank based disease prediction using web navigation patterns on bio-medical databases

    Directory of Open Access Journals (Sweden)

    P. Dhanalakshmi

    2017-12-01

    Full Text Available Applying machine learning techniques to on-line biomedical databases is a challenging task, as this data is collected from large number of sources and it is multi-dimensional. Also retrieval of relevant document from large repository such as gene document takes more processing time and an increased false positive rate. Generally, the extraction of biomedical document is based on the stream of prior observations of gene parameters taken at different time periods. Traditional web usage models such as Markov, Bayesian and Clustering models are sensitive to analyze the user navigation patterns and session identification in online biomedical database. Moreover, most of the document ranking models on biomedical database are sensitive to sparsity and outliers. In this paper, a novel user recommendation system was implemented to predict the top ranked biomedical documents using the disease type, gene entities and user navigation patterns. In this recommendation system, dynamic session identification, dynamic user identification and document ranking techniques were used to extract the highly relevant disease documents on the online PubMed repository. To verify the performance of the proposed model, the true positive rate and runtime of the model was compared with that of traditional static models such as Bayesian and Fuzzy rank. Experimental results show that the performance of the proposed ranking model is better than the traditional models.

  2. Co-integration Rank Testing under Conditional Heteroskedasticity

    DEFF Research Database (Denmark)

    Cavaliere, Guiseppe; Rahbæk, Anders; Taylor, A.M. Robert

    null distributions of the rank statistics coincide with those derived by previous authors who assume either i.i.d. or (strict and covariance) stationary martingale difference innovations. We then propose wild bootstrap implementations of the co-integrating rank tests and demonstrate that the associated...... bootstrap rank statistics replicate the first-order asymptotic null distributions of the rank statistics. We show the same is also true of the corresponding rank tests based on the i.i.d. bootstrap of Swensen (2006). The wild bootstrap, however, has the important property that, unlike the i.i.d. bootstrap......, it preserves in the re-sampled data the pattern of heteroskedasticity present in the original shocks. Consistent with this, numerical evidence sug- gests that, relative to tests based on the asymptotic critical values or the i.i.d. bootstrap, the wild bootstrap rank tests perform very well in small samples un...

  3. CombiMotif: A new algorithm for network motifs discovery in protein-protein interaction networks

    Science.gov (United States)

    Luo, Jiawei; Li, Guanghui; Song, Dan; Liang, Cheng

    2014-12-01

    Discovering motifs in protein-protein interaction networks is becoming a current major challenge in computational biology, since the distribution of the number of network motifs can reveal significant systemic differences among species. However, this task can be computationally expensive because of the involvement of graph isomorphic detection. In this paper, we present a new algorithm (CombiMotif) that incorporates combinatorial techniques to count non-induced occurrences of subgraph topologies in the form of trees. The efficiency of our algorithm is demonstrated by comparing the obtained results with the current state-of-the art subgraph counting algorithms. We also show major differences between unicellular and multicellular organisms. The datasets and source code of CombiMotif are freely available upon request.

  4. MSDmotif: exploring protein sites and motifs

    Directory of Open Access Journals (Sweden)

    Henrick Kim

    2008-07-01

    Full Text Available Abstract Background Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure. Results We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS protocol. An additional entry point facilitates XML requests with XML responses. Conclusion MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures.

  5. The Verrucomicrobia LexA-binding Motif: Insights into the Evolutionary Dynamics of the SOS Response

    Directory of Open Access Journals (Sweden)

    Ivan Erill

    2016-07-01

    Full Text Available The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls.

  6. The Verrucomicrobia LexA-Binding Motif: Insights into the Evolutionary Dynamics of the SOS Response.

    Science.gov (United States)

    Erill, Ivan; Campoy, Susana; Kılıç, Sefa; Barbé, Jordi

    2016-01-01

    The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division, and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls.

  7. Statistical tests to compare motif count exceptionalities

    Directory of Open Access Journals (Sweden)

    Vandewalle Vincent

    2007-03-01

    Full Text Available Abstract Background Finding over- or under-represented motifs in biological sequences is now a common task in genomics. Thanks to p-value calculation for motif counts, exceptional motifs are identified and represent candidate functional motifs. The present work addresses the related question of comparing the exceptionality of one motif in two different sequences. Just comparing the motif count p-values in each sequence is indeed not sufficient to decide if this motif is significantly more exceptional in one sequence compared to the other one. A statistical test is required. Results We develop and analyze two statistical tests, an exact binomial one and an asymptotic likelihood ratio test, to decide whether the exceptionality of a given motif is equivalent or significantly different in two sequences of interest. For that purpose, motif occurrences are modeled by Poisson processes, with a special care for overlapping motifs. Both tests can take the sequence compositions into account. As an illustration, we compare the octamer exceptionalities in the Escherichia coli K-12 backbone versus variable strain-specific loops. Conclusion The exact binomial test is particularly adapted for small counts. For large counts, we advise to use the likelihood ratio test which is asymptotic but strongly correlated with the exact binomial test and very simple to use.

  8. Identification of Top-ranked Proteins within a Directional Protein Interaction Network using the PageRank Algorithm: Applications in Humans and Plants.

    Science.gov (United States)

    Li, Xiu-Qing; Xing, Tim; Du, Donglei

    2016-01-01

    Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.

  9. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, Susan, E-mail: S.Gibbs@VUMC.nl [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Corsini, Emanuela [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Spiekstra, Sander W. [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Galbiati, Valentina [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Fuchs, Horst W. [CellSystems GmbH, Troisdorf (Germany); DeGeorge, George; Troese, Matthew [MB Research Labs, Spinnerstown, PA (United States); Hayden, Patrick; Deng, Wei [MatTek Corporation, Ashland, MA (United States); Roggen, Erwin [3Rs Management and Consultancy (Denmark)

    2013-10-15

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC{sub 50}) with human and animal data showed a superior correlation with human DSA{sub 05} (μg/cm{sup 2}) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA{sub 05} = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA{sub 05} data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency

  10. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    International Nuclear Information System (INIS)

    Gibbs, Susan; Corsini, Emanuela; Spiekstra, Sander W.; Galbiati, Valentina; Fuchs, Horst W.; DeGeorge, George; Troese, Matthew; Hayden, Patrick; Deng, Wei; Roggen, Erwin

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC 50 ) with human and animal data showed a superior correlation with human DSA 05 (μg/cm 2 ) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA 05 = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA 05 data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency • EC50 (chemical

  11. Identity and functions of CxxC-derived motifs.

    Science.gov (United States)

    Fomenko, Dmitri E; Gladyshev, Vadim N

    2003-09-30

    Two cysteines separated by two other residues (the CxxC motif) are employed by many redox proteins for formation, isomerization, and reduction of disulfide bonds and for other redox functions. The place of the C-terminal cysteine in this motif may be occupied by serine (the CxxS motif), modifying the functional repertoire of redox proteins. Here we found that the CxxC motif may also give rise to a motif, in which the C-terminal cysteine is replaced with threonine (the CxxT motif). Moreover, in contrast to a view that the N-terminal cysteine in the CxxC motif always serves as a nucleophilic attacking group, this residue could also be replaced with threonine (the TxxC motif), serine (the SxxC motif), or other residues. In each of these CxxC-derived motifs, the presence of a downstream alpha-helix was strongly favored. A search for conserved CxxC-derived motif/helix patterns in four complete genomes representing bacteria, archaea, and eukaryotes identified known redox proteins and suggested possible redox functions for several additional proteins. Catalytic sites in peroxiredoxins were major representatives of the TxxC motif, whereas those in glutathione peroxidases represented the CxxT motif. Structural assessments indicated that threonines in these enzymes could stabilize catalytic thiolates, suggesting revisions to previously proposed catalytic triads. Each of the CxxC-derived motifs was also observed in natural selenium-containing proteins, in which selenocysteine was present in place of a catalytic cysteine.

  12. Motif decomposition of the phosphotyrosine proteome reveals a new N-terminal binding motif for SHIP2

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Hanke, S.; Hinsby, A. M.

    2008-01-01

    set of 481 unique phosphotyrosine (Tyr(P)) peptides by sequence similarity to known ligands of the Src homology 2 (SH2) and the phosphotyrosine binding (PTB) domains. From 20 clusters we extracted 16 known and four new interaction motifs. Using quantitative mass spectrometry we pulled down Tyr......(P)-specific binding partners for peptides corresponding to the extracted motifs. We confirmed numerous previously known interaction motifs and found 15 new interactions mediated by phosphosites not previously known to bind SH2 or PTB. Remarkably, a novel hydrophobic N-terminal motif ((L/V/I)(L/V/I)pY) was identified...

  13. [Personal motif in art].

    Science.gov (United States)

    Gerevich, József

    2015-01-01

    One of the basic questions of the art psychology is whether a personal motif is to be found behind works of art and if so, how openly or indirectly it appears in the work itself. Analysis of examples and documents from the fine arts and literature allow us to conclude that the personal motif that can be identified by the viewer through symbols, at times easily at others with more difficulty, gives an emotional plus to the artistic product. The personal motif may be found in traumatic experiences, in communication to the model or with other emotionally important persons (mourning, disappointment, revenge, hatred, rivalry, revolt etc.), in self-searching, or self-analysis. The emotions are expressed in artistic activity either directly or indirectly. The intention nourished by the artist's identity (Kunstwollen) may stand in the way of spontaneous self-expression, channelling it into hidden paths. Under the influence of certain circumstances, the artist may arouse in the viewer, consciously or unconsciously, an illusionary, misleading image of himself. An examination of the personal motif is one of the important research areas of art therapy.

  14. Evidence based guidelines for the prevention, identification, and management of occupational asthma.

    Science.gov (United States)

    Nicholson, P J; Cullinan, P; Taylor, A J Newman; Burge, P S; Boyle, C

    2005-05-01

    Occupational asthma is the most frequently reported work related respiratory disease in many countries. This work was commissioned by the British Occupational Health Research Foundation to assist the Health and Safety Executive in achieving its target of reducing the incidence of occupational asthma in Great Britain by 30% by 2010. The guidelines aim to improve the prevention, identification, and management of occupational asthma by providing evidence based recommendations on which future practice can be based. The literature was searched systematically using Medline and Embase for articles published in all languages up to the end of June 2004. Evidence based statements and recommendations were graded according to the Royal College of General Practitioner's star system and the revised Scottish Intercollegiate Guidelines Network grading system. A total of 474 original studies were selected for appraisal from over 2500 abstracts. The systematic review produced 52 graded evidence statements and 22 recommendations based on 223 studies. Evidence based guidelines have become benchmarks for practice in healthcare and the process used to prepare them is well established. This evidence review and its recommendations focus on interventions and outcomes to provide a robust approach to the prevention, identification, and management of occupational asthma, based on and using the best available medical evidence. The most important action to prevent cases of occupational asthma is to reduce exposure at source. Thereafter surveillance should be performed for the early identification of symptoms, including occupational rhinitis, with additional functional and immunological tests where appropriate. Effective management of workers suspected to have occupational asthma involves the identification and investigation of symptoms suggestive of asthma immediately they occur. Those workers who are confirmed to have occupational asthma should be advised to avoid further exposure completely

  15. Temporal motifs in time-dependent networks

    International Nuclear Information System (INIS)

    Kovanen, Lauri; Karsai, Márton; Kaski, Kimmo; Kertész, János; Saramäki, Jari

    2011-01-01

    Temporal networks are commonly used to represent systems where connections between elements are active only for restricted periods of time, such as telecommunication, neural signal processing, biochemical reaction and human social interaction networks. We introduce the framework of temporal motifs to study the mesoscale topological–temporal structure of temporal networks in which the events of nodes do not overlap in time. Temporal motifs are classes of similar event sequences, where the similarity refers not only to topology but also to the temporal order of the events. We provide a mapping from event sequences to coloured directed graphs that enables an efficient algorithm for identifying temporal motifs. We discuss some aspects of temporal motifs, including causality and null models, and present basic statistics of temporal motifs in a large mobile call network

  16. Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria.

    Science.gov (United States)

    Sun, Eric I; Leyn, Semen A; Kazanov, Marat D; Saier, Milton H; Novichkov, Pavel S; Rodionov, Dmitry A

    2013-09-02

    In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis. A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations. The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome

  17. Motif enrichment tool.

    Science.gov (United States)

    Blatti, Charles; Sinha, Saurabh

    2014-07-01

    The Motif Enrichment Tool (MET) provides an online interface that enables users to find major transcriptional regulators of their gene sets of interest. MET searches the appropriate regulatory region around each gene and identifies which transcription factor DNA-binding specificities (motifs) are statistically overrepresented. Motif enrichment analysis is currently available for many metazoan species including human, mouse, fruit fly, planaria and flowering plants. MET also leverages high-throughput experimental data such as ChIP-seq and DNase-seq from ENCODE and ModENCODE to identify the regulatory targets of a transcription factor with greater precision. The results from MET are produced in real time and are linked to a genome browser for easy follow-up analysis. Use of the web tool is free and open to all, and there is no login requirement. ADDRESS: http://veda.cs.uiuc.edu/MET/. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Identification, occurrence, and validation of DRE and ABRE Cis-regulatory motifs in the promoter regions of genes of Arabidopsis thaliana.

    Science.gov (United States)

    Mishra, Sonal; Shukla, Aparna; Upadhyay, Swati; Sanchita; Sharma, Pooja; Singh, Seema; Phukan, Ujjal J; Meena, Abha; Khan, Feroz; Tripathi, Vineeta; Shukla, Rakesh Kumar; Shrama, Ashok

    2014-04-01

    Plants posses a complex co-regulatory network which helps them to elicit a response under diverse adverse conditions. We used an in silico approach to identify the genes with both DRE and ABRE motifs in their promoter regions in Arabidopsis thaliana. Our results showed that Arabidopsis contains a set of 2,052 genes with ABRE and DRE motifs in their promoter regions. Approximately 72% or more of the total predicted 2,052 genes had a gap distance of less than 400 bp between DRE and ABRE motifs. For positional orientation of the DRE and ABRE motifs, we found that the DR form (one in direct and the other one in reverse orientation) was more prevalent than other forms. These predicted 2,052 genes include 155 transcription factors. Using microarray data from The Arabidopsis Information Resource (TAIR) database, we present 44 transcription factors out of 155 which are upregulated by more than twofold in response to osmotic stress and ABA treatment. Fifty-one transcripts from the one predicted above were validated using semiquantitative expression analysis to support the microarray data in TAIR. Taken together, we report a set of genes containing both DRE and ABRE motifs in their promoter regions in A. thaliana, which can be useful to understand the role of ABA under osmotic stress condition. © 2013 Institute of Botany, Chinese Academy of Sciences.

  19. KIRMES: kernel-based identification of regulatory modules in euchromatic sequences.

    Science.gov (United States)

    Schultheiss, Sebastian J; Busch, Wolfgang; Lohmann, Jan U; Kohlbacher, Oliver; Rätsch, Gunnar

    2009-08-15

    Understanding transcriptional regulation is one of the main challenges in computational biology. An important problem is the identification of transcription factor (TF) binding sites in promoter regions of potential TF target genes. It is typically approached by position weight matrix-based motif identification algorithms using Gibbs sampling, or heuristics to extend seed oligos. Such algorithms succeed in identifying single, relatively well-conserved binding sites, but tend to fail when it comes to the identification of combinations of several degenerate binding sites, as those often found in cis-regulatory modules. We propose a new algorithm that combines the benefits of existing motif finding with the ones of support vector machines (SVMs) to find degenerate motifs in order to improve the modeling of regulatory modules. In experiments on microarray data from Arabidopsis thaliana, we were able to show that the newly developed strategy significantly improves the recognition of TF targets. The python source code (open source-licensed under GPL), the data for the experiments and a Galaxy-based web service are available at http://www.fml.mpg.de/raetsch/suppl/kirmes/.

  20. Motif-Independent De Novo Detection of Secondary Metabolite Gene Clusters – Towards Identification of Novel Secondary Metabolisms from Filamentous Fungi -

    Directory of Open Access Journals (Sweden)

    Myco eUmemura

    2015-05-01

    Full Text Available Secondary metabolites are produced mostly by clustered genes that are essential to their biosynthesis. The transcriptional expression of these genes is often cooperatively regulated by a transcription factor located inside or close to a cluster. Most of the secondary metabolism biosynthesis (SMB gene clusters identified to date contain so-called core genes with distinctive sequence features, such as polyketide synthase (PKS and non-ribosomal peptide synthetase (NRPS. Recent efforts in sequencing fungal genomes have revealed far more SMB gene clusters than expected based on the number of core genes in the genomes. Several bioinformatics tools have been developed to survey SMB gene clusters using the sequence motif information of the core genes, including SMURF and antiSMASH.More recently, accompanied by the development of sequencing techniques allowing to obtain large-scale genomic and transcriptomic data, motif-independent prediction methods of SMB gene clusters, including MIDDAS-M, have been developed. Most these methods detect the clusters in which the genes are cooperatively regulated at transcriptional levels, thus allowing the identification of novel SMB gene clusters regardless of the presence of the core genes. Another type of the method, MIPS-CG, uses the characteristics of SMB genes, which are highly enriched in non-syntenic blocks (NSBs, enabling the prediction even without transcriptome data although the results have not been evaluated in detail. Considering that large portion of SMB gene clusters might be sufficiently expressed only in limited uncommon conditions, it seems that prediction of SMB gene clusters by bioinformatics and successive experimental validation is an only way to efficiently uncover hidden SMB gene clusters. Here, we describe and discuss possible novel approaches for the determination of SMB gene clusters that have not been identified using conventional methods.

  1. Rank Dynamics

    Science.gov (United States)

    Gershenson, Carlos

    Studies of rank distributions have been popular for decades, especially since the work of Zipf. For example, if we rank words of a given language by use frequency (most used word in English is 'the', rank 1; second most common word is 'of', rank 2), the distribution can be approximated roughly with a power law. The same applies for cities (most populated city in a country ranks first), earthquakes, metabolism, the Internet, and dozens of other phenomena. We recently proposed ``rank diversity'' to measure how ranks change in time, using the Google Books Ngram dataset. Studying six languages between 1800 and 2009, we found that the rank diversity curves of languages are universal, adjusted with a sigmoid on log-normal scale. We are studying several other datasets (sports, economies, social systems, urban systems, earthquakes, artificial life). Rank diversity seems to be universal, independently of the shape of the rank distribution. I will present our work in progress towards a general description of the features of rank change in time, along with simple models which reproduce it

  2. PageRank tracker: from ranking to tracking.

    Science.gov (United States)

    Gong, Chen; Fu, Keren; Loza, Artur; Wu, Qiang; Liu, Jia; Yang, Jie

    2014-06-01

    Video object tracking is widely used in many real-world applications, and it has been extensively studied for over two decades. However, tracking robustness is still an issue in most existing methods, due to the difficulties with adaptation to environmental or target changes. In order to improve adaptability, this paper formulates the tracking process as a ranking problem, and the PageRank algorithm, which is a well-known webpage ranking algorithm used by Google, is applied. Labeled and unlabeled samples in tracking application are analogous to query webpages and the webpages to be ranked, respectively. Therefore, determining the target is equivalent to finding the unlabeled sample that is the most associated with existing labeled set. We modify the conventional PageRank algorithm in three aspects for tracking application, including graph construction, PageRank vector acquisition and target filtering. Our simulations with the use of various challenging public-domain video sequences reveal that the proposed PageRank tracker outperforms mean-shift tracker, co-tracker, semiboosting and beyond semiboosting trackers in terms of accuracy, robustness and stability.

  3. Computerized Dental Comparison: A Critical Review of Dental Coding and Ranking Algorithms Used in Victim Identification.

    Science.gov (United States)

    Adams, Bradley J; Aschheim, Kenneth W

    2016-01-01

    Comparison of antemortem and postmortem dental records is a leading method of victim identification, especially for incidents involving a large number of decedents. This process may be expedited with computer software that provides a ranked list of best possible matches. This study provides a comparison of the most commonly used conventional coding and sorting algorithms used in the United States (WinID3) with a simplified coding format that utilizes an optimized sorting algorithm. The simplified system consists of seven basic codes and utilizes an optimized algorithm based largely on the percentage of matches. To perform this research, a large reference database of approximately 50,000 antemortem and postmortem records was created. For most disaster scenarios, the proposed simplified codes, paired with the optimized algorithm, performed better than WinID3 which uses more complex codes. The detailed coding system does show better performance with extremely large numbers of records and/or significant body fragmentation. © 2015 American Academy of Forensic Sciences.

  4. UKIRAN KERAWANG ACEH GAYO SEBAGAI INSPIRASI PENCIPTAAN MOTIF BATIK KHAS GAYO

    Directory of Open Access Journals (Sweden)

    Irfa ina Rohana Salma

    2016-12-01

    Full Text Available ABSTRAK Industri batik mulai berkembang di Gayo, tetapi belum memiliki motif batik khas daerah. Oleh karena itu perlu diciptakan motif batik khas Gayo, dengan mengambil inspirasi dari ukiran yang terdapat pada rumah tradisional yang biasa disebut ukiran kerawang Gayo. Tujuan penciptaan seni ini adalah untuk menciptakan motif batik yang memiliki ciri khas Gayo. Metode yang digunakan yaitu eksplorasi ide, perancangan, dan perwujudan menjadi motif batik. Dalam kegiatan ini telah diciptakan enam motif batik khas Gayo yaitu: (1 Motif Ceplok Gayo; (2 Motif Gayo Tegak; (3 Motif Gayo Lurus; (4 Motif Parang Gayo; (5 Motif Gayo Lembut; dan (6 Motif Geometris Gayo. Hasil uji kesukaan terhadap motif kepada lima puluh responden menunjukkan bahwa Motif Ceplok Gayo paling banyak dipilih oleh responden yaitu sebesar 19%, sedangkan Motif Parang Gayo 18%, Motif Gayo Lembut 17%, Motif Geometris Gayo 17%, Motif Gayo Lurus 15% dan Motif Gayo Tegak 14%. Rata-rata motif yang dihasilkan mendapatkan apresiasi yang baik dari responden, sehingga semua motif layak diproduksi sebagai batik khas Gayo.Kata kunci: batik Gayo, Motif Ceplok Gayo, Motif Parang Gayo.ABSTRACTBatik industry began to develop in Gayo, but have not had a typical batik motif itself. Therefore, it is necessary to create batik motifs of Gayo, by taking inspiration from the carvings found in traditional houses commonly called kerawang Gayo. The purpose of this art is to create motifs those have a Gayo characteristic. The method used are the idea exploration, design, and motifs embodiment. In this activity has created six Gayo batik motifs, namely: (1 Motif Ceplok Gayo; (2 Motif Gayo Tegak; (3 Motif GayoLurus; (4 Motif Parang Gayo; (5 Motif Gayo Lembut; dan (6 Motif Geometris Gayo. The test results fondness of the motives to fifty respondents indicated that the Motif Ceplok Gayo most preferred by respondents ie 19%, while Motif Parang Gayo 18%, Motif Gayo Lembut 17%, Motif Geometris Gayo 17%, Motif Gayo

  5. Identification of a novel calcium binding motif based on the detection of sequence insertions in the animal peroxidase domain of bacterial proteins.

    Science.gov (United States)

    Santamaría-Hernando, Saray; Krell, Tino; Ramos-González, María-Isabel

    2012-01-01

    Proteins of the animal heme peroxidase (ANP) superfamily differ greatly in size since they have either one or two catalytic domains that match profile PS50292. The orf PP_2561 of Pseudomonas putida KT2440 that we have called PepA encodes a two-domain ANP. The alignment of these domains with those of PepA homologues revealed a variable number of insertions with the consensus G-x-D-G-x-x-[GN]-[TN]-x-D-D. This motif has also been detected in the structure of pseudopilin (pdb 3G20), where it was found to be involved in Ca(2+) coordination although a sequence analysis did not reveal the presence of any known calcium binding motifs in this protein. Isothermal titration calorimetry revealed that a peptide containing this consensus motif bound specifically calcium ions with affinities ranging between 33-79 µM depending on the pH. Microcalorimetric titrations of the purified N-terminal ANP-like domain of PepA revealed Ca(2+) binding with a K(D) of 12 µM and stoichiometry of 1.25 calcium ions per protein monomer. This domain exhibited peroxidase activity after its reconstitution with heme. These data led to the definition of a novel calcium binding motif that we have termed PERCAL and which was abundantly present in animal peroxidase-like domains of bacterial proteins. Bacterial heme peroxidases thus possess two different types of calcium binding motifs, namely PERCAL and the related hemolysin type calcium binding motif, with the latter being located outside the catalytic domains and in their C-terminal end. A phylogenetic tree of ANP-like catalytic domains of bacterial proteins with PERCAL motifs, including single domain peroxidases, was divided into two major clusters, representing domains with and without PERCAL motif containing insertions. We have verified that the recently reported classification of bacterial heme peroxidases in two families (cd09819 and cd09821) is unrelated to these insertions. Sequences matching PERCAL were detected in all kingdoms of life.

  6. Identification of a novel calcium binding motif based on the detection of sequence insertions in the animal peroxidase domain of bacterial proteins.

    Directory of Open Access Journals (Sweden)

    Saray Santamaría-Hernando

    Full Text Available Proteins of the animal heme peroxidase (ANP superfamily differ greatly in size since they have either one or two catalytic domains that match profile PS50292. The orf PP_2561 of Pseudomonas putida KT2440 that we have called PepA encodes a two-domain ANP. The alignment of these domains with those of PepA homologues revealed a variable number of insertions with the consensus G-x-D-G-x-x-[GN]-[TN]-x-D-D. This motif has also been detected in the structure of pseudopilin (pdb 3G20, where it was found to be involved in Ca(2+ coordination although a sequence analysis did not reveal the presence of any known calcium binding motifs in this protein. Isothermal titration calorimetry revealed that a peptide containing this consensus motif bound specifically calcium ions with affinities ranging between 33-79 µM depending on the pH. Microcalorimetric titrations of the purified N-terminal ANP-like domain of PepA revealed Ca(2+ binding with a K(D of 12 µM and stoichiometry of 1.25 calcium ions per protein monomer. This domain exhibited peroxidase activity after its reconstitution with heme. These data led to the definition of a novel calcium binding motif that we have termed PERCAL and which was abundantly present in animal peroxidase-like domains of bacterial proteins. Bacterial heme peroxidases thus possess two different types of calcium binding motifs, namely PERCAL and the related hemolysin type calcium binding motif, with the latter being located outside the catalytic domains and in their C-terminal end. A phylogenetic tree of ANP-like catalytic domains of bacterial proteins with PERCAL motifs, including single domain peroxidases, was divided into two major clusters, representing domains with and without PERCAL motif containing insertions. We have verified that the recently reported classification of bacterial heme peroxidases in two families (cd09819 and cd09821 is unrelated to these insertions. Sequences matching PERCAL were detected in all kingdoms of

  7. Toward an Economic Mobility Ranking of U.S. Colleges. Evidence Speaks Reports, Vol 1, #6

    Science.gov (United States)

    Chingos, Matthew M.; Blagg, Kristin

    2015-01-01

    The release of institution-level earnings information as part of the Obama Administration's new College Scorecard data has already spawned new "value-added" rankings based on the economic outcomes of students who attended similar institutions. These emerging rankings are an improvement on simple unadjusted rankings, but the wide variance…

  8. A VLSI Implementation of Rank-Order Searching Circuit Employing a Time-Domain Technique

    Directory of Open Access Journals (Sweden)

    Trong-Tu Bui

    2013-01-01

    Full Text Available We present a compact and low-power rank-order searching (ROS circuit that can be used for building associative memories and rank-order filters (ROFs by employing time-domain computation and floating-gate MOS techniques. The architecture inherits the accuracy and programmability of digital implementations as well as the compactness and low-power consumption of analog ones. We aim to implement identification function as the first priority objective. Filtering function would be implemented once the location identification function has been carried out. The prototype circuit was designed and fabricated in a 0.18 μm CMOS technology. It consumes only 132.3 μW for an eight-input demonstration case.

  9. Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif

    Science.gov (United States)

    Shchedrina, Valentina A.; Novoselov, Sergey V.; Malinouski, Mikalai Yu.; Gladyshev, Vadim N.

    2007-01-01

    Selenocysteine (Sec, U) insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element. Selenoproteins with known functions are oxidoreductases containing a single redox-active Sec in their active sites. In this work, we identified a family of selenoproteins, designated SelL, containing two Sec separated by two other residues to form a UxxU motif. SelL proteins show an unusual occurrence, being present in diverse aquatic organisms, including fish, invertebrates, and marine bacteria. Both eukaryotic and bacterial SelL genes use single SECIS elements for insertion of two Sec. In eukaryotes, the SECIS is located in the 3′ UTR, whereas the bacterial SelL SECIS is within a coding region and positioned at a distance that supports the insertion of either of the two Sec or both of these residues. SelL proteins possess a thioredoxin-like fold wherein the UxxU motif corresponds to the catalytic CxxC motif in thioredoxins, suggesting a redox function of SelL proteins. Distantly related SelL-like proteins were also identified in a variety of organisms that had either one or both Sec replaced with Cys. Danio rerio SelL, transiently expressed in mammalian cells, incorporated two Sec and localized to the cytosol. In these cells, it occurred in an oxidized form and was not reducible by DTT. In a bacterial expression system, we directly demonstrated the formation of a diselenide bond between the two Sec, establishing it as the first diselenide bond found in a natural protein. PMID:17715293

  10. Dental Evidence in Forensic Identification – An Overview, Methodology and Present Status

    Science.gov (United States)

    Krishan, Kewal; Kanchan, Tanuj; Garg, Arun K

    2015-01-01

    Forensic odontology is primarily concerned with the use of teeth and oral structures for identification in a legal context. Various forensic odontology techniques help in the identification of the human remains in incidents such as terrorists’ attacks, airplane, train and road accidents, fires, mass murders, and natural disasters such as tsunamis, earth quakes and floods, etc. (Disaster Victim Identification-DVI). Dental structures are the hardest and well protected structures in the body. These structures resist decomposition and high temperatures and are among the last ones to disintegrate after death. The principal basis of the dental identification lies in the fact that no two oral cavities are alike and the teeth are unique to an individual. The dental evidence of the deceased recovered from the scene of crime/occurrence is compared with the ante-mortem records for identification. Dental features such as tooth morphology, variations in shape and size, restorations, pathologies, missing tooth, wear patterns, crowding of the teeth, colour and position of the tooth, rotations and other peculiar dental anomalies give every individual a unique identity. In absence of ante-mortem dental records for comparison, the teeth can help in the determination of age, sex, race/ethnicity, habits, occupations, etc. which can give further clues regarding the identity of the individuals. This piece of writing gives an overview of dental evidence, its use in forensic identification and its limitations. PMID:26312096

  11. Codon based co-occurrence network motifs in human mitochondria

    Directory of Open Access Journals (Sweden)

    Pramod Shinde

    2017-10-01

    Full Text Available The nucleotide polymorphism in human mitochondrial genome (mtDNA tolled by codon position bias plays an indispensable role in human population dispersion and expansion. Herein, we constructed genome-wide nucleotide co-occurrence networks using a massive data consisting of five different geographical regions and around 3000 samples for each region. We developed a powerful network model to describe complex mitochondrial evolutionary patterns between codon and non-codon positions. It was interesting to report a different evolution of Asian genomes than those of the rest which is divulged by network motifs. We found evidence that mtDNA undergoes substantial amounts of adaptive evolution, a finding which was supported by a number of previous studies. The dominance of higher order motifs indicated the importance of long-range nucleotide co-occurrence in genomic diversity. Most notably, codon motifs apparently underpinned the preferences among codon positions for co-evolution which is probably highly biased during the origin of the genetic code. Our analyses manifested that codon position co-evolution is very well conserved across human sub-populations and independently maintained within human sub-populations implying the selective role of evolutionary processes on codon position co-evolution. Ergo, this study provided a framework to investigate cooperative genomic interactions which are critical in underlying complex mitochondrial evolution.

  12. A sialoreceptor binding motif in the Mycoplasma synoviae adhesin VlhA.

    Directory of Open Access Journals (Sweden)

    Meghan May

    Full Text Available Mycoplasma synoviae depends on its adhesin VlhA to mediate cytadherence to sialylated host cell receptors. Allelic variants of VlhA arise through recombination between an assemblage of promoterless vlhA pseudogenes and a single transcription promoter site, creating lineages of M. synoviae that each express a different vlhA allele. The predicted full-length VlhA sequences adjacent to the promoter of nine lineages of M. synoviae varying in avidity of cytadherence were aligned with that of the reference strain MS53 and with a 60-a.a. hemagglutinating VlhA C-terminal fragment from a Tunisian lineage of strain WVU1853(T. Seven different sequence variants of an imperfectly conserved, single-copy, 12-a.a. candidate cytadherence motif were evident amid the flanking variable residues of the 11 total sequences examined. The motif was predicted to adopt a short hairpin structure in a low-complexity region near the C-terminus of VlhA. Biotinylated synthetic oligopeptides representing four selected variants of the 12-a.a. motif, with the whole synthesized 60-a.a. fragment as a positive control, differed (P<0.01 in the extent they bound to chicken erythrocyte membranes. All bound to a greater extent (P<0.01 than scrambled or irrelevant VlhA domain negative control peptides did. Experimentally introduced branched-chain amino acid (BCAA substitutions Val3Ile and Leu7Ile did not significantly alter binding, whereas fold-destabilizing substitutions Thr4Gly and Ala9Gly tended to reduce it (P<0.05. Binding was also reduced to background levels (P<0.01 when the peptides were exposed to desialylated membranes, or were pre-saturated with free sialic acid before exposure to untreated membranes. From this evidence we conclude that the motif P-X-(BCAA-X-F-X-(BCAA-X-A-K-X-G binds sialic acid and likely mediates VlhA-dependent M. synoviae attachment to host cells. This conserved mechanism retains the potential for fine-scale rheostasis in binding avidity, which could be a

  13. Social class rank, essentialism, and punitive judgment.

    Science.gov (United States)

    Kraus, Michael W; Keltner, Dacher

    2013-08-01

    Recent evidence suggests that perceptions of social class rank influence a variety of social cognitive tendencies, from patterns of causal attribution to moral judgment. In the present studies we tested the hypotheses that upper-class rank individuals would be more likely to endorse essentialist lay theories of social class categories (i.e., that social class is founded in genetically based, biological differences) than would lower-class rank individuals and that these beliefs would decrease support for restorative justice--which seeks to rehabilitate offenders, rather than punish unlawful action. Across studies, higher social class rank was associated with increased essentialism of social class categories (Studies 1, 2, and 4) and decreased support for restorative justice (Study 4). Moreover, manipulated essentialist beliefs decreased preferences for restorative justice (Study 3), and the association between social class rank and class-based essentialist theories was explained by the tendency to endorse beliefs in a just world (Study 2). Implications for how class-based essentialist beliefs potentially constrain social opportunity and mobility are discussed.

  14. Perception Enhancement using Visual Attributes in Sequence Motif Visualization

    OpenAIRE

    Oon, Yin; Lee, Nung; Kok, Wei

    2016-01-01

    Sequence logo is a well-accepted scientific method to visualize the conservation characteristics of biological sequence motifs. Previous studies found that using sequence logo graphical representation for scientific evidence reports or arguments could seriously cause biases and misinterpretation by users. This study investigates on the visual attributes performance of a sequence logo in helping users to perceive and interpret the information based on preattentive theories and Gestalt principl...

  15. MHC motif viewer

    DEFF Research Database (Denmark)

    Rapin, Nicolas Philippe Jean-Pierre; Hoof, Ilka; Lund, Ole

    2008-01-01

    . Algorithms that predict which peptides MHC molecules bind have recently been developed and cover many different alleles, but the utility of these algorithms is hampered by the lack of tools for browsing and comparing the specificity of these molecules. We have, therefore, developed a web server, MHC motif....... A special viewing feature, MHC fight, allows for display of the specificity of two different MHC molecules side by side. We show how the web server can be used to discover and display surprising similarities as well as differences between MHC molecules within and between different species. The MHC motif...

  16. 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.

  17. Deciphering functional glycosaminoglycan motifs in development.

    Science.gov (United States)

    Townley, Robert A; Bülow, Hannes E

    2018-03-23

    Glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate are linear glycans, which when attached to protein backbones form proteoglycans. GAGs are essential components of the extracellular space in metazoans. Extensive modifications of the glycans such as sulfation, deacetylation and epimerization create structural GAG motifs. These motifs regulate protein-protein interactions and are thereby repsonsible for many of the essential functions of GAGs. This review focusses on recent genetic approaches to characterize GAG motifs and their function in defined signaling pathways during development. We discuss a coding approach for GAGs that would enable computational analyses of GAG sequences such as alignments and the computation of position weight matrices to describe GAG motifs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Utilizing elements of the CSAU phenomena identification and ranking table (PIRT) to qualify a PWR non-LOCA transients system code

    Energy Technology Data Exchange (ETDEWEB)

    Greene, K.R.; Fletcher, C.D.; Gottula, R.C.; Lindquist, T.R.; Stitt, B.D. [Framatome ANP, Richland, WA (United States)

    2001-07-01

    Licensing analyses of Nuclear Regulatory Commission (NRC) Standard Review Plan (SRP) Chapter 15 non-LOCA transients are an important part of establishing operational safety limits and design limits for nuclear power plants. The applied codes and methods are generally qualified using traditional methods of benchmarking and assessment, sample problems, and demonstration of conservatism. Rigorous formal methods for developing code and methodology have been created and applied to qualify realistic methods for Large Break Loss-of-Coolant Accidents (LBLOCA's). This methodology, Code Scaling, Applicability, and Uncertainty (CSAU), is a very demanding, resource intensive, process to apply. It would be challenging to apply a comprehensive and complete CSAU level of analysis, individually, to each of the more than 30 non-LOCA transients that comprise Chapter 15 events. However, certain elements of the process can be easily adapted to improve quality of the codes and methods used to analyze non- LOCA transients. One of these elements is the Phenomena Identification and Ranking Table (PIRT). This paper presents the results of an informally constructed PIRT that applies to non-LOCA transients for Pressurized Water Reactors (PWR's) of the Westinghouse and Combustion Engineering design. A group of experts in thermal-hydraulics and safety analysis identified and ranked the phenomena. To begin the process, the PIRT was initially performed individually by each expert. Then through group interaction and discussion, a consensus was reached on both the significant phenomena and the appropriate ranking. The paper also discusses using the PIRT as an aid to qualify a 'conservative' system code and methodology. Once agreement was obtained on the phenomena and ranking, the table was divided into six functional groups, by nature of the transients, along the same lines as Chapter 15. Then, assessment and disposition of the significant phenomena was performed. The PIRT and

  19. Fitness for synchronization of network motifs

    DEFF Research Database (Denmark)

    Vega, Y.M.; Vázquez-Prada, M.; Pacheco, A.F.

    2004-01-01

    We study the synchronization of Kuramoto's oscillators in small parts of networks known as motifs. We first report on the system dynamics for the case of a scale-free network and show the existence of a non-trivial critical point. We compute the probability that network motifs synchronize, and fi...... that the fitness for synchronization correlates well with motifs interconnectedness and structural complexity. Possible implications for present debates about network evolution in biological and other systems are discussed....

  20. Multiple TPR motifs characterize the Fanconi anemia FANCG protein.

    Science.gov (United States)

    Blom, Eric; van de Vrugt, Henri J; de Vries, Yne; de Winter, Johan P; Arwert, Fré; Joenje, Hans

    2004-01-05

    The genome protection pathway that is defective in patients with Fanconi anemia (FA) is controlled by at least eight genes, including BRCA2. A key step in the pathway involves the monoubiquitylation of FANCD2, which critically depends on a multi-subunit nuclear 'core complex' of at least six FANC proteins (FANCA, -C, -E, -F, -G, and -L). Except for FANCL, which has WD40 repeats and a RING finger domain, no significant domain structure has so far been recognized in any of the core complex proteins. By using a homology search strategy comparing the human FANCG protein sequence with its ortholog sequences in Oryzias latipes (Japanese rice fish) and Danio rerio (zebrafish) we identified at least seven tetratricopeptide repeat motifs (TPRs) covering a major part of this protein. TPRs are degenerate 34-amino acid repeat motifs which function as scaffolds mediating protein-protein interactions, often found in multiprotein complexes. In four out of five TPR motifs tested (TPR1, -2, -5, and -6), targeted missense mutagenesis disrupting the motifs at the critical position 8 of each TPR caused complete or partial loss of FANCG function. Loss of function was evident from failure of the mutant proteins to complement the cellular FA phenotype in FA-G lymphoblasts, which was correlated with loss of binding to FANCA. Although the TPR4 mutant fully complemented the cells, it showed a reduced interaction with FANCA, suggesting that this TPR may also be of functional importance. The recognition of FANCG as a typical TPR protein predicts this protein to play a key role in the assembly and/or stabilization of the nuclear FA protein core complex.

  1. Aplikasi Ornamen Khas Maluku untuk Pengembangan Desain Motif Batik

    Directory of Open Access Journals (Sweden)

    Masiswo Masiswo

    2016-04-01

    Full Text Available ABSTRAKMaluku memiliki banyak ragam hias budaya warisan nilai leluhur berupa ornamen etnis yang merupakan kesenian dan keterampilan kerajinan. Hasil warisan tersebut sampai saat ini masih lestari hidup serta dapat dinikmati sebagai konsumsi rohani yang memuaskan manusia. Berkaitan dengan keberlangsungan nilai-nilai tradisi etnis yang berwujud pada ornamen-ornamen daerah Maluku, maka dikembangkan untuk kebutuhan manusia berupa motif batik pada kain. Pengembangan ornamen ini lebih menekankan pada representasi akan bentuk-bentuk ornamen yang diterapkan pada kerajinan batik berupa motif khas Maluku. Pengembangan alternatif desain motif batik dibuat tiga variasi yang bersumber dari ornamen khas Maluku dibuat prototipe produknya dan diuji ketahanan luntur warnanya. Hasil uji ketahanan luntur warna terhadap gosokan basah dari tiga prototipe produk berpredikat baik sekali terdapat pada “Motif Siwa” dan predikat baik pada motif “Siwa Talang” dan motif “Matahari Siwa Talang”.Kata kunci: desain, Maluku, motif batik, ornamenABSTRACTMaluku has much decorative ancestral cultural heritage value in the form of ornament ethnic arts and crafts skills. The result of the legacy is still sustainable living can be enjoyed as well as satisfying spiritual human consumption.Related to the sustainability of traditional values in the form of ethnic ornaments Maluku, it was developed for human needs in the form of batik cloth . The development of these ornaments will be more emphasis on the representation forms of ornamentation that is applied to a batik motif Maluku. Development of alternative design motif made three variations. The development of three alternative design motifs derived from the Maluku ornaments made and tested a prototype product color fastness. The test results of color fastness to wet rubbing of the three prototypes are excellent products predicated on the "Motif Siwa" and a good rating on the motif "Siwa Talang" and motif "Matahari Siwa

  2. Parole, Sintagmatik, dan Paradigmatik Motif Batik Mega Mendung

    Directory of Open Access Journals (Sweden)

    Rudi - Nababan

    2012-04-01

    Full Text Available ABSTRACT   Discussing traditional batik is related a lot to the organization system of fine arts element ac- companying it, either the pattern of the motif or the technique of the making. In this case, the motif of Mega Mendung Cirebon certainly has patterns and rules which are traditionally different from the other motifs in other areas. Through  semiotics analysis especially with Saussure and Pierce concept, it can be traced that batik with Cirebon motif, in this case Mega Mendung motif, has parole and langue system, as unique fine arts language in batik, and structure of visual syntagmatic and paradigmatic. In the context of batik motif as fine arts language, it is surely related to sign system as symbol and icon.       Keywords: visual semiotic, Cirebon’s batik.

  3. Treatment plan ranking using physical and biological indices

    International Nuclear Information System (INIS)

    Ebert, M. A.; University of Western Asutralia, WA

    2001-01-01

    Full text: The ranking of dose distributions is of importance in several areas such as i) comparing rival treatment plans, ii) comparing iterations in an optimisation routine, and iii) dose-assessment of clinical trial data. This study aimed to investigate the influence of choice of objective function in ranking tumour dose distributions. A series of physical (mean, maximum, minimum, standard deviation of dose) dose-volume histogram (DVH) reduction indices and biologically-based (tumour-control probability - TCP; equivalent uniform dose -EUD) indices were used to rank a series of hypothetical DVHs, as well as DVHs obtained from a series of 18 prostate patients. The distribution in ranking and change in distribution with change in indice parameters were investigated. It is found that not only is the ranking of DVHs dependent on the actual model used to perform the DVH reduction, it is also found to depend on the inherent characteristics of each model (i.e., selected parameters). The adjacent figure shows an example where the 18 prostate patients are ranked (grey-scale from black to white) by EUD when an α value of 0.8 Gy -1 is used in the model. The change of ranking as α varies is evident. Conclusion: This study has shown that the characteristics of the model selected in plan optimisation or DVH ranking will have an impact on the ranking obtained. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  4. Final report, BWR drywell debris transport Phenomena Identification and Ranking Tables (PIRTs)

    International Nuclear Information System (INIS)

    Wilson, G.E.; Boyack, B.E.; Leonard, M.T.; Williams, K.A.; Wolf, L.T.

    1997-09-01

    The Nuclear Regulatory Commission has issued a Regulatory Bulletin and accompanying Regulatory Guide (1.82, Rev. 2) which requires licensees of boiling water reactors to develop a specific plan of action (including hardware backfits, if necessary) to preclude the possibility of early emergency core cooling system strainer blockage following a postulated loss-of-coolant-accident. The postulated mechanism for strainer blockage is destruction of piping insulation in the vicinity of the break and subsequent transport of fragmented insulation to the wetwell. In the absence of more definitive information, the Regulatory Guide recommends that licensees assume a drywell debris transport fraction of 1.0. Accordingly, the Nuclear Regulatory Commission initiated research focused toward developing a technical basis to provide insights useful to regulatory oversight of licensee submittals associated with resolution of the postulated strainer blockage issue. Part of this program was directed towards experimental and analytical research leading to a more realistic specification of the debris transport through the drywell to the wetwell. To help focus this development into a cost effective effort, a panel, with broad based knowledge and experience, was formed to address the relative importance of the various phenomena that can be expected in plant response to postulated accidents that may produce strainer blockage. The resulting phenomena identification and ranking tables reported herein were used to help guide research. The phenomena occurring in boiling water reactors drywells was the specific focus of the panel, although supporting experimental data and calculations of debris transport fractions were considered

  5. Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer

    Science.gov (United States)

    Wei Poh, Zhong; Heng Gan, Chin; Lee, Eric J.; Guo, Suxian; Yip, George W.; Lam, Yulin

    2015-09-01

    Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the “sulfation code” is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.

  6. Exon silencing by UAGG motifs in response to neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Ping An

    2007-02-01

    Full Text Available Alternative pre-mRNA splicing plays fundamental roles in neurons by generating functional diversity in proteins associated with the communication and connectivity of the synapse. The CI cassette of the NMDA R1 receptor is one of a variety of exons that show an increase in exon skipping in response to cell excitation, but the molecular nature of this splicing responsiveness is not yet understood. Here we investigate the molecular basis for the induced changes in splicing of the CI cassette exon in primary rat cortical cultures in response to KCl-induced depolarization using an expression assay with a tight neuron-specific readout. In this system, exon silencing in response to neuronal excitation was mediated by multiple UAGG-type silencing motifs, and transfer of the motifs to a constitutive exon conferred a similar responsiveness by gain of function. Biochemical analysis of protein binding to UAGG motifs in extracts prepared from treated and mock-treated cortical cultures showed an increase in nuclear hnRNP A1-RNA binding activity in parallel with excitation. Evidence for the role of the NMDA receptor and calcium signaling in the induced splicing response was shown by the use of specific antagonists, as well as cell-permeable inhibitors of signaling pathways. Finally, a wider role for exon-skipping responsiveness is shown to involve additional exons with UAGG-related silencing motifs, and transcripts involved in synaptic functions. These results suggest that, at the post-transcriptional level, excitable exons such as the CI cassette may be involved in strategies by which neurons mount adaptive responses to hyperstimulation.

  7. Motif statistics and spike correlations in neuronal networks

    International Nuclear Information System (INIS)

    Hu, Yu; Shea-Brown, Eric; Trousdale, James; Josić, Krešimir

    2013-01-01

    Motifs are patterns of subgraphs of complex networks. We studied the impact of such patterns of connectivity on the level of correlated, or synchronized, spiking activity among pairs of cells in a recurrent network of integrate and fire neurons. For a range of network architectures, we find that the pairwise correlation coefficients, averaged across the network, can be closely approximated using only three statistics of network connectivity. These are the overall network connection probability and the frequencies of two second order motifs: diverging motifs, in which one cell provides input to two others, and chain motifs, in which two cells are connected via a third intermediary cell. Specifically, the prevalence of diverging and chain motifs tends to increase correlation. Our method is based on linear response theory, which enables us to express spiking statistics using linear algebra, and a resumming technique, which extrapolates from second order motifs to predict the overall effect of coupling on network correlation. Our motif-based results seek to isolate the effect of network architecture perturbatively from a known network state. (paper)

  8. Bayesian centroid estimation for motif discovery.

    Science.gov (United States)

    Carvalho, Luis

    2013-01-01

    Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  9. Bayesian centroid estimation for motif discovery.

    Directory of Open Access Journals (Sweden)

    Luis Carvalho

    Full Text Available Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  10. PageRank and rank-reversal dependence on the damping factor

    Science.gov (United States)

    Son, S.-W.; Christensen, C.; Grassberger, P.; Paczuski, M.

    2012-12-01

    PageRank (PR) is an algorithm originally developed by Google to evaluate the importance of web pages. Considering how deeply rooted Google's PR algorithm is to gathering relevant information or to the success of modern businesses, the question of rank stability and choice of the damping factor (a parameter in the algorithm) is clearly important. We investigate PR as a function of the damping factor d on a network obtained from a domain of the World Wide Web, finding that rank reversal happens frequently over a broad range of PR (and of d). We use three different correlation measures, Pearson, Spearman, and Kendall, to study rank reversal as d changes, and we show that the correlation of PR vectors drops rapidly as d changes from its frequently cited value, d0=0.85. Rank reversal is also observed by measuring the Spearman and Kendall rank correlation, which evaluate relative ranks rather than absolute PR. Rank reversal happens not only in directed networks containing rank sinks but also in a single strongly connected component, which by definition does not contain any sinks. We relate rank reversals to rank pockets and bottlenecks in the directed network structure. For the network studied, the relative rank is more stable by our measures around d=0.65 than at d=d0.

  11. PageRank and rank-reversal dependence on the damping factor.

    Science.gov (United States)

    Son, S-W; Christensen, C; Grassberger, P; Paczuski, M

    2012-12-01

    PageRank (PR) is an algorithm originally developed by Google to evaluate the importance of web pages. Considering how deeply rooted Google's PR algorithm is to gathering relevant information or to the success of modern businesses, the question of rank stability and choice of the damping factor (a parameter in the algorithm) is clearly important. We investigate PR as a function of the damping factor d on a network obtained from a domain of the World Wide Web, finding that rank reversal happens frequently over a broad range of PR (and of d). We use three different correlation measures, Pearson, Spearman, and Kendall, to study rank reversal as d changes, and we show that the correlation of PR vectors drops rapidly as d changes from its frequently cited value, d_{0}=0.85. Rank reversal is also observed by measuring the Spearman and Kendall rank correlation, which evaluate relative ranks rather than absolute PR. Rank reversal happens not only in directed networks containing rank sinks but also in a single strongly connected component, which by definition does not contain any sinks. We relate rank reversals to rank pockets and bottlenecks in the directed network structure. For the network studied, the relative rank is more stable by our measures around d=0.65 than at d=d_{0}.

  12. Global network centrality of university rankings

    Science.gov (United States)

    Guo, Weisi; Del Vecchio, Marco; Pogrebna, Ganna

    2017-10-01

    Universities and higher education institutions form an integral part of the national infrastructure and prestige. As academic research benefits increasingly from international exchange and cooperation, many universities have increased investment in improving and enabling their global connectivity. Yet, the relationship of university performance and its global physical connectedness has not been explored in detail. We conduct, to our knowledge, the first large-scale data-driven analysis into whether there is a correlation between university relative ranking performance and its global connectivity via the air transport network. The results show that local access to global hubs (as measured by air transport network betweenness) strongly and positively correlates with the ranking growth (statistical significance in different models ranges between 5% and 1% level). We also found that the local airport's aggregate flight paths (degree) and capacity (weighted degree) has no effect on university ranking, further showing that global connectivity distance is more important than the capacity of flight connections. We also examined the effect of local city economic development as a confounding variable and no effect was observed suggesting that access to global transportation hubs outweighs economic performance as a determinant of university ranking. The impact of this research is that we have determined the importance of the centrality of global connectivity and, hence, established initial evidence for further exploring potential connections between university ranking and regional investment policies on improving global connectivity.

  13. Ranking structures and rank-rank correlations of countries: The FIFA and UEFA cases

    Science.gov (United States)

    Ausloos, Marcel; Cloots, Rudi; Gadomski, Adam; Vitanov, Nikolay K.

    2014-04-01

    Ranking of agents competing with each other in complex systems may lead to paradoxes according to the pre-chosen different measures. A discussion is presented on such rank-rank, similar or not, correlations based on the case of European countries ranked by UEFA and FIFA from different soccer competitions. The first question to be answered is whether an empirical and simple law is obtained for such (self-) organizations of complex sociological systems with such different measuring schemes. It is found that the power law form is not the best description contrary to many modern expectations. The stretched exponential is much more adequate. Moreover, it is found that the measuring rules lead to some inner structures in both cases.

  14. AMP-acetyl CoA synthetase from Leishmania donovani: identification and functional analysis of 'PX4GK' motif.

    Science.gov (United States)

    Soumya, Neelagiri; Kumar, I Sravan; Shivaprasad, S; Gorakh, Landage Nitin; Dinesh, Neeradi; Swamy, Kayala Kambagiri; Singh, Sushma

    2015-04-01

    An adenosine monophosphate forming acetyl CoA synthetase (AceCS) which is the key enzyme involved in the conversion of acetate to acetyl CoA has been identified from Leishmania donovani for the first time. Sequence analysis of L. donovani AceCS (LdAceCS) revealed the presence of a 'PX4GK' motif which is highly conserved throughout organisms with higher sequence identity (96%) to lower sequence identity (38%). A ∼ 77 kDa heterologous protein with C-terminal 6X His-tag was expressed in Escherichia coli. Expression of LdAceCS in promastigotes was confirmed by western blot and RT-PCR analysis. Immunolocalization studies revealed that it is a cytosolic protein. We also report the kinetic characterization of recombinant LdAceCS with acetate, adenosine 5'-triphosphate, coenzyme A and propionate as substrates. Site directed mutagenesis of residues in conserved PX4GK motif of LdAceCS was performed to gain insight into its potential role in substrate binding, catalysis and its role in maintaining structural integrity of the protein. P646A, G651A and K652R exhibited more than 90% loss in activity signifying its indispensible role in the enzyme activity. Substitution of other residues in this motif resulted in altered substrate specificity and catalysis. However, none of them had any role in modulation of the secondary structure of the protein except G651A mutant. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Cave acoustics in prehistory: Exploring the association of Palaeolithic visual motifs and acoustic response.

    Science.gov (United States)

    Fazenda, Bruno; Scarre, Chris; Till, Rupert; Pasalodos, Raquel Jiménez; Guerra, Manuel Rojo; Tejedor, Cristina; Peredo, Roberto Ontañón; Watson, Aaron; Wyatt, Simon; Benito, Carlos García; Drinkall, Helen; Foulds, Frederick

    2017-09-01

    During the 1980 s, acoustic studies of Upper Palaeolithic imagery in French caves-using the technology then available-suggested a relationship between acoustic response and the location of visual motifs. This paper presents an investigation, using modern acoustic measurement techniques, into such relationships within the caves of La Garma, Las Chimeneas, La Pasiega, El Castillo, and Tito Bustillo in Northern Spain. It addresses methodological issues concerning acoustic measurement at enclosed archaeological sites and outlines a general framework for extraction of acoustic features that may be used to support archaeological hypotheses. The analysis explores possible associations between the position of visual motifs (which may be up to 40 000 yrs old) and localized acoustic responses. Results suggest that motifs, in general, and lines and dots, in particular, are statistically more likely to be found in places where reverberation is moderate and where the low frequency acoustic response has evidence of resonant behavior. The work presented suggests that an association of the location of Palaeolithic motifs with acoustic features is a statistically weak but tenable hypothesis, and that an appreciation of sound could have influenced behavior among Palaeolithic societies of this region.

  16. CONTEMPORARY USAGE OF TRADITIONAL TURKISH MOTIFS IN PRODUCT DESIGNS

    Directory of Open Access Journals (Sweden)

    Tulay Gumuser

    2012-12-01

    Full Text Available The aim of this study is to identify the traditional Turkish motifs and its relations among present industrial designs. Traditional Turkish motifs played a very important role in 16th century onwards. The arts of the Ottoman Empire were used because of their symbolic meanings and unique styles. When we examine these motifs we encounter; Tiger Stripe, Three Spot (Çintemani, Rumi, Hatayi, Penç, Cloud, Crescent, Star, Crown, Hyacinth, Tulip and Carnation motifs. Nowadays, Turkish designers have begun to use these traditional Turkish motifs in their designs so as to create differences and awareness in the world design. The examples of these industrial designs, using the Turkish motifs, have survived and have Ottoman heritage and historical value. In this study, the Turkish motifs will be examined along with their focus on contemporary Turkish industrial designs used today.

  17. RNA motif search with data-driven element ordering.

    Science.gov (United States)

    Rampášek, Ladislav; Jimenez, Randi M; Lupták, Andrej; Vinař, Tomáš; Brejová, Broňa

    2016-05-18

    In this paper, we study the problem of RNA motif search in long genomic sequences. This approach uses a combination of sequence and structure constraints to uncover new distant homologs of known functional RNAs. The problem is NP-hard and is traditionally solved by backtracking algorithms. We have designed a new algorithm for RNA motif search and implemented a new motif search tool RNArobo. The tool enhances the RNAbob descriptor language, allowing insertions in helices, which enables better characterization of ribozymes and aptamers. A typical RNA motif consists of multiple elements and the running time of the algorithm is highly dependent on their ordering. By approaching the element ordering problem in a principled way, we demonstrate more than 100-fold speedup of the search for complex motifs compared to previously published tools. We have developed a new method for RNA motif search that allows for a significant speedup of the search of complex motifs that include pseudoknots. Such speed improvements are crucial at a time when the rate of DNA sequencing outpaces growth in computing. RNArobo is available at http://compbio.fmph.uniba.sk/rnarobo .

  18. Touch DNA collection versus firearm fingerprinting: comparing evidence production and identification outcomes.

    Science.gov (United States)

    Nunn, Samuel

    2013-05-01

    A project by a metropolitan police agency in 2008-2009 had police use touch DNA kits to collect cell samples from seized firearms. To assess outcomes, results of touch DNA swabbing of firearms were compared to fingerprinting firearm evidence. The rationale was that fingerprinting, as the older technology, was the baseline against which to compare touch DNA. But little is known about ways to measure touch DNA productivity compared to fingerprinting. To examine differences between the two requires comparable measurements. Two measures were used: quantity of probative or investigative evidence produced and identification outcomes. When applied to firearms seized within an Indianapolis, IN police district, touch DNA produced a larger volume of evidence than fingerprinting, but identification outcomes for the two methods were equal. Because touch DNA was deployed by police patrol officers, there are implications for firearm forensics and the choice of forensic approaches used by police. © 2013 American Academy of Forensic Sciences.

  19. Identification of volatile and semivolatile compounds in chemical ionization GC-MS using a mass-to-structure (MTS) Search Engine with integral isotope pattern ranking.

    Science.gov (United States)

    Liao, Wenta; Draper, William M

    2013-02-21

    The mass-to-structure or MTS Search Engine is an Access 2010 database containing theoretical molecular mass information for 19,438 compounds assembled from common sources such as the Merck Index, pesticide and pharmaceutical compilations, and chemical catalogues. This database, which contains no experimental mass spectral data, was developed as an aid to identification of compounds in atmospheric pressure ionization (API)-LC-MS. This paper describes a powerful upgrade to this database, a fully integrated utility for filtering or ranking candidates based on isotope ratios and patterns. The new MTS Search Engine is applied here to the identification of volatile and semivolatile compounds including pesticides, nitrosoamines and other pollutants. Methane and isobutane chemical ionization (CI) GC-MS spectra were obtained from unit mass resolution mass spectrometers to determine MH(+) masses and isotope ratios. Isotopes were measured accurately with errors of Search Engine and details performance testing with over 50 model compounds.

  20. Rank one chaos in a class of planar systems with heteroclinic cycle.

    Science.gov (United States)

    Chen, Fengjuan; Han, Maoan

    2009-12-01

    In this paper, we study rank one chaos in a class of planar systems with heteroclinic cycle. We first find a stable limit cycle inside the heteroclinic cycle. We then add an external periodic forcing to create rank one chaos. We follow a step-by-step procedure guided by the theory of rank one chaos to find experimental evidence of strange attractors with Sinai, Ruelle, and Bowen measures.

  1. Analisis Unsur Matematika pada Motif Sulam Usus

    Directory of Open Access Journals (Sweden)

    Fredi Ganda Putra

    2017-12-01

    Full Text Available Based on interviews with researchers sources said that the beginning of the intestine embroidery is an art of genuine crafts. Called the intestine embroidery because this technique is a technique of combining a strand of cloth resembling the intestine formed according to the pattern by means of embroidered using a thread. Intestinal embroidery techniques were originally used to create a cover of the women's customary wardrobe of Lampung or often referred to as bebe. But not many people in Lampung, especially people who live in Lampung are still many who do not know and recognize the intestine embroidery because most only know tapis only characteristic of Lampung, besides that there are other cultural results that is embroidered intestine. There are still many who do not know that the intestine motif there is a knowledge of mathematics. The researcher's problem formulation is whether there are mathematical elements contained in the intestine embroidery motif based on the concept of geometry. The purpose of this study is to determine whether there are elements of mathematics contained in the intestine motif based on the concept of geometry. Subjects in this study consisted of 4 people obtained by purposive sampling technique. From the results of data analysis conducted by using descriptive analysis and discussion as follows: (1 Intestinal embroidery motif contains the meaning of mathematics and culture or often called Etnomatematika. On the meaning of culture there is a link between the embroidery intestine with a culture that has been there before as the existence of cultural linkage between Hindu belief Buddhism and there are similarities of motifs and decorative patterns contained in the motif embroidery intestine with ornamental variety in Indonesia. (2 The relationship between the intestine with mathematical motifs there are elements of mathematics such as geometry elements in the form of geometry of dimension one and dimension two, and the

  2. SibRank: Signed bipartite network analysis for neighbor-based collaborative ranking

    Science.gov (United States)

    Shams, Bita; Haratizadeh, Saman

    2016-09-01

    Collaborative ranking is an emerging field of recommender systems that utilizes users' preference data rather than rating values. Unfortunately, neighbor-based collaborative ranking has gained little attention despite its more flexibility and justifiability. This paper proposes a novel framework, called SibRank that seeks to improve the state of the art neighbor-based collaborative ranking methods. SibRank represents users' preferences as a signed bipartite network, and finds similar users, through a novel personalized ranking algorithm in signed networks.

  3. Motif signatures of transcribed enhancers

    KAUST Repository

    Kleftogiannis, Dimitrios

    2017-09-14

    In mammalian cells, transcribed enhancers (TrEn) play important roles in the initiation of gene expression and maintenance of gene expression levels in spatiotemporal manner. One of the most challenging questions in biology today is how the genomic characteristics of enhancers relate to enhancer activities. This is particularly critical, as several recent studies have linked enhancer sequence motifs to specific functional roles. To date, only a limited number of enhancer sequence characteristics have been investigated, leaving space for exploring the enhancers genomic code in a more systematic way. To address this problem, we developed a novel computational method, TELS, aimed at identifying predictive cell type/tissue specific motif signatures. We used TELS to compile a comprehensive catalog of motif signatures for all known TrEn identified by the FANTOM5 consortium across 112 human primary cells and tissues. Our results confirm that distinct cell type/tissue specific motif signatures characterize TrEn. These signatures allow discriminating successfully a) TrEn from random controls, proxy of non-enhancer activity, and b) cell type/tissue specific TrEn from enhancers expressed and transcribed in different cell types/tissues. TELS codes and datasets are publicly available at http://www.cbrc.kaust.edu.sa/TELS.

  4. A novel fibronectin binding motif in MSCRAMMs targets F3 modules.

    Directory of Open Access Journals (Sweden)

    Sabitha Prabhakaran

    Full Text Available BBK32 is a surface expressed lipoprotein and fibronectin (Fn-binding microbial surface component recognizing adhesive matrix molecule (MSCRAMM of Borrelia burgdorferi, the causative agent of Lyme disease. Previous studies from our group showed that BBK32 is a virulence factor in experimental Lyme disease and located the Fn-binding region to residues 21-205 of the lipoprotein.Studies aimed at identifying interacting sites between BBK32 and Fn revealed an interaction between the MSCRAMM and the Fn F3 modules. Further analysis of this interaction showed that BBK32 can cause the aggregation of human plasma Fn in a similar concentration-dependent manner to that of anastellin, the superfibronectin (sFn inducing agent. The resulting Fn aggregates are conformationally distinct from plasma Fn as indicated by a change in available thermolysin cleavage sites. Recombinant BBK32 and anastellin affect the structure of Fn matrices formed by cultured fibroblasts and inhibit endothelial cell proliferation similarly. Within BBK32, we have located the sFn-forming activity to a region between residues 160 and 175 which contains two sequence motifs that are also found in anastellin. Synthetic peptides mimicking these motifs induce Fn aggregation, whereas a peptide with a scrambled sequence motif was inactive, suggesting that these motifs represent the sFn-inducing sequence.We conclude that BBK32 induces the formation of Fn aggregates that are indistinguishable from those formed by anastellin. The results of this study provide evidence for how bacteria can target host proteins to manipulate host cell activities.

  5. Kinematic evidence of satellite galaxy populations in the potential wells of first-ranked cluster galaxies

    Science.gov (United States)

    Cowie, L. L.; Hu, E. M.

    1986-01-01

    The velocities of 38 centrally positioned galaxies (r much less than 100 kpc) were measured relative to the velocity of the first-ranked galaxy in 14 rich clusters. Analysis of the velocity distribution function of this sample and of previous data shows that the population cannot be fit by a single Gaussian. An adequate fit is obtained if 60 percent of the objects lie in a Gaussian with sigma = 250 km/s and the remainder in a population with sigma = 1400 km/s. All previous data sets are individually consistent with this conclusion. This suggests that there is a bound population of galaxies in the potential well of the central galaxy in addition to the normal population of the cluster core. This is taken as supporting evidence for the galactic cannibalism model of cD galaxy formation.

  6. Ranking nodes in growing networks: When PageRank fails.

    Science.gov (United States)

    Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng

    2015-11-10

    PageRank is arguably the most popular ranking algorithm which is being applied in real systems ranging from information to biological and infrastructure networks. Despite its outstanding popularity and broad use in different areas of science, the relation between the algorithm's efficacy and properties of the network on which it acts has not yet been fully understood. We study here PageRank's performance on a network model supported by real data, and show that realistic temporal effects make PageRank fail in individuating the most valuable nodes for a broad range of model parameters. Results on real data are in qualitative agreement with our model-based findings. This failure of PageRank reveals that the static approach to information filtering is inappropriate for a broad class of growing systems, and suggest that time-dependent algorithms that are based on the temporal linking patterns of these systems are needed to better rank the nodes.

  7. Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs

    Directory of Open Access Journals (Sweden)

    Jockusch Rebecca A

    2006-11-01

    Full Text Available Abstract Background By screening a plasmid library for proteins that could cause silencing when targeted to the HMR locus in Saccharomyces cerevisiae, we previously reported the identification of Rtt107/Esc4 based on its ability to establish silent chromatin. In this study we aimed to determine the mechanism of Rtt107/Esc4 targeted silencing and also learn more about its biological functions. Results Targeted silencing by Rtt107/Esc4 was dependent on the SIR genes, which encode obligatory structural and enzymatic components of yeast silent chromatin. Based on its sequence, Rtt107/Esc4 was predicted to contain six BRCT motifs. This motif, originally identified in the human breast tumor suppressor gene BRCA1, is a protein interaction domain. The targeted silencing activity of Rtt107/Esc4 resided within the C-terminal two BRCT motifs, and this region of the protein bound to Sir3 in two-hybrid tests. Deletion of RTT107/ESC4 caused sensitivity to the DNA damaging agent MMS as well as to hydroxyurea. A two-hybrid screen showed that the N-terminal BRCT motifs of Rtt107/Esc4 bound to Slx4, a protein previously shown to be involved in DNA repair and required for viability in a strain lacking the DNA helicase Sgs1. Like SLX genes, RTT107ESC4 interacted genetically with SGS1; esc4Δ sgs1Δ mutants were viable, but exhibited a slow-growth phenotype and also a synergistic DNA repair defect. Conclusion Rtt107/Esc4 binds to the silencing protein Sir3 and the DNA repair protein Slx4 via different BRCT motifs, thus providing a bridge linking silent chromatin to DNA repair enzymes.

  8. The Monitoring and Affinity Purification of Proteins Using Dual Tags with Tetracysteine Motifs

    Science.gov (United States)

    Giannone, Richard J.; Liu, Yie; Wang, Yisong

    Identification and characterization of protein-protein interaction networks is essential for the elucidation of biochemical mechanisms and cellular function. Affinity purification in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a very powerful tactic for the identification of specific protein-protein interactions. In this chapter, we describe a comprehensive methodology that uses our recently developed dual-tag affinity purification system for the enrichment and identification of mammalian protein complexes. The protocol covers a series of separate but sequentially related techniques focused on the facile monitoring and purification of a dual-tagged protein of interest and its interacting partners via a system built with tetracysteine motifs and various combinations of affinity tags. Using human telomeric repeat binding factor 2 (TRF2) as an example, we demonstrate the power of the system in terms of bait protein recovery after dual-tag affinity purification, detection of bait protein subcellular localization and expression, and successful identification of known and potentially novel TRF2 interacting proteins. Although the protocol described here has been optimized for the identification and characterization of TRF2-associated proteins, it is, in principle, applicable to the study of any other mammalian protein complexes that may be of interest to the research community.

  9. Reduced Rank Regression

    DEFF Research Database (Denmark)

    Johansen, Søren

    2008-01-01

    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...

  10. RankProdIt: A web-interactive Rank Products analysis tool

    Directory of Open Access Journals (Sweden)

    Laing Emma

    2010-08-01

    Full Text Available Abstract Background The first objective of a DNA microarray experiment is typically to generate a list of genes or probes that are found to be differentially expressed or represented (in the case of comparative genomic hybridizations and/or copy number variation between two conditions or strains. Rank Products analysis comprises a robust algorithm for deriving such lists from microarray experiments that comprise small numbers of replicates, for example, less than the number required for the commonly used t-test. Currently, users wishing to apply Rank Products analysis to their own microarray data sets have been restricted to the use of command line-based software which can limit its usage within the biological community. Findings Here we have developed a web interface to existing Rank Products analysis tools allowing users to quickly process their data in an intuitive and step-wise manner to obtain the respective Rank Product or Rank Sum, probability of false prediction and p-values in a downloadable file. Conclusions The online interactive Rank Products analysis tool RankProdIt, for analysis of any data set containing measurements for multiple replicated conditions, is available at: http://strep-microarray.sbs.surrey.ac.uk/RankProducts

  11. RankExplorer: Visualization of Ranking Changes in Large Time Series Data.

    Science.gov (United States)

    Shi, Conglei; Cui, Weiwei; Liu, Shixia; Xu, Panpan; Chen, Wei; Qu, Huamin

    2012-12-01

    For many applications involving time series data, people are often interested in the changes of item values over time as well as their ranking changes. For example, people search many words via search engines like Google and Bing every day. Analysts are interested in both the absolute searching number for each word as well as their relative rankings. Both sets of statistics may change over time. For very large time series data with thousands of items, how to visually present ranking changes is an interesting challenge. In this paper, we propose RankExplorer, a novel visualization method based on ThemeRiver to reveal the ranking changes. Our method consists of four major components: 1) a segmentation method which partitions a large set of time series curves into a manageable number of ranking categories; 2) an extended ThemeRiver view with embedded color bars and changing glyphs to show the evolution of aggregation values related to each ranking category over time as well as the content changes in each ranking category; 3) a trend curve to show the degree of ranking changes over time; 4) rich user interactions to support interactive exploration of ranking changes. We have applied our method to some real time series data and the case studies demonstrate that our method can reveal the underlying patterns related to ranking changes which might otherwise be obscured in traditional visualizations.

  12. Efficient motif finding algorithms for large-alphabet inputs

    Directory of Open Access Journals (Sweden)

    Pavlovic Vladimir

    2010-10-01

    Full Text Available Abstract Background We consider the problem of identifying motifs, recurring or conserved patterns, in the biological sequence data sets. To solve this task, we present a new deterministic algorithm for finding patterns that are embedded as exact or inexact instances in all or most of the input strings. Results The proposed algorithm (1 improves search efficiency compared to existing algorithms, and (2 scales well with the size of alphabet. On a synthetic planted DNA motif finding problem our algorithm is over 10× more efficient than MITRA, PMSPrune, and RISOTTO for long motifs. Improvements are orders of magnitude higher in the same setting with large alphabets. On benchmark TF-binding site problems (FNP, CRP, LexA we observed reduction in running time of over 12×, with high detection accuracy. The algorithm was also successful in rapidly identifying protein motifs in Lipocalin, Zinc metallopeptidase, and supersecondary structure motifs for Cadherin and Immunoglobin families. Conclusions Our algorithm reduces computational complexity of the current motif finding algorithms and demonstrate strong running time improvements over existing exact algorithms, especially in important and difficult cases of large-alphabet sequences.

  13. Identification of Protein Complexes Using Weighted PageRank-Nibble Algorithm and Core-Attachment Structure.

    Science.gov (United States)

    Peng, Wei; Wang, Jianxin; Zhao, Bihai; Wang, Lusheng

    2015-01-01

    Protein complexes play a significant role in understanding the underlying mechanism of most cellular functions. Recently, many researchers have explored computational methods to identify protein complexes from protein-protein interaction (PPI) networks. One group of researchers focus on detecting local dense subgraphs which correspond to protein complexes by considering local neighbors. The drawback of this kind of approach is that the global information of the networks is ignored. Some methods such as Markov Clustering algorithm (MCL), PageRank-Nibble are proposed to find protein complexes based on random walk technique which can exploit the global structure of networks. However, these methods ignore the inherent core-attachment structure of protein complexes and treat adjacent node equally. In this paper, we design a weighted PageRank-Nibble algorithm which assigns each adjacent node with different probability, and propose a novel method named WPNCA to detect protein complex from PPI networks by using weighted PageRank-Nibble algorithm and core-attachment structure. Firstly, WPNCA partitions the PPI networks into multiple dense clusters by using weighted PageRank-Nibble algorithm. Then the cores of these clusters are detected and the rest of proteins in the clusters will be selected as attachments to form the final predicted protein complexes. The experiments on yeast data show that WPNCA outperforms the existing methods in terms of both accuracy and p-value. The software for WPNCA is available at "http://netlab.csu.edu.cn/bioinfomatics/weipeng/WPNCA/download.html".

  14. Rank Advancement in Academic Careers: Sex Differences and the Effects of Productivity.

    Science.gov (United States)

    Long, J. Scott; And Others

    1993-01-01

    Presents evidence on sex differences in rank advancement in academic careers, and considers the relative importance of quality and quantity of publications. Results for 556 male and 450 female biochemists show the importance of time in rank and number of publications and that rates of promotion are lower for women. (SLD)

  15. Person-Environment Mergence and Separation: Otto Rank's Psychology of Emotion, Personality, and Culture.

    Science.gov (United States)

    Sullivan, Daniel

    2016-12-01

    Between 1924 and 1939 Otto Rank put forward three major elements of a comprehensive theoretical edifice that has yet to be fully articulated. These are conceptually linked by the fundamental importance of person-environment mergence and separation. Rank's theory of emotions highlights anxiety as the affect of separation, and guilt as the feeling that binds the individual to others. His personality theory distinguishes between the partialist, who responds to life fear with identification, and the totalist, who responds to death fear with projection. His cultural psychology contrasts primal collectivism with contemporary individualism, which orients the person toward individual immortality striving. Individualism has produced problematic self-consciousness and neuroticism, in the face of which Rank struggled to find a new psychology.

  16. Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif

    OpenAIRE

    Shchedrina, Valentina A.; Novoselov, Sergey V.; Malinouski, Mikalai Yu.; Gladyshev, Vadim N.

    2007-01-01

    Selenocysteine (Sec, U) insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element. Selenoproteins with known functions are oxidoreductases containing a single redox-active Sec in their active sites. In this work, we identified a family of selenoproteins, designated SelL, containing two Sec separated by two other residues to form a UxxU motif. SelL proteins show an unusual occur...

  17. PageRank as a method to rank biomedical literature by importance.

    Science.gov (United States)

    Yates, Elliot J; Dixon, Louise C

    2015-01-01

    Optimal ranking of literature importance is vital in overcoming article overload. Existing ranking methods are typically based on raw citation counts, giving a sum of 'inbound' links with no consideration of citation importance. PageRank, an algorithm originally developed for ranking webpages at the search engine, Google, could potentially be adapted to bibliometrics to quantify the relative importance weightings of a citation network. This article seeks to validate such an approach on the freely available, PubMed Central open access subset (PMC-OAS) of biomedical literature. On-demand cloud computing infrastructure was used to extract a citation network from over 600,000 full-text PMC-OAS articles. PageRanks and citation counts were calculated for each node in this network. PageRank is highly correlated with citation count (R = 0.905, P PageRank can be trivially computed on commodity cluster hardware and is linearly correlated with citation count. Given its putative benefits in quantifying relative importance, we suggest it may enrich the citation network, thereby overcoming the existing inadequacy of citation counts alone. We thus suggest PageRank as a feasible supplement to, or replacement of, existing bibliometric ranking methods.

  18. Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation.

    Science.gov (United States)

    Michael, Sushama; Travé, Gilles; Ramu, Chenna; Chica, Claudia; Gibson, Toby J

    2008-02-15

    KEN-box-mediated target selection is one of the mechanisms used in the proteasomal destruction of mitotic cell cycle proteins via the APC/C complex. While annotating the Eukaryotic Linear Motif resource (ELM, http://elm.eu.org/), we found that KEN motifs were significantly enriched in human protein entries with cell cycle keywords in the UniProt/Swiss-Prot database-implying that KEN-boxes might be more common than reported. Matches to short linear motifs in protein database searches are not, per se, significant. KEN-box enrichment with cell cycle Gene Ontology terms suggests that collectively these motifs are functional but does not prove that any given instance is so. Candidates were surveyed for native disorder prediction using GlobPlot and IUPred and for motif conservation in homologues. Among >25 strong new candidates, the most notable are human HIPK2, CHFR, CDC27, Dab2, Upf2, kinesin Eg5, DNA Topoisomerase 1 and yeast Cdc5 and Swi5. A similar number of weaker candidates were present. These proteins have yet to be tested for APC/C targeted destruction, providing potential new avenues of research.

  19. Biometric identification using knee X-rays.

    Science.gov (United States)

    Shamir, Lior; Ling, Shari; Rahimi, Salim; Ferrucci, Luigi; Goldberg, Ilya G

    2009-01-01

    Identification of people often makes use of unique features of the face, fingerprints and retina. Beyond this, a similar identifying process can be applied to internal parts of the body that are not visible to the unaided eye. Here we show that knee X-rays can be used for the identification of individual persons. The image analysis method is based on the wnd-charm algorithm, which has been found effective for the diagnosis of clinical conditions of knee joints. Experimental results show that the rank-10 identification accuracy using a dataset of 425 individuals is ~56%, and the rank-1 accuracy is ~34%. The dataset contained knee X-rays taken several years apart from each other, showing that the identifiable features correspond to specific persons, rather than the present clinical condition of the joint.

  20. Development of a preliminary PIRT (Phenomena Identification and Ranking Table) of thermal-hydraulic phenomena for 330MWt SMART integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Chung, B. D.; Lee, W. J.; Sim, S. K.; Song, J. H.; Kim, H. C.

    1997-09-01

    The work reported in this document identifies the thermal-hydraulic phenomena that are expected to occur during a number of key transients in a 330 MWt SMART integral reactor which is under development at KAERI. The result of this efforts is based on the current design concept of SMART integral reactor. Although the design is still evolving, the preliminary Phenomena Identification and Ranking Table (PIRT) has been developed based on the experts` knowledge and experience. The preliminary PIRT has been developed by the consensus of KAERI expert panelists and AHP (Analytical Hierarchy Process). Preliminary PIRT developed in this report is intended for use to identify and integrate development areas of further experimental tests needed and thermal-hydraulic models and correlations and code improvements for the safety analysis of the SMART integral reactor. (author). 7 refs., 21 tabs., 22 figs.

  1. Hazard identification of contaminated sites. Ranking potential toxicity of organic sediment extracts in crustacean and fish

    Energy Technology Data Exchange (ETDEWEB)

    Karlsson, J.; Sundberg, H.; Aakerman, G.; Grunder, K.; Eklund, B.; Breitholtz, M. [Dept. of Applied Environmental Science (ITM), Stockholm Univ. (Sweden)

    2008-09-15

    Background, aim, and scope: It is well known that contaminated sediments represent a potential long-term source of pollutants to the aquatic environment. To protect human and ecosystem health, it is becoming common to remediate contaminated sites. However, the great cost associated with, e.g., dredging in combination with the large numbers of contaminated sites makes it crucial to pinpoint those sites that are in greatest need of remediation. In most European countries, this prioritization process has almost exclusively been based on chemical analyses of known substances; only seldom toxicity data has been considered. The main objective of the current study was therefore to develop a tool for hazard identification of sediment by ranking potential toxicity of organic sediment extracts in a crustacean and a fish. A secondary objective was to investigate the difference in potential toxicity between compounds with different polarities. Materials and methods Early life stages of the crustacean Nitocra spinipes and the fish Oncorhynchus mykiss, which represent organisms from different trophic levels (primary and secondary consumer) and with different routes of exposure (i.e. ingestion through food, diffusive uptake, and maternal transfer), were exposed to hexane and acetone fractions (semi-polar compounds) of sediment from five locations, ranging from heavily to low contaminated. Preliminary tests showed that the extracts were non-bioavailable to the crustacean when exposed via water, and the extracts were therefore loaded on silica gel. Rainbow trout embryos were exposed using nano-injection technique. Results and discussion Clear concentration-response relationships of both mortality and larval development were observed in all tests with N. spinipes. Also for rainbow trout, the observed effects (e.g., abnormality, hemorrhage, asymmetric yolk sac) followed a dose-related pattern. Interestingly, our results indicate that some of the locations contained toxic semi

  2. The Q Motif Is Involved in DNA Binding but Not ATP Binding in ChlR1 Helicase.

    Directory of Open Access Journals (Sweden)

    Hao Ding

    Full Text Available Helicases are molecular motors that couple the energy of ATP hydrolysis to the unwinding of structured DNA or RNA and chromatin remodeling. The conversion of energy derived from ATP hydrolysis into unwinding and remodeling is coordinated by seven sequence motifs (I, Ia, II, III, IV, V, and VI. The Q motif, consisting of nine amino acids (GFXXPXPIQ with an invariant glutamine (Q residue, has been identified in some, but not all helicases. Compared to the seven well-recognized conserved helicase motifs, the role of the Q motif is less acknowledged. Mutations in the human ChlR1 (DDX11 gene are associated with a unique genetic disorder known as Warsaw Breakage Syndrome, which is characterized by cellular defects in genome maintenance. To examine the roles of the Q motif in ChlR1 helicase, we performed site directed mutagenesis of glutamine to alanine at residue 23 in the Q motif of ChlR1. ChlR1 recombinant protein was overexpressed and purified from HEK293T cells. ChlR1-Q23A mutant abolished the helicase activity of ChlR1 and displayed reduced DNA binding ability. The mutant showed impaired ATPase activity but normal ATP binding. A thermal shift assay revealed that ChlR1-Q23A has a melting point value similar to ChlR1-WT. Partial proteolysis mapping demonstrated that ChlR1-WT and Q23A have a similar globular structure, although some subtle conformational differences in these two proteins are evident. Finally, we found ChlR1 exists and functions as a monomer in solution, which is different from FANCJ, in which the Q motif is involved in protein dimerization. Taken together, our results suggest that the Q motif is involved in DNA binding but not ATP binding in ChlR1 helicase.

  3. μXRF analysis of decoration motifs on Majolica pottery

    International Nuclear Information System (INIS)

    Padilla Lavarez, Roman; Van Espen, Pierr M.; Janssens, K; Schalm, O.

    2001-01-01

    μXRF analysis of decoration motifs on Majolica pottery in fragments corresponding to several Majolica types was carried out using an spectrometer comprising a low power Mo X-ray tube and a elliptic-shape concentration lens with a 60 um spot. Both surface scanning and spot measurements were carried a out, allowing the qualitative identification of the inorganic pigments used for the surface painting decoration and the quantitative analysis of the main glaze composition. The absence of interference signal arising from the excitation on the underlying paste when analysing thin-lead glazing was evaluated, allowing ensuring the suitable of the analytical procedures. A distinction was found between different types of majolica by the composition of the lead tin glaze enamel and by the presence of other elements in the blue, black and orange decoration

  4. DNA motif alignment by evolving a population of Markov chains.

    Science.gov (United States)

    Bi, Chengpeng

    2009-01-30

    Deciphering cis-regulatory elements or de novo motif-finding in genomes still remains elusive although much algorithmic effort has been expended. The Markov chain Monte Carlo (MCMC) method such as Gibbs motif samplers has been widely employed to solve the de novo motif-finding problem through sequence local alignment. Nonetheless, the MCMC-based motif samplers still suffer from local maxima like EM. Therefore, as a prerequisite for finding good local alignments, these motif algorithms are often independently run a multitude of times, but without information exchange between different chains. Hence it would be worth a new algorithm design enabling such information exchange. This paper presents a novel motif-finding algorithm by evolving a population of Markov chains with information exchange (PMC), each of which is initialized as a random alignment and run by the Metropolis-Hastings sampler (MHS). It is progressively updated through a series of local alignments stochastically sampled. Explicitly, the PMC motif algorithm performs stochastic sampling as specified by a population-based proposal distribution rather than individual ones, and adaptively evolves the population as a whole towards a global maximum. The alignment information exchange is accomplished by taking advantage of the pooled motif site distributions. A distinct method for running multiple independent Markov chains (IMC) without information exchange, or dubbed as the IMC motif algorithm, is also devised to compare with its PMC counterpart. Experimental studies demonstrate that the performance could be improved if pooled information were used to run a population of motif samplers. The new PMC algorithm was able to improve the convergence and outperformed other popular algorithms tested using simulated and biological motif sequences.

  5. A Time-Space Domain Information Fusion Method for Specific Emitter Identification Based on Dempster-Shafer Evidence Theory.

    Science.gov (United States)

    Jiang, Wen; Cao, Ying; Yang, Lin; He, Zichang

    2017-08-28

    Specific emitter identification plays an important role in contemporary military affairs. However, most of the existing specific emitter identification methods haven't taken into account the processing of uncertain information. Therefore, this paper proposes a time-space domain information fusion method based on Dempster-Shafer evidence theory, which has the ability to deal with uncertain information in the process of specific emitter identification. In this paper, radars will generate a group of evidence respectively based on the information they obtained, and our main task is to fuse the multiple groups of evidence to get a reasonable result. Within the framework of recursive centralized fusion model, the proposed method incorporates a correlation coefficient, which measures the relevance between evidence and a quantum mechanical approach, which is based on the parameters of radar itself. The simulation results of an illustrative example demonstrate that the proposed method can effectively deal with uncertain information and get a reasonable recognition result.

  6. Quantile driven identification of structural derivatives

    OpenAIRE

    Andrew Chesher

    2001-01-01

    Conditions are derived under which there is local nonparametric identification of derivatives of structural equations in nonlinear triangular simultaneous equations systems. The attack on this problem is via conditional quantile functions and exploits local quantile independence conditions. The identification conditions include local analogues of the order and rank conditions familiar in the analysis of linear simultaneous equations models. The objects whose identification is sought are deriv...

  7. RANK and RANK ligand expression in primary human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Daniel Branstetter

    2015-09-01

    Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79 of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.

  8. Ranking nodes in growing networks: When PageRank fails

    Science.gov (United States)

    Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng

    2015-11-01

    PageRank is arguably the most popular ranking algorithm which is being applied in real systems ranging from information to biological and infrastructure networks. Despite its outstanding popularity and broad use in different areas of science, the relation between the algorithm’s efficacy and properties of the network on which it acts has not yet been fully understood. We study here PageRank’s performance on a network model supported by real data, and show that realistic temporal effects make PageRank fail in individuating the most valuable nodes for a broad range of model parameters. Results on real data are in qualitative agreement with our model-based findings. This failure of PageRank reveals that the static approach to information filtering is inappropriate for a broad class of growing systems, and suggest that time-dependent algorithms that are based on the temporal linking patterns of these systems are needed to better rank the nodes.

  9. Promzea: a pipeline for discovery of co-regulatory motifs in maize and other plant species and its application to the anthocyanin and phlobaphene biosynthetic pathways and the Maize Development Atlas.

    Science.gov (United States)

    Liseron-Monfils, Christophe; Lewis, Tim; Ashlock, Daniel; McNicholas, Paul D; Fauteux, François; Strömvik, Martina; Raizada, Manish N

    2013-03-15

    The discovery of genetic networks and cis-acting DNA motifs underlying their regulation is a major objective of transcriptome studies. The recent release of the maize genome (Zea mays L.) has facilitated in silico searches for regulatory motifs. Several algorithms exist to predict cis-acting elements, but none have been adapted for maize. A benchmark data set was used to evaluate the accuracy of three motif discovery programs: BioProspector, Weeder and MEME. Analysis showed that each motif discovery tool had limited accuracy and appeared to retrieve a distinct set of motifs. Therefore, using the benchmark, statistical filters were optimized to reduce the false discovery ratio, and then remaining motifs from all programs were combined to improve motif prediction. These principles were integrated into a user-friendly pipeline for motif discovery in maize called Promzea, available at http://www.promzea.org and on the Discovery Environment of the iPlant Collaborative website. Promzea was subsequently expanded to include rice and Arabidopsis. Within Promzea, a user enters cDNA sequences or gene IDs; corresponding upstream sequences are retrieved from the maize genome. Predicted motifs are filtered, combined and ranked. Promzea searches the chosen plant genome for genes containing each candidate motif, providing the user with the gene list and corresponding gene annotations. Promzea was validated in silico using a benchmark data set: the Promzea pipeline showed a 22% increase in nucleotide sensitivity compared to the best standalone program tool, Weeder, with equivalent nucleotide specificity. Promzea was also validated by its ability to retrieve the experimentally defined binding sites of transcription factors that regulate the maize anthocyanin and phlobaphene biosynthetic pathways. Promzea predicted additional promoter motifs, and genome-wide motif searches by Promzea identified 127 non-anthocyanin/phlobaphene genes that each contained all five predicted promoter

  10. RANK/RANK-Ligand/OPG: Ein neuer Therapieansatz in der Osteoporosebehandlung

    Directory of Open Access Journals (Sweden)

    Preisinger E

    2007-01-01

    Full Text Available Die Erforschung der Kopplungsmechanismen zur Osteoklastogenese, Knochenresorption und Remodellierung eröffnete neue mögliche Therapieansätze in der Behandlung der Osteoporose. Eine Schlüsselrolle beim Knochenabbau spielt der RANK- ("receptor activator of nuclear factor (NF- κB"- Ligand (RANKL. Durch die Bindung von RANKL an den Rezeptor RANK wird die Knochenresorption eingeleitet. OPG (Osteoprotegerin sowie der für den klinischen Gebrauch entwickelte humane monoklonale Antikörper (IgG2 Denosumab blockieren die Bindung von RANK-Ligand an RANK und verhindern den Knochenabbau.

  11. Regulation and function of the CD3¿ DxxxLL motif: a binding site for adaptor protein-1 and adaptor protein-2 in vitro

    DEFF Research Database (Denmark)

    Dietrich, J; Kastrup, J; Nielsen, B L

    1997-01-01

    /CD3gamma chimeras; and in vitro by binding CD3gamma peptides to clathrin-coated vesicle adaptor proteins (APs). We find that the CD3gamma D127xxxLL131/132 sequence represents one united motif for binding of both AP-1 and AP-2, and that this motif functions as an active sorting motif in monomeric CD4...... and for AP binding in vitro. Furthermore, we provide evidence indicating that phosphorylation of CD3gamma S126 in the context of the complete TCR induces a conformational change that exposes the DxxxLL sequence for AP binding. Exposure of the DxxxLL motif causes an increase in the TCR internalization rate...

  12. Learning to rank figures within a biomedical article.

    Directory of Open Access Journals (Sweden)

    Feifan Liu

    Full Text Available Hundreds of millions of figures are available in biomedical literature, representing important biomedical experimental evidence. This ever-increasing sheer volume has made it difficult for scientists to effectively and accurately access figures of their interest, the process of which is crucial for validating research facts and for formulating or testing novel research hypotheses. Current figure search applications can't fully meet this challenge as the "bag of figures" assumption doesn't take into account the relationship among figures. In our previous study, hundreds of biomedical researchers have annotated articles in which they serve as corresponding authors. They ranked each figure in their paper based on a figure's importance at their discretion, referred to as "figure ranking". Using this collection of annotated data, we investigated computational approaches to automatically rank figures. We exploited and extended the state-of-the-art listwise learning-to-rank algorithms and developed a new supervised-learning model BioFigRank. The cross-validation results show that BioFigRank yielded the best performance compared with other state-of-the-art computational models, and the greedy feature selection can further boost the ranking performance significantly. Furthermore, we carry out the evaluation by comparing BioFigRank with three-level competitive domain-specific human experts: (1 First Author, (2 Non-Author-In-Domain-Expert who is not the author nor co-author of an article but who works in the same field of the corresponding author of the article, and (3 Non-Author-Out-Domain-Expert who is not the author nor co-author of an article and who may or may not work in the same field of the corresponding author of an article. Our results show that BioFigRank outperforms Non-Author-Out-Domain-Expert and performs as well as Non-Author-In-Domain-Expert. Although BioFigRank underperforms First Author, since most biomedical researchers are either in- or

  13. Learning to rank figures within a biomedical article.

    Science.gov (United States)

    Liu, Feifan; Yu, Hong

    2014-01-01

    Hundreds of millions of figures are available in biomedical literature, representing important biomedical experimental evidence. This ever-increasing sheer volume has made it difficult for scientists to effectively and accurately access figures of their interest, the process of which is crucial for validating research facts and for formulating or testing novel research hypotheses. Current figure search applications can't fully meet this challenge as the "bag of figures" assumption doesn't take into account the relationship among figures. In our previous study, hundreds of biomedical researchers have annotated articles in which they serve as corresponding authors. They ranked each figure in their paper based on a figure's importance at their discretion, referred to as "figure ranking". Using this collection of annotated data, we investigated computational approaches to automatically rank figures. We exploited and extended the state-of-the-art listwise learning-to-rank algorithms and developed a new supervised-learning model BioFigRank. The cross-validation results show that BioFigRank yielded the best performance compared with other state-of-the-art computational models, and the greedy feature selection can further boost the ranking performance significantly. Furthermore, we carry out the evaluation by comparing BioFigRank with three-level competitive domain-specific human experts: (1) First Author, (2) Non-Author-In-Domain-Expert who is not the author nor co-author of an article but who works in the same field of the corresponding author of the article, and (3) Non-Author-Out-Domain-Expert who is not the author nor co-author of an article and who may or may not work in the same field of the corresponding author of an article. Our results show that BioFigRank outperforms Non-Author-Out-Domain-Expert and performs as well as Non-Author-In-Domain-Expert. Although BioFigRank underperforms First Author, since most biomedical researchers are either in- or out

  14. Dimensionality of social networks using motifs and eigenvalues.

    Directory of Open Access Journals (Sweden)

    Anthony Bonato

    Full Text Available We consider the dimensionality of social networks, and develop experiments aimed at predicting that dimension. We find that a social network model with nodes and links sampled from an m-dimensional metric space with power-law distributed influence regions best fits samples from real-world networks when m scales logarithmically with the number of nodes of the network. This supports a logarithmic dimension hypothesis, and we provide evidence with two different social networks, Facebook and LinkedIn. Further, we employ two different methods for confirming the hypothesis: the first uses the distribution of motif counts, and the second exploits the eigenvalue distribution.

  15. Hybrid DNA i-motif: Aminoethylprolyl-PNA (pC5) enhance the stability of DNA (dC5) i-motif structure.

    Science.gov (United States)

    Gade, Chandrasekhar Reddy; Sharma, Nagendra K

    2017-12-15

    This report describes the synthesis of C-rich sequence, cytosine pentamer, of aep-PNA and its biophysical studies for the formation of hybrid DNA:aep-PNAi-motif structure with DNA cytosine pentamer (dC 5 ) under acidic pH conditions. Herein, the CD/UV/NMR/ESI-Mass studies strongly support the formation of stable hybrid DNA i-motif structure with aep-PNA even near acidic conditions. Hence aep-PNA C-rich sequence cytosine could be considered as potential DNA i-motif stabilizing agents in vivo conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Genetic interaction motif finding by expectation maximization – a novel statistical model for inferring gene modules from synthetic lethality

    Directory of Open Access Journals (Sweden)

    Ye Ping

    2005-12-01

    Full Text Available Abstract Background Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. Results We have developed Genetic Interaction Motif Finding (GIMF, an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast. Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. Conclusion GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic

  17. Forensic botany: species identification of botanical trace evidence using a multigene barcoding approach.

    Science.gov (United States)

    Ferri, Gianmarco; Alù, Milena; Corradini, Beatrice; Beduschi, Giovanni

    2009-09-01

    Forensic botany can provide significant supporting evidence during criminal investigations. However, it is still an underutilized field of investigation with its most common application limited to identifying specific as well as suspected illegal plants. The ubiquitous presence of plant species can be useful in forensics, but the absence of an accurate identification system remains the major obstacle to the present inability to routinely and correctly identify trace botanical evidence. Many plant materials cannot be identified and differentiated to the species level by traditional morphological characteristics when botanical specimens are degraded and lack physical features. By taking advantage of a universal barcode system, DNA sequencing, and other biomolecular techniques used routinely in forensic investigations, two chloroplast DNA regions were evaluated for their use as "barcoding" markers for plant identification in the field of forensics. We therefore investigated the forensic use of two non-coding plastid regions, psbA-trnH and trnL-trnF, to create a multimarker system for species identification that could be useful throughout the plant kingdom. The sequences from 63 plants belonging to our local flora were submitted and registered on the GenBank database. Sequence comparison to set up the level of identification (species, genus, or family) through Blast algorithms allowed us to assess the suitability of this method. The results confirmed the effectiveness of our botanic universal multimarker assay in forensic investigations.

  18. Iris small break loca phenomena identification and ranking table (PIRT)

    International Nuclear Information System (INIS)

    Larson, T.K.; Moody, F.J.; Wilson, G.E.; Brown, W.L.; Frepoli, C.; Hartz, J.; Woods, B.G.; Oriani, L.

    2007-01-01

    The international reactor innovative and secure (IRIS) is a modular pressurized water reactor with an integral configuration (all primary system components - reactor core, internals, pumps, steam generators, pressurizer, and control rod drive mechanisms - are inside the reactor vessel). The IRIS plant conceptual design was completed in 2001 and the preliminary design is currently underway. The pre-application licensing process with the United States Nuclear Regulatory Commission (USNRC) started in October 2002. The first line of defense in IRIS is to eliminate event initiators that could potentially lead to core damage. If it is not possible to eliminate certain accidents altogether, then the design inherently reduces their consequences and/or decreases their probability of occurring. One of the most obvious advantages of the IRIS Safety-by-Design TM approach is the elimination of large break loss-of-coolant accidents (LBLOCAs), since no large primary penetrations of the reactor vessel or large loop piping exist. While the IRIS Safety-by-Design TM approach is a logical step in the effort to produce advanced reactors, the desired advances in safety must still be demonstrated in the licensing arena. With the elimination of LBLOCA, an important next consideration is to show the IRIS design fulfills the promise of increased safety also for small break LOCAs (SBLOCAs). Accordingly, the SBLOCA phenomena identification and ranking table (PIRT) project was established. The primary objective of the IRIS SBLOCA PIRT project was to identify the relative importance of phenomena in the IRIS response to SBLOCAs. This relative importance, coupled with the current relative state of knowledge for the phenomena, provides a framework for the planning of the continued experimental and analytical efforts. To satisfy the SBLOCA PIRT project objectives, Westinghouse organized an expert panel whose members were carefully selected to insure that the PIRT results reflect internationally

  19. Network motif frequency vectors reveal evolving metabolic network organisation.

    Science.gov (United States)

    Pearcy, Nicole; Crofts, Jonathan J; Chuzhanova, Nadia

    2015-01-01

    At the systems level many organisms of interest may be described by their patterns of interaction, and as such, are perhaps best characterised via network or graph models. Metabolic networks, in particular, are fundamental to the proper functioning of many important biological processes, and thus, have been widely studied over the past decade or so. Such investigations have revealed a number of shared topological features, such as a short characteristic path-length, large clustering coefficient and hierarchical modular structure. However, the extent to which evolutionary and functional properties of metabolism manifest via this underlying network architecture remains unclear. In this paper, we employ a novel graph embedding technique, based upon low-order network motifs, to compare metabolic network structure for 383 bacterial species categorised according to a number of biological features. In particular, we introduce a new global significance score which enables us to quantify important evolutionary relationships that exist between organisms and their physical environments. Using this new approach, we demonstrate a number of significant correlations between environmental factors, such as growth conditions and habitat variability, and network motif structure, providing evidence that organism adaptability leads to increased complexities in the resultant metabolic networks.

  20. Characterizing Microseismicity at the Newberry Volcano Geothermal Site using PageRank

    Science.gov (United States)

    Aguiar, A. C.; Myers, S. C.

    2015-12-01

    The Newberry Volcano, within the Deschutes National Forest in Oregon, has been designated as a candidate site for the Department of Energy's Frontier Observatory for Research in Geothermal Energy (FORGE) program. This site was stimulated using high-pressure fluid injection during the fall of 2012, which generated several hundred microseismic events. Exploring the spatial and temporal development of microseismicity is key to understanding how subsurface stimulation modifies stress, fractures rock, and increases permeability. We analyze Newberry seismicity using both surface and borehole seismometers from the AltaRock and LLNL seismic networks. For our analysis we adapt PageRank, Google's initial search algorithm, to evaluate microseismicity during the 2012 stimulation. PageRank is a measure of connectivity, where higher ranking represents highly connected windows. In seismic applications connectivity is measured by the cross correlation of 2 time windows recorded on a common seismic station and channel. Aguiar and Beroza (2014) used PageRank based on cross correlation to detect low-frequency earthquakes, which are highly repetitive but difficult to detect. We expand on this application by using PageRank to define signal-correlation topology for micro-earthquakes, including the identification of signals that are connected to the largest number of other signals. We then use this information to create signal families and compare PageRank families to the spatial and temporal proximity of associated earthquakes. Studying signal PageRank will potentially allow us to efficiently group earthquakes with similar physical characteristics, such as focal mechanisms and stress drop. Our ultimate goal is to determine whether changes in the state of stress and/or changes in the generation of subsurface fracture networks can be detected using PageRank topology. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under

  1. Purification and functional motifs of the recombinant ATPase of orf virus.

    Science.gov (United States)

    Lin, Fong-Yuan; Chan, Kun-Wei; Wang, Chi-Young; Wong, Min-Liang; Hsu, Wei-Li

    2011-10-01

    Our previous study showed that the recombinant ATPase encoded by the A32L gene of orf virus displayed ATP hydrolysis activity as predicted from its amino acids sequence. This viral ATPase contains four known functional motifs (motifs I-IV) and a novel AYDG motif; they are essential for ATP hydrolysis reaction by binding ATP and magnesium ions. The motifs I and II correspond with the Walker A and B motifs of the typical ATPase, respectively. To examine the biochemical roles of these five conserved motifs, recombinant ATPases of five deletion mutants derived from the Taiping strain were expressed and purified. Their ATPase functions were assayed and compared with those of two wild type strains, Taiping and Nantou isolated in Taiwan. Our results showed that deletions at motifs I-III or IV exhibited lower activity than that of the wild type. Interestingly, deletion of AYDG motif decreased the ATPase activity more significantly than those of motifs I-IV deletions. Divalent ions such as magnesium and calcium were essential for ATPase activity. Moreover, our recombinant proteins of orf virus also demonstrated GTPase activity, though weaker than the original ATPase activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. A phosphorylation-motif for tuneable helix stabilisation in intrinsically disordered proteins - Lessons from the sodium proton exchanger 1 (NHE1)

    DEFF Research Database (Denmark)

    Hendus-Altenburger, Ruth; Lambrughi, Matteo; Terkelsen, Thilde Bagger

    2017-01-01

    ). Using NMR spectroscopy, we found that two out of those six phosphorylation sites had a stabilizing effect on transient helices. One of these was further investigated by circular dichroism and NMR spectroscopy as well as by molecular dynamic simulations, which confirmed the stabilizing effect......-spread role in phosphorylation-mediated regulation of intrinsically disordered proteins. The identification of such motifs is important for understanding the molecular mechanism of cellular signalling, and is crucial for the development of predictors for the structural effect of phosphorylation; a tool......Intrinsically disordered proteins (IDPs) are involved in many pivotal cellular processes including phosphorylation and signalling. The structural and functional effects of phosphorylation of IDPs remain poorly understood and difficult to predict. Thus, a need exists to identify motifs that confer...

  3. Molecular Detection, Phylogenetic Analysis, and Identification of Transcription Motifs in Feline Leukemia Virus from Naturally Infected Cats in Malaysia

    Directory of Open Access Journals (Sweden)

    Faruku Bande

    2014-01-01

    Full Text Available A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats. Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search. Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39 were confirmed positive with nested PCR. FeLV proviral DNA was detected in 38 (97.3% of p27-antigen negative samples. Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%. Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2% sharing similarity with FeLV-K01803 and fewer isolates (13.8% with FeLV-GM1 strain. Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region. The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats. Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate. This study provides the first molecular based information on FeLV in Malaysia. Additionally, different enhancer motifs likely associated with FeLV related pathogenesis have been identified.

  4. An experimental test of a fundamental food web motif.

    Science.gov (United States)

    Rip, Jason M K; McCann, Kevin S; Lynn, Denis H; Fawcett, Sonia

    2010-06-07

    Large-scale changes to the world's ecosystem are resulting in the deterioration of biostructure-the complex web of species interactions that make up ecological communities. A difficult, yet crucial task is to identify food web structures, or food web motifs, that are the building blocks of this baroque network of interactions. Once identified, these food web motifs can then be examined through experiments and theory to provide mechanistic explanations for how structure governs ecosystem stability. Here, we synthesize recent ecological research to show that generalist consumers coupling resources with different interaction strengths, is one such motif. This motif amazingly occurs across an enormous range of spatial scales, and so acts to distribute coupled weak and strong interactions throughout food webs. We then perform an experiment that illustrates the importance of this motif to ecological stability. We find that weak interactions coupled to strong interactions by generalist consumers dampen strong interaction strengths and increase community stability. This study takes a critical step by isolating a common food web motif and through clear, experimental manipulation, identifies the fundamental stabilizing consequences of this structure for ecological communities.

  5. Insights into the molecular evolution of the PDZ/LIM family and identification of a novel conserved protein motif.

    Directory of Open Access Journals (Sweden)

    Aartjan J W Te Velthuis

    Full Text Available The PDZ and LIM domain-containing protein family is encoded by a diverse group of genes whose phylogeny has currently not been analyzed. In mammals, ten genes are found that encode both a PDZ- and one or several LIM-domains. These genes are: ALP, RIL, Elfin (CLP36, Mystique, Enigma (LMP-1, Enigma homologue (ENH, ZASP (Cypher, Oracle, LMO7 and the two LIM domain kinases (LIMK1 and LIMK2. As conventional alignment and phylogenetic procedures of full-length sequences fell short of elucidating the evolutionary history of these genes, we started to analyze the PDZ and LIM domain sequences themselves. Using information from most sequenced eukaryotic lineages, our phylogenetic analysis is based on full-length cDNA-, EST-derived- and genomic- PDZ and LIM domain sequences of over 25 species, ranging from yeast to humans. Plant and protozoan homologs were not found. Our phylogenetic analysis identifies a number of domain duplication and rearrangement events, and shows a single convergent event during evolution of the PDZ/LIM family. Further, we describe the separation of the ALP and Enigma subfamilies in lower vertebrates and identify a novel consensus motif, which we call 'ALP-like motif' (AM. This motif is highly-conserved between ALP subfamily proteins of diverse organisms. We used here a combinatorial approach to define the relation of the PDZ and LIM domain encoding genes and to reconstruct their phylogeny. This analysis allowed us to classify the PDZ/LIM family and to suggest a meaningful model for the molecular evolution of the diverse gene architectures found in this multi-domain family.

  6. Research of Subgraph Estimation Page Rank Algorithm for Web Page Rank

    Directory of Open Access Journals (Sweden)

    LI Lan-yin

    2017-04-01

    Full Text Available The traditional PageRank algorithm can not efficiently perform large data Webpage scheduling problem. This paper proposes an accelerated algorithm named topK-Rank,which is based on PageRank on the MapReduce platform. It can find top k nodes efficiently for a given graph without sacrificing accuracy. In order to identify top k nodes,topK-Rank algorithm prunes unnecessary nodes and edges in each iteration to dynamically construct subgraphs,and iteratively estimates lower/upper bounds of PageRank scores through subgraphs. Theoretical analysis shows that this method guarantees result exactness. Experiments show that topK-Rank algorithm can find k nodes much faster than the existing approaches.

  7. Mechanisms of zero-lag synchronization in cortical motifs.

    Directory of Open Access Journals (Sweden)

    Leonardo L Gollo

    2014-04-01

    Full Text Available Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of "dynamical relaying"--a mechanism that relies on a specific network motif--has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair--a "resonance pair"--plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying from those that do not (such as the common driving triad. Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain.

  8. Multimodal biometric system using rank-level fusion approach.

    Science.gov (United States)

    Monwar, Md Maruf; Gavrilova, Marina L

    2009-08-01

    In many real-world applications, unimodal biometric systems often face significant limitations due to sensitivity to noise, intraclass variability, data quality, nonuniversality, and other factors. Attempting to improve the performance of individual matchers in such situations may not prove to be highly effective. Multibiometric systems seek to alleviate some of these problems by providing multiple pieces of evidence of the same identity. These systems help achieve an increase in performance that may not be possible using a single-biometric indicator. This paper presents an effective fusion scheme that combines information presented by multiple domain experts based on the rank-level fusion integration method. The developed multimodal biometric system possesses a number of unique qualities, starting from utilizing principal component analysis and Fisher's linear discriminant methods for individual matchers (face, ear, and signature) identity authentication and utilizing the novel rank-level fusion method in order to consolidate the results obtained from different biometric matchers. The ranks of individual matchers are combined using the highest rank, Borda count, and logistic regression approaches. The results indicate that fusion of individual modalities can improve the overall performance of the biometric system, even in the presence of low quality data. Insights on multibiometric design using rank-level fusion and its performance on a variety of biometric databases are discussed in the concluding section.

  9. Transduction motif analysis of gastric cancer based on a human signaling network

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  10. A multi-criteria decision analysis approach for importance identification and ranking of network components

    International Nuclear Information System (INIS)

    Almoghathawi, Yasser; Barker, Kash; Rocco, Claudio M.; Nicholson, Charles D.

    2017-01-01

    Analyzing network vulnerability is a key element of network planning in order to be prepared for any disruptive event that might impact the performance of the network. Hence, many importance measures have been proposed to identify the important components in a network with respect to vulnerability and rank them accordingly based on individual importance measure. However, in this paper, we propose a new approach to identify the most important network components based on multiple importance measures using a multi criteria decision making (MCDM) method, namely the technique for order performance by similarity to ideal solution (TOPSIS), able to take into account the preferences of decision-makers. We consider multiple edge-specific flow-based importance measures provided as the multiple criteria of a network where the alternatives are the edges. Accordingly, TOPSIS is used to rank the edges of the network based on their importance considering multiple different importance measures. The proposed approach is illustrated through different networks with different densities along with the effects of weighs. - Highlights: • We integrate several perspectives on network vulnerability to generate a component importance ranking. • We apply these measures to determine the importance of edges after disruptions. • Networks of varying size and density are explored.

  11. Identification of Predictive Cis-Regulatory Elements Using a Discriminative Objective Function and a Dynamic Search Space.

    Directory of Open Access Journals (Sweden)

    Rahul Karnik

    Full Text Available The generation of genomic binding or accessibility data from massively parallel sequencing technologies such as ChIP-seq and DNase-seq continues to accelerate. Yet state-of-the-art computational approaches for the identification of DNA binding motifs often yield motifs of weak predictive power. Here we present a novel computational algorithm called MotifSpec, designed to find predictive motifs, in contrast to over-represented sequence elements. The key distinguishing feature of this algorithm is that it uses a dynamic search space and a learned threshold to find discriminative motifs in combination with the modeling of motifs using a full PWM (position weight matrix rather than k-mer words or regular expressions. We demonstrate that our approach finds motifs corresponding to known binding specificities in several mammalian ChIP-seq datasets, and that our PWMs classify the ChIP-seq signals with accuracy comparable to, or marginally better than motifs from the best existing algorithms. In other datasets, our algorithm identifies novel motifs where other methods fail. Finally, we apply this algorithm to detect motifs from expression datasets in C. elegans using a dynamic expression similarity metric rather than fixed expression clusters, and find novel predictive motifs.

  12. Characterizing Motif Dynamics of Electric Brain Activity Using Symbolic Analysis

    Directory of Open Access Journals (Sweden)

    Massimiliano Zanin

    2014-10-01

    Full Text Available Motifs are small recurring circuits of interactions which constitute the backbone of networked systems. Characterizing motif dynamics is therefore key to understanding the functioning of such systems. Here we propose a method to define and quantify the temporal variability and time scales of electroencephalogram (EEG motifs of resting brain activity. Given a triplet of EEG sensors, links between them are calculated by means of linear correlation; each pattern of links (i.e., each motif is then associated to a symbol, and its appearance frequency is analyzed by means of Shannon entropy. Our results show that each motif becomes observable with different coupling thresholds and evolves at its own time scale, with fronto-temporal sensors emerging at high thresholds and changing at fast time scales, and parietal ones at low thresholds and changing at slower rates. Finally, while motif dynamics differed across individuals, for each subject, it showed robustness across experimental conditions, indicating that it could represent an individual dynamical signature.

  13. Discriminative motif discovery via simulated evolution and random under-sampling.

    Directory of Open Access Journals (Sweden)

    Tao Song

    Full Text Available Conserved motifs in biological sequences are closely related to their structure and functions. Recently, discriminative motif discovery methods have attracted more and more attention. However, little attention has been devoted to the data imbalance problem, which is one of the main reasons affecting the performance of the discriminative models. In this article, a simulated evolution method is applied to solve the multi-class imbalance problem at the stage of data preprocessing, and at the stage of Hidden Markov Models (HMMs training, a random under-sampling method is introduced for the imbalance between the positive and negative datasets. It is shown that, in the task of discovering targeting motifs of nine subcellular compartments, the motifs found by our method are more conserved than the methods without considering data imbalance problem and recover the most known targeting motifs from Minimotif Miner and InterPro. Meanwhile, we use the found motifs to predict protein subcellular localization and achieve higher prediction precision and recall for the minority classes.

  14. Discriminative motif discovery via simulated evolution and random under-sampling.

    Science.gov (United States)

    Song, Tao; Gu, Hong

    2014-01-01

    Conserved motifs in biological sequences are closely related to their structure and functions. Recently, discriminative motif discovery methods have attracted more and more attention. However, little attention has been devoted to the data imbalance problem, which is one of the main reasons affecting the performance of the discriminative models. In this article, a simulated evolution method is applied to solve the multi-class imbalance problem at the stage of data preprocessing, and at the stage of Hidden Markov Models (HMMs) training, a random under-sampling method is introduced for the imbalance between the positive and negative datasets. It is shown that, in the task of discovering targeting motifs of nine subcellular compartments, the motifs found by our method are more conserved than the methods without considering data imbalance problem and recover the most known targeting motifs from Minimotif Miner and InterPro. Meanwhile, we use the found motifs to predict protein subcellular localization and achieve higher prediction precision and recall for the minority classes.

  15. Improved i-motif thermal stability by insertion of anthraquinone monomers

    DEFF Research Database (Denmark)

    Gouda, Alaa S; Amine, Mahasen S.; Pedersen, Erik Bjerregaard

    2017-01-01

    In order to gain insight into how to improve thermal stability of i-motifs when used in the context of biomedical and nanotechnological applications, novel anthraquinone-modified i-motifs were synthesized by insertion of 1,8-, 1,4-, 1,5- and 2,6-disubstituted anthraquinone monomers into the TAA...... loops of a 22mer cytosine-rich human telomeric DNA sequence. The influence of the four anthraquinone linkers on the i-motif thermal stability was investigated at 295 nm and pH 5.5. Anthraquinone monomers modulate the i-motif stability in a position-depending manner and the modulation also depends...... unlocked nucleic acid monomers or twisted intercalating nucleic acid. The 2,6-disubstituted anthraquinone linker replacing T10 enabled a significant increase of i-motif thermal melting by 8.2 °C. A substantial increase of 5.0 °C in i-motif thermal melting was recorded when both A6 and T16 were modified...

  16. Marine Hydrokinetic Energy Site Identification and Ranking Methodology Part I: Wave Energy

    Energy Technology Data Exchange (ETDEWEB)

    Kilcher, Levi [National Renewable Energy Lab. (NREL), Golden, CO (United States); Thresher, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-10-01

    Marine hydrokinetic energy is a promising and growing piece of the renewable energy sector that offers high predictability and additional energy sources for a diversified energy economy. This report investigates the market opportunities for wave energy along the U.S. coastlines. It is part one of a two-part investigation into the United State's two largest marine hydrokinetic resources (wave and tidal). Wave energy technology is still an emerging form of renewable energy for which large-scale, grid-connected project costs are currently poorly defined. Ideally, device designers would like to know the resource conditions at economical project sites so they can optimize device designs. On the other hand, project developers need detailed device cost data to identify sites where projects are economical. That is, device design and siting are, to some extent, a coupled problem. This work describes a methodology for identifying likely deployment locations based on a set of criteria that wave energy experts in industry, academia, and national laboratories agree are likely to be important factors for all technology types. This work groups the data for the six criteria into 'locales' that are defined as the smaller of either the local transmission grid or a state boundary. The former applies to U.S. islands (e.g., Hawaii, American Samoa) and rural villages (e.g., in Alaska); the latter applies to states in the contiguous United States. These data are then scored from 0 to 10 according to scoring functions that were developed with input from wave energy industry and academic experts. The scores are aggregated using a simple product method that includes a weighting factor for each criterion. This work presents two weighting scenarios: a long-term scenario that does not include energy price (weighted zero) and a near term scenario that includes energy price. The aggregated scores are then used to produce ranked lists of likely deployment locales. In both scenarios

  17. The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

    International Nuclear Information System (INIS)

    Kwon, Oh Hyung; Lee, Chong-Kil; Lee, Young Ik; Paik, Sang-Gi; Lee, Hyun-Jun

    2005-01-01

    Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor κB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1 -/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation

  18. Wilcoxon's signed-rank statistic: what null hypothesis and why it matters.

    Science.gov (United States)

    Li, Heng; Johnson, Terri

    2014-01-01

    In statistical literature, the term 'signed-rank test' (or 'Wilcoxon signed-rank test') has been used to refer to two distinct tests: a test for symmetry of distribution and a test for the median of a symmetric distribution, sharing a common test statistic. To avoid potential ambiguity, we propose to refer to those two tests by different names, as 'test for symmetry based on signed-rank statistic' and 'test for median based on signed-rank statistic', respectively. The utility of such terminological differentiation should become evident through our discussion of how those tests connect and contrast with sign test and one-sample t-test. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  19. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

    Directory of Open Access Journals (Sweden)

    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

  20. Sparse structure regularized ranking

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-04-17

    Learning ranking scores is critical for the multimedia database retrieval problem. In this paper, we propose a novel ranking score learning algorithm by exploring the sparse structure and using it to regularize ranking scores. To explore the sparse structure, we assume that each multimedia object could be represented as a sparse linear combination of all other objects, and combination coefficients are regarded as a similarity measure between objects and used to regularize their ranking scores. Moreover, we propose to learn the sparse combination coefficients and the ranking scores simultaneously. A unified objective function is constructed with regard to both the combination coefficients and the ranking scores, and is optimized by an iterative algorithm. Experiments on two multimedia database retrieval data sets demonstrate the significant improvements of the propose algorithm over state-of-the-art ranking score learning algorithms.

  1. Computational analyses of synergism in small molecular network motifs.

    Directory of Open Access Journals (Sweden)

    Yili Zhang

    2014-03-01

    Full Text Available Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli. The present study investigates how variations in pairs of parameters affect responses in a series of ten common network motifs, identifying concurrent variations that act synergistically (or antagonistically to alter the responses of the motifs to stimuli. Synergism (or antagonism was quantified using degrees of nonlinear blending and additive synergism. Simulations identified concurrent variations that maximized synergism, and examined the ways in which it was affected by stimulus protocols and the architecture of a motif. Only a subset of architectures exhibited synergism following paired changes in parameters. The approach was then applied to a model describing interlocked feedback loops governing the synthesis of the CREB1 and CREB2 transcription factors. The effects of motifs on synergism for this biologically realistic model were consistent with those for the abstract models of single motifs. These results have implications for the rational design of combination drug therapies with the potential for synergistic interactions.

  2. Phyloproteomic Analysis of 11780 Six-Residue-Long Motifs Occurrences

    Directory of Open Access Journals (Sweden)

    O. V. Galzitskaya

    2015-01-01

    Full Text Available How is it possible to find good traits for phylogenetic reconstructions? Here, we present a new phyloproteomic criterion that is an occurrence of simple motifs which can be imprints of evolution history. We studied the occurrences of 11780 six-residue-long motifs consisting of two randomly located amino acids in 97 eukaryotic and 25 bacterial proteomes. For all eukaryotic proteomes, with the exception of the Amoebozoa, Stramenopiles, and Diplomonadida kingdoms, the number of proteins containing the motifs from the first group (one of the two amino acids occurs once at the terminal position made about 20%; in the case of motifs from the second (one of two amino acids occurs one time within the pattern and third (the two amino acids occur randomly groups, 30% and 50%, respectively. For bacterial proteomes, this relationship was 10%, 27%, and 63%, respectively. The matrices of correlation coefficients between numbers of proteins where a motif from the set of 11780 motifs appears at least once in 9 kingdoms and 5 phyla of bacteria were calculated. Among the correlation coefficients for eukaryotic proteomes, the correlation between the animal and fungi kingdoms (0.62 is higher than between fungi and plants (0.54. Our study provides support that animals and fungi are sibling kingdoms. Comparison of the frequencies of six-residue-long motifs in different proteomes allows obtaining phylogenetic relationships based on similarities between these frequencies: the Diplomonadida kingdoms are more close to Bacteria than to Eukaryota; Stramenopiles and Amoebozoa are more close to each other than to other kingdoms of Eukaryota.

  3. Identification and analysis of an efficient dicot constitutive promoter from tomato

    International Nuclear Information System (INIS)

    Bacha, S.; Khatoon, A.; Asif, M.; Bashir, A.

    2015-01-01

    The regulatory sequence of sucrose synthase (susy) was explored in HTGS and screened using various bioinformatics tools for promoter prediction and identification of functional regulatory motifs. Transcription start site (TSS) was predicted in the promoter sequence. Species specific motifs were identified by using Plant PAN database. The Plant Care predicted various light responsive, hormone inducible and tissue specific motifs in the full length promoter which may be essential for the constitutive expression governed by this promoter. Full length susy promoter isolated from tomato (Solanum lycopersicum) drove maximum transient expression of GUS gene in various tissues of tobacco, cotton and peas. The susy promoter identified and analyzed in this study is suitable for transgene expression in economically important agricultural crops, especially to avoid strong over-expression. (author)

  4. A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.

    Science.gov (United States)

    Kalay, E; de Brouwer, A P M; Caylan, R; Nabuurs, S B; Wollnik, B; Karaguzel, A; Heister, J G A M; Erdol, H; Cremers, F P M; Cremers, C W R J; Brunner, H G; Kremer, H

    2005-12-01

    Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.

  5. Low-rank coal research

    Energy Technology Data Exchange (ETDEWEB)

    Weber, G. F.; Laudal, D. L.

    1989-01-01

    This work is a compilation of reports on ongoing research at the University of North Dakota. Topics include: Control Technology and Coal Preparation Research (SO{sub x}/NO{sub x} control, waste management), Advanced Research and Technology Development (turbine combustion phenomena, combustion inorganic transformation, coal/char reactivity, liquefaction reactivity of low-rank coals, gasification ash and slag characterization, fine particulate emissions), Combustion Research (fluidized bed combustion, beneficiation of low-rank coals, combustion characterization of low-rank coal fuels, diesel utilization of low-rank coals), Liquefaction Research (low-rank coal direct liquefaction), and Gasification Research (hydrogen production from low-rank coals, advanced wastewater treatment, mild gasification, color and residual COD removal from Synfuel wastewaters, Great Plains Gasification Plant, gasifier optimization).

  6. Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

    Science.gov (United States)

    Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

    2015-06-01

    Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A human fecal contamination index for ranking impaired ...

    Science.gov (United States)

    Human fecal pollution of surface water remains a public health concern worldwide. As a result, there is a growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for recreational water quality risk management. The transition from a research subject to a management tool requires the integration of standardized water sampling, laboratory, and data analysis procedures. In this study, a standardized HF183/BacR287 qPCR method was combined with a water sampling strategy and Bayesian data algorithm to establish a human fecal contamination index that can be used to rank impaired recreational water sites polluted with human waste. Stability and bias of index predictions were investigated under various parameters including siteswith different pollution levels, sampling period time range (1-15 weeks), and number of qPCR replicates per sample (2-14 replicates). Sensitivity analyses were conducted with simulated data sets (100 iterations) seeded with HF183/BacR287 qPCR laboratory measurements from water samples collected from three Southern California sites (588 qPCR measurements). Findings suggest that site ranking is feasible and that all parameters tested influence stability and bias in human fecal contamination indexscoring. Trends identified by sensitivity analyses will provide managers with the information needed to design and conduct field studies to rank impaired recreational water sites based

  8. Methods and statistics for combining motif match scores.

    Science.gov (United States)

    Bailey, T L; Gribskov, M

    1998-01-01

    Position-specific scoring matrices are useful for representing and searching for protein sequence motifs. A sequence family can often be described by a group of one or more motifs, and an effective search must combine the scores for matching a sequence to each of the motifs in the group. We describe three methods for combining match scores and estimating the statistical significance of the combined scores and evaluate the search quality (classification accuracy) and the accuracy of the estimate of statistical significance of each. The three methods are: 1) sum of scores, 2) sum of reduced variates, 3) product of score p-values. We show that method 3) is superior to the other two methods in both regards, and that combining motif scores indeed gives better search accuracy. The MAST sequence homology search algorithm utilizing the product of p-values scoring method is available for interactive use and downloading at URL http:/(/)www.sdsc.edu/MEME.

  9. MOCCS: Clarifying DNA-binding motif ambiguity using ChIP-Seq data.

    Science.gov (United States)

    Ozaki, Haruka; Iwasaki, Wataru

    2016-08-01

    As a key mechanism of gene regulation, transcription factors (TFs) bind to DNA by recognizing specific short sequence patterns that are called DNA-binding motifs. A single TF can accept ambiguity within its DNA-binding motifs, which comprise both canonical (typical) and non-canonical motifs. Clarification of such DNA-binding motif ambiguity is crucial for revealing gene regulatory networks and evaluating mutations in cis-regulatory elements. Although chromatin immunoprecipitation sequencing (ChIP-seq) now provides abundant data on the genomic sequences to which a given TF binds, existing motif discovery methods are unable to directly answer whether a given TF can bind to a specific DNA-binding motif. Here, we report a method for clarifying the DNA-binding motif ambiguity, MOCCS. Given ChIP-Seq data of any TF, MOCCS comprehensively analyzes and describes every k-mer to which that TF binds. Analysis of simulated datasets revealed that MOCCS is applicable to various ChIP-Seq datasets, requiring only a few minutes per dataset. Application to the ENCODE ChIP-Seq datasets proved that MOCCS directly evaluates whether a given TF binds to each DNA-binding motif, even if known position weight matrix models do not provide sufficient information on DNA-binding motif ambiguity. Furthermore, users are not required to provide numerous parameters or background genomic sequence models that are typically unavailable. MOCCS is implemented in Perl and R and is freely available via https://github.com/yuifu/moccs. By complementing existing motif-discovery software, MOCCS will contribute to the basic understanding of how the genome controls diverse cellular processes via DNA-protein interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    Science.gov (United States)

    Li, Jun; Zhao, Patrick X

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/.

  11. Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

    Directory of Open Access Journals (Sweden)

    Nikhil Sangith

    2014-01-01

    Full Text Available PSMD9 (Proteasome Macropain non-ATPase subunit 9, a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a proteins with conserved C-termini may share common functions and (b PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein, S14 (a ribosomal protein, CSH1 (a growth hormone, E12 (a transcription factor and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions.

  12. Customer Ranking Model for Project Businesses: A Case Study from the Automotive Industry

    Directory of Open Access Journals (Sweden)

    Bernd Markus Zunk

    2014-03-01

    Full Text Available For technology-orientated enterprises that operate project-based businesses, the goal-oriented allocation of scarce marketing resources has great potential to help consolidate their competitive position. An important precondition for goal-oriented management is the identification of the most valuable customers. This enables technology-orientated enterprises to segment markets in order to make tactical marketing decisions. This theorybased paper aims to develop and test a holistic customer ranking model. By deploying the five steps presented in this paper, customer relationship managers are better able to identify and to rank their customers in project-based businesses. A case study provides an example of the application of the method from the automotive industry in Austria. The experiences derived from this case study show that using a customer ranking framework is a crucial factor for enterprises in narrow technology markets to be successful and to achieve their corporate goals.

  13. An Alternative Transcript of the FOG-2 Gene Encodes a FOG-2 Isoform lacking the FOG Repression Motif

    OpenAIRE

    Dale, Rodney M.; Remo, Benjamin F.; Svensson, Eric C.

    2007-01-01

    The FOG family of transcriptional co-factors is composed of two members in mammals: FOG-1 and FOG-2. Both have been shown to bind to GATA factors and function as transcriptional co-repressors in specific cell and promoter contexts. We have previously defined a novel repression domain localized to the N-terminus of each FOG family member, the FOG Repression Motif, which is necessary for FOG-mediated transcriptional repression. In this report, we describe the identification and characterization...

  14. THE MOTIF OF THE SECOND COMING IN RUSSIAN FANTASTIC FICTION

    Directory of Open Access Journals (Sweden)

    Tatyana I. Khoruzhenko

    2017-06-01

    Full Text Available The motif of the Second Coming of Christ takes a special place in Russian fantastic fiction at the turn of the millennium. In the recent decades allusions to the Gospel topic appears in increasing frequency in the genre of fantasy. The aim of the given article was to analyze the peculiarities of the depiction of the subject of Advent in Russian fantastic fiction. As the basis for the research the novels of Y. Voznesenskaya, N. Perumov, V. Khlumov, S. Lukyanenko and T. Ustimenko are of particular interest. The Advent motif appears in the story line of each of the novels in question. Though, the attitude of the authors to the image of the Savior and his second coming to the world fluctuates: from a respectful expectation (Y. Voznesenskaya, T. Ustimenko, S. Lukyanenko to the depiction of the Savior as a monster (N. Perumov. The possibility of an ambivalent interpretation of the Savior is the eloquent evidence of desacralization of this image. The profaning of the sacred is one of the tendencies of the modern popular culture. The genre of fantastic fiction, as a product of mass culture, has caught this trend quite precisely.

  15. Effect of Load Model Using Ranking Identification Technique for Multi Type DG Incorporating Embedded Meta EP-Firefly Algorithm

    Directory of Open Access Journals (Sweden)

    Abdul Rahim Siti Rafidah

    2018-01-01

    Full Text Available This paper presents the effect of load model prior to the distributed generation (DG planning in distribution system. In achieving optimal allocation and placement of DG, a ranking identification technique was proposed in order to study the DG planning using pre-developed Embedded Meta Evolutionary Programming–Firefly Algorithm. The aim of this study is to analyze the effect of different type of DG in order to reduce the total losses considering load factor. To realize the effectiveness of the proposed technique, the IEEE 33 bus test systems was utilized as the test specimen. In this study, the proposed techniques were used to determine the DG sizing and the suitable location for DG planning. The results produced are utilized for the optimization process of DG for the benefit of power system operators and planners in the utility. The power system planner can choose the suitable size and location from the result obtained in this study with the appropriate company’s budget. The modeling of voltage dependent loads has been presented and the results show the voltage dependent load models have a significant effect on total losses of a distribution system for different DG type.

  16. How to Rank Journals.

    Science.gov (United States)

    Bradshaw, Corey J A; Brook, Barry W

    2016-01-01

    There are now many methods available to assess the relative citation performance of peer-reviewed journals. Regardless of their individual faults and advantages, citation-based metrics are used by researchers to maximize the citation potential of their articles, and by employers to rank academic track records. The absolute value of any particular index is arguably meaningless unless compared to other journals, and different metrics result in divergent rankings. To provide a simple yet more objective way to rank journals within and among disciplines, we developed a κ-resampled composite journal rank incorporating five popular citation indices: Impact Factor, Immediacy Index, Source-Normalized Impact Per Paper, SCImago Journal Rank and Google 5-year h-index; this approach provides an index of relative rank uncertainty. We applied the approach to six sample sets of scientific journals from Ecology (n = 100 journals), Medicine (n = 100), Multidisciplinary (n = 50); Ecology + Multidisciplinary (n = 25), Obstetrics & Gynaecology (n = 25) and Marine Biology & Fisheries (n = 25). We then cross-compared the κ-resampled ranking for the Ecology + Multidisciplinary journal set to the results of a survey of 188 publishing ecologists who were asked to rank the same journals, and found a 0.68-0.84 Spearman's ρ correlation between the two rankings datasets. Our composite index approach therefore approximates relative journal reputation, at least for that discipline. Agglomerative and divisive clustering and multi-dimensional scaling techniques applied to the Ecology + Multidisciplinary journal set identified specific clusters of similarly ranked journals, with only Nature & Science separating out from the others. When comparing a selection of journals within or among disciplines, we recommend collecting multiple citation-based metrics for a sample of relevant and realistic journals to calculate the composite rankings and their relative uncertainty windows.

  17. Low-dimensional morphospace of topological motifs in human fMRI brain networks

    Directory of Open Access Journals (Sweden)

    Sarah E. Morgan

    2018-06-01

    Full Text Available We present a low-dimensional morphospace of fMRI brain networks, where axes are defined in a data-driven manner based on the network motifs. The morphospace allows us to identify the key variations in healthy fMRI networks in terms of their underlying motifs, and we observe that two principal components (PCs can account for 97% of the motif variability. The first PC of the motif distribution is correlated with efficiency and inversely correlated with transitivity. Hence this axis approximately conforms to the well-known economical small-world trade-off between integration and segregation in brain networks. Finally, we show that the economical clustering generative model proposed by Vértes et al. (2012 can approximately reproduce the motif morphospace of the real fMRI brain networks, in contrast to other generative models. Overall, the motif morphospace provides a powerful way to visualize the relationships between network properties and to investigate generative or constraining factors in the formation of complex human brain functional networks. Motifs have been described as the building blocks of complex networks. Meanwhile, a morphospace allows networks to be placed in a common space and can reveal the relationships between different network properties and elucidate the driving forces behind network topology. We combine the concepts of motifs and morphospaces to create the first motif morphospace of fMRI brain networks. Crucially, the morphospace axes are defined by the motifs, in a data-driven manner. We observe strong correlations between the networks’ positions in morphospace and their global topological properties, suggesting that motif morphospaces are a powerful way to capture the topology of networks in a low-dimensional space and to compare generative models of brain networks. Motif morphospaces could also be used to study other complex networks’ topologies.

  18. An approach to evaluate the topological significance of motifs and other patterns in regulatory networks

    Directory of Open Access Journals (Sweden)

    Wingender Edgar

    2009-05-01

    Full Text Available Abstract Background The identification of network motifs as statistically over-represented topological patterns has become one of the most promising topics in the analysis of complex networks. The main focus is commonly made on how they operate by means of their internal organization. Yet, their contribution to a network's global architecture is poorly understood. However, this requires switching from the abstract view of a topological pattern to the level of its instances. Here, we show how a recently proposed metric, the pairwise disconnectivity index, can be adapted to survey if and which kind of topological patterns and their instances are most important for sustaining the connectivity within a network. Results The pairwise disconnectivity index of a pattern instance quantifies the dependency of the pairwise connections between vertices in a network on the presence of this pattern instance. Thereby, it particularly considers how the coherence between the unique constituents of a pattern instance relates to the rest of a network. We have applied the method exemplarily to the analysis of 3-vertex topological pattern instances in the transcription networks of a bacteria (E. coli, a unicellular eukaryote (S. cerevisiae and higher eukaryotes (human, mouse, rat. We found that in these networks only very few pattern instances break lots of the pairwise connections between vertices upon the removal of an instance. Among them network motifs do not prevail. Rather, those patterns that are shared by the three networks exhibit a conspicuously enhanced pairwise disconnectivity index. Additionally, these are often located in close vicinity to each other or are even overlapping, since only a small number of genes are repeatedly present in most of them. Moreover, evidence has gathered that the importance of these pattern instances is due to synergistic rather than merely additive effects between their constituents. Conclusion A new method has been proposed

  19. Memetic algorithms for de novo motif-finding in biomedical sequences.

    Science.gov (United States)

    Bi, Chengpeng

    2012-09-01

    The objectives of this study are to design and implement a new memetic algorithm for de novo motif discovery, which is then applied to detect important signals hidden in various biomedical molecular sequences. In this paper, memetic algorithms are developed and tested in de novo motif-finding problems. Several strategies in the algorithm design are employed that are to not only efficiently explore the multiple sequence local alignment space, but also effectively uncover the molecular signals. As a result, there are a number of key features in the implementation of the memetic motif-finding algorithm (MaMotif), including a chromosome replacement operator, a chromosome alteration-aware local search operator, a truncated local search strategy, and a stochastic operation of local search imposed on individual learning. To test the new algorithm, we compare MaMotif with a few of other similar algorithms using simulated and experimental data including genomic DNA, primary microRNA sequences (let-7 family), and transmembrane protein sequences. The new memetic motif-finding algorithm is successfully implemented in C++, and exhaustively tested with various simulated and real biological sequences. In the simulation, it shows that MaMotif is the most time-efficient algorithm compared with others, that is, it runs 2 times faster than the expectation maximization (EM) method and 16 times faster than the genetic algorithm-based EM hybrid. In both simulated and experimental testing, results show that the new algorithm is compared favorably or superior to other algorithms. Notably, MaMotif is able to successfully discover the transcription factors' binding sites in the chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) data, correctly uncover the RNA splicing signals in gene expression, and precisely find the highly conserved helix motif in the transmembrane protein sequences, as well as rightly detect the palindromic segments in the primary micro

  20. Discovering Motifs in Biological Sequences Using the Micron Automata Processor.

    Science.gov (United States)

    Roy, Indranil; Aluru, Srinivas

    2016-01-01

    Finding approximately conserved sequences, called motifs, across multiple DNA or protein sequences is an important problem in computational biology. In this paper, we consider the (l, d) motif search problem of identifying one or more motifs of length l present in at least q of the n given sequences, with each occurrence differing from the motif in at most d substitutions. The problem is known to be NP-complete, and the largest solved instance reported to date is (26,11). We propose a novel algorithm for the (l,d) motif search problem using streaming execution over a large set of non-deterministic finite automata (NFA). This solution is designed to take advantage of the micron automata processor, a new technology close to deployment that can simultaneously execute multiple NFA in parallel. We demonstrate the capability for solving much larger instances of the (l, d) motif search problem using the resources available within a single automata processor board, by estimating run-times for problem instances (39,18) and (40,17). The paper serves as a useful guide to solving problems using this new accelerator technology.

  1. PISMA: A Visual Representation of Motif Distribution in DNA Sequences

    Directory of Open Access Journals (Sweden)

    Rogelio Alcántara-Silva

    2017-03-01

    Full Text Available Background: Because the graphical presentation and analysis of motif distribution can provide insights for experimental hypothesis, PISMA aims at identifying motifs on DNA sequences, counting and showing them graphically. The motif length ranges from 2 to 10 bases, and the DNA sequences range up to 10 kb. The motif distribution is shown as a bar-code–like, as a gene-map–like, and as a transcript scheme. Results: We obtained graphical schemes of the CpG site distribution from 91 human papillomavirus genomes. Also, we present 2 analyses: one of DNA motifs associated with either methylation-resistant or methylation-sensitive CpG islands and another analysis of motifs associated with exosome RNA secretion. Availability and Implementation: PISMA is developed in Java; it is executable in any type of hardware and in diverse operating systems. PISMA is freely available to noncommercial users. The English version and the User Manual are provided in Supplementary Files 1 and 2, and a Spanish version is available at www.biomedicas.unam.mx/wp-content/software/pisma.zip and www.biomedicas.unam.mx/wp-content/pdf/manual/pisma.pdf .

  2. Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network

    Directory of Open Access Journals (Sweden)

    Barabási Albert-László

    2004-01-01

    Full Text Available Abstract Background Transcriptional regulation of cellular functions is carried out through a complex network of interactions among transcription factors and the promoter regions of genes and operons regulated by them.To better understand the system-level function of such networks simplification of their architecture was previously achieved by identifying the motifs present in the network, which are small, overrepresented, topologically distinct regulatory interaction patterns (subgraphs. However, the interaction of such motifs with each other, and their form of integration into the full network has not been previously examined. Results By studying the transcriptional regulatory network of the bacterium, Escherichia coli, we demonstrate that the two previously identified motif types in the network (i.e., feed-forward loops and bi-fan motifs do not exist in isolation, but rather aggregate into homologous motif clusters that largely overlap with known biological functions. Moreover, these clusters further coalesce into a supercluster, thus establishing distinct topological hierarchies that show global statistical properties similar to the whole network. Targeted removal of motif links disintegrates the network into small, isolated clusters, while random disruptions of equal number of links do not cause such an effect. Conclusion Individual motifs aggregate into homologous motif clusters and a supercluster forming the backbone of the E. coli transcriptional regulatory network and play a central role in defining its global topological organization.

  3. A common minimal motif for the ligands of HLA-B*27 class I molecules.

    Science.gov (United States)

    Barriga, Alejandro; Lorente, Elena; Johnstone, Carolina; Mir, Carmen; del Val, Margarita; López, Daniel

    2014-01-01

    CD8(+) T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA) class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

  4. A common minimal motif for the ligands of HLA-B*27 class I molecules.

    Directory of Open Access Journals (Sweden)

    Alejandro Barriga

    Full Text Available CD8(+ T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

  5. Parallel motif extraction from very long sequences

    KAUST Repository

    Sahli, Majed

    2013-01-01

    Motifs are frequent patterns used to identify biological functionality in genomic sequences, periodicity in time series, or user trends in web logs. In contrast to a lot of existing work that focuses on collections of many short sequences, modern applications require mining of motifs in one very long sequence (i.e., in the order of several gigabytes). For this case, there exist statistical approaches that are fast but inaccurate; or combinatorial methods that are sound and complete. Unfortunately, existing combinatorial methods are serial and very slow. Consequently, they are limited to very short sequences (i.e., a few megabytes), small alphabets (typically 4 symbols for DNA sequences), and restricted types of motifs. This paper presents ACME, a combinatorial method for extracting motifs from a single very long sequence. ACME arranges the search space in contiguous blocks that take advantage of the cache hierarchy in modern architectures, and achieves almost an order of magnitude performance gain in serial execution. It also decomposes the search space in a smart way that allows scalability to thousands of processors with more than 90% speedup. ACME is the only method that: (i) scales to gigabyte-long sequences; (ii) handles large alphabets; (iii) supports interesting types of motifs with minimal additional cost; and (iv) is optimized for a variety of architectures such as multi-core systems, clusters in the cloud, and supercomputers. ACME reduces the extraction time for an exact-length query from 4 hours to 7 minutes on a typical workstation; handles 3 orders of magnitude longer sequences; and scales up to 16, 384 cores on a supercomputer. Copyright is held by the owner/author(s).

  6. The Homogeneity of Social Selection in Accessing Higher Ranked Universities

    DEFF Research Database (Denmark)

    Munk, Martin David; Baklanov, Nikita

    2018-01-01

    This paper demonstrates the persistence of social selectivity throughout the educational ladder, with evident social reproduction at the top. By jointly modelling multiple choices of high school, university, field of study, and institutional rank of university using a multinomial transition model...

  7. MODA: an efficient algorithm for network motif discovery in biological networks.

    Science.gov (United States)

    Omidi, Saeed; Schreiber, Falk; Masoudi-Nejad, Ali

    2009-10-01

    In recent years, interest has been growing in the study of complex networks. Since Erdös and Rényi (1960) proposed their random graph model about 50 years ago, many researchers have investigated and shaped this field. Many indicators have been proposed to assess the global features of networks. Recently, an active research area has developed in studying local features named motifs as the building blocks of networks. Unfortunately, network motif discovery is a computationally hard problem and finding rather large motifs (larger than 8 nodes) by means of current algorithms is impractical as it demands too much computational effort. In this paper, we present a new algorithm (MODA) that incorporates techniques such as a pattern growth approach for extracting larger motifs efficiently. We have tested our algorithm and found it able to identify larger motifs with more than 8 nodes more efficiently than most of the current state-of-the-art motif discovery algorithms. While most of the algorithms rely on induced subgraphs as motifs of the networks, MODA is able to extract both induced and non-induced subgraphs simultaneously. The MODA source code is freely available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

  8. A method for integrating and ranking the evidence for biochemical pathways by mining reactions from text

    Science.gov (United States)

    Miwa, Makoto; Ohta, Tomoko; Rak, Rafal; Rowley, Andrew; Kell, Douglas B.; Pyysalo, Sampo; Ananiadou, Sophia

    2013-01-01

    Motivation: To create, verify and maintain pathway models, curators must discover and assess knowledge distributed over the vast body of biological literature. Methods supporting these tasks must understand both the pathway model representations and the natural language in the literature. These methods should identify and order documents by relevance to any given pathway reaction. No existing system has addressed all aspects of this challenge. Method: We present novel methods for associating pathway model reactions with relevant publications. Our approach extracts the reactions directly from the models and then turns them into queries for three text mining-based MEDLINE literature search systems. These queries are executed, and the resulting documents are combined and ranked according to their relevance to the reactions of interest. We manually annotate document-reaction pairs with the relevance of the document to the reaction and use this annotation to study several ranking methods, using various heuristic and machine-learning approaches. Results: Our evaluation shows that the annotated document-reaction pairs can be used to create a rule-based document ranking system, and that machine learning can be used to rank documents by their relevance to pathway reactions. We find that a Support Vector Machine-based system outperforms several baselines and matches the performance of the rule-based system. The success of the query extraction and ranking methods are used to update our existing pathway search system, PathText. Availability: An online demonstration of PathText 2 and the annotated corpus are available for research purposes at http://www.nactem.ac.uk/pathtext2/. Contact: makoto.miwa@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23813008

  9. Evaluation of the osteoclastogenic process associated with RANK / RANK-L / OPG in odontogenic myxomas

    Science.gov (United States)

    González-Galván, María del Carmen; Mosqueda-Taylor, Adalberto; Bologna-Molina, Ronell; Setien-Olarra, Amaia; Marichalar-Mendia, Xabier; Aguirre-Urizar, José-Manuel

    2018-01-01

    Background Odontogenic myxoma (OM) is a benign intraosseous neoplasm that exhibits local aggressiveness and high recurrence rates. Osteoclastogenesis is an important phenomenon in the tumor growth of maxillary neoplasms. RANK (Receptor Activator of Nuclear Factor κappa B) is the signaling receptor of RANK-L (Receptor activator of nuclear factor kappa-Β ligand) that activates the osteoclasts. OPG (osteoprotegerin) is a decoy receptor for RANK-L that inhibits pro-osteoclastogenesis. The RANK / RANKL / OPG system participates in the regulation of osteolytic activity under normal conditions, and its alteration has been associated with greater bone destruction, and also with tumor growth. Objectives To analyze the immunohistochemical expression of OPG, RANK and RANK-L proteins in odontogenic myxomas (OMs) and their relationship with the tumor size. Material and Methods Eighteen OMs, 4 small ( 3cm) and 18 dental follicles (DF) that were included as control were studied by means of standard immunohistochemical procedure with RANK, RANKL and OPG antibodies. For the evaluation, 5 fields (40x) of representative areas of OM and DF were selected where the expression of each antibody was determined. Descriptive and comparative statistical analyses were performed with the obtained data. Results There are significant differences in the expression of RANK in OM samples as compared to DF (p = 0.022) and among the OMSs and OMLs (p = 0.032). Also a strong association is recognized in the expression of RANK-L and OPG in OM samples. Conclusions Activation of the RANK / RANK-L / OPG triad seems to be involved in the mechanisms of bone balance and destruction, as well as associated with tumor growth in odontogenic myxomas. Key words:Odontogenic myxoma, dental follicle, RANK, RANK-L, OPG, osteoclastogenesis. PMID:29680857

  10. Sparse structure regularized ranking

    KAUST Repository

    Wang, Jim Jing-Yan; Sun, Yijun; Gao, Xin

    2014-01-01

    Learning ranking scores is critical for the multimedia database retrieval problem. In this paper, we propose a novel ranking score learning algorithm by exploring the sparse structure and using it to regularize ranking scores. To explore the sparse

  11. Dynamic motifs in socio-economic networks

    Science.gov (United States)

    Zhang, Xin; Shao, Shuai; Stanley, H. Eugene; Havlin, Shlomo

    2014-12-01

    Socio-economic networks are of central importance in economic life. We develop a method of identifying and studying motifs in socio-economic networks by focusing on “dynamic motifs,” i.e., evolutionary connection patterns that, because of “node acquaintances” in the network, occur much more frequently than random patterns. We examine two evolving bi-partite networks: i) the world-wide commercial ship chartering market and ii) the ship build-to-order market. We find similar dynamic motifs in both bipartite networks, even though they describe different economic activities. We also find that “influence” and “persistence” are strong factors in the interaction behavior of organizations. When two companies are doing business with the same customer, it is highly probable that another customer who currently only has business relationship with one of these two companies, will become customer of the second in the future. This is the effect of influence. Persistence means that companies with close business ties to customers tend to maintain their relationships over a long period of time.

  12. A Ranking Analysis of the Management Schools in Greater China (2000-2010): Evidence from the SSCI Database

    Science.gov (United States)

    Hou, Mingjun; Fan, Peihua; Liu, Heng

    2014-01-01

    The authors rank the management schools in Greater China (including Mainland China, Hong Kong, Taiwan, and Macau) based on their academic publications in the Social Sciences Citation Index management and business journals from 2000 to 2010. Following K. Ritzberger's (2008) and X. Yu and Z. Gao's (2010) ranking method, the authors develop six…

  13. Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

    Science.gov (United States)

    Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.

    2015-01-01

    Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906

  14. Grooming up the hierarchy: the exchange of grooming and rank-related benefits in a new world primate.

    Directory of Open Access Journals (Sweden)

    Barbara Tiddi

    Full Text Available Seyfarth's model assumes that female primates derive rank-related benefits from higher-ranking females in exchange for grooming. As a consequence, the model predicts females prefer high-ranking females as grooming partners and compete for the opportunity to groom them. Therefore, allogrooming is expected to be directed up the dominance hierarchy and to occur more often between females with adjacent ranks. Although data from Old World primates generally support the model, studies on the relation between grooming and dominance rank in the New World genus Cebus have found conflicting results, showing considerable variability across groups and species. In this study, we investigated the pattern of grooming in wild tufted capuchin females (Cebus apella nigritus in Iguazú National Park, Argentina by testing both the assumption (i.e., that females gain rank-related return benefits from grooming and predictions (i.e., that females direct grooming up the dominance hierarchy and the majority of grooming occurs between females with adjacent ranks of Seyfarth's model. Study subjects were 9 adult females belonging to a single group. Results showed that grooming was given in return for tolerance during naturally occurring feeding, a benefit that higher-ranking females can more easily grant. Female grooming was directed up the hierarchy and was given more often to partners with similar rank. These findings provide supporting evidence for both the assumption and predictions of Seyfarth's model and represent, more generally, the first evidence of reciprocal behavioural interchanges driven by rank-related benefits in New World female primates.

  15. Grooming up the hierarchy: the exchange of grooming and rank-related benefits in a new world primate.

    Science.gov (United States)

    Tiddi, Barbara; Aureli, Filippo; Schino, Gabriele

    2012-01-01

    Seyfarth's model assumes that female primates derive rank-related benefits from higher-ranking females in exchange for grooming. As a consequence, the model predicts females prefer high-ranking females as grooming partners and compete for the opportunity to groom them. Therefore, allogrooming is expected to be directed up the dominance hierarchy and to occur more often between females with adjacent ranks. Although data from Old World primates generally support the model, studies on the relation between grooming and dominance rank in the New World genus Cebus have found conflicting results, showing considerable variability across groups and species. In this study, we investigated the pattern of grooming in wild tufted capuchin females (Cebus apella nigritus) in Iguazú National Park, Argentina by testing both the assumption (i.e., that females gain rank-related return benefits from grooming) and predictions (i.e., that females direct grooming up the dominance hierarchy and the majority of grooming occurs between females with adjacent ranks) of Seyfarth's model. Study subjects were 9 adult females belonging to a single group. Results showed that grooming was given in return for tolerance during naturally occurring feeding, a benefit that higher-ranking females can more easily grant. Female grooming was directed up the hierarchy and was given more often to partners with similar rank. These findings provide supporting evidence for both the assumption and predictions of Seyfarth's model and represent, more generally, the first evidence of reciprocal behavioural interchanges driven by rank-related benefits in New World female primates.

  16. Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

    Science.gov (United States)

    Kinjo, Akira R.; Nakamura, Haruki

    2012-01-01

    Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

  17. Identification of a tripartite import signal in the Ewing Sarcoma protein (EWS)

    International Nuclear Information System (INIS)

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G.; Eggleton, Paul; Lorson, Christian L.; Young, Philip J.

    2009-01-01

    The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.

  18. Identification of a tripartite import signal in the Ewing Sarcoma protein (EWS)

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G. [Clinical Neurobiology, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom); Eggleton, Paul [Inflammation and Musculoskeletal Disease, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom); MRC Immunochemistry Unit, University of Oxford, Oxford OX1 3QU (United Kingdom); Lorson, Christian L. [Department of Veterinary Pathobiology, Bond Life Sciences Center, 1201 Rollins Road, University of Missouri, Columbia, MO 65211 (United States); Young, Philip J., E-mail: philip.young@pms.ac.uk [Clinical Neurobiology, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom)

    2009-12-25

    The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.

  19. Probing structural changes of self assembled i-motif DNA

    KAUST Repository

    Lee, Iljoon; Patil, Sachin; Fhayli, Karim; Alsaiari, Shahad K.; Khashab, Niveen M.

    2015-01-01

    We report an i-motif structural probing system based on Thioflavin T (ThT) as a fluorescent sensor. This probe can discriminate the structural changes of RET and Rb i-motif sequences according to pH change. This journal is

  20. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

    Directory of Open Access Journals (Sweden)

    Down Thomas A

    2010-09-01

    Full Text Available Abstract Background DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS" but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq not to be biological transcription factor binding sites ("empirical TFBS". We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Results Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Conclusions Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation.

  1. Time evolution of Wikipedia network ranking

    Science.gov (United States)

    Eom, Young-Ho; Frahm, Klaus M.; Benczúr, András; Shepelyansky, Dima L.

    2013-12-01

    We study the time evolution of ranking and spectral properties of the Google matrix of English Wikipedia hyperlink network during years 2003-2011. The statistical properties of ranking of Wikipedia articles via PageRank and CheiRank probabilities, as well as the matrix spectrum, are shown to be stabilized for 2007-2011. A special emphasis is done on ranking of Wikipedia personalities and universities. We show that PageRank selection is dominated by politicians while 2DRank, which combines PageRank and CheiRank, gives more accent on personalities of arts. The Wikipedia PageRank of universities recovers 80% of top universities of Shanghai ranking during the considered time period.

  2. BlockLogo: Visualization of peptide and sequence motif conservation

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian

    2013-01-01

    BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, se...

  3. Forensic evidence collection and DNA identification in acute child sexual assault.

    Science.gov (United States)

    Thackeray, Jonathan D; Hornor, Gail; Benzinger, Elizabeth A; Scribano, Philip V

    2011-08-01

    To describe forensic evidence findings and reevaluate previous recommendations with respect to timing of evidence collection in acute child sexual assault and to identify factors associated with yield of DNA. This was a retrospective review of medical and legal records of patients aged 0 to 20 years who required forensic evidence collection. Ninety-seven of 388 (25%) processed evidence-collection kits were positive and 63 (65%) of them produced identifiable DNA. There were 20 positive samples obtained from children younger than 10 years; 17 of these samples were obtained from children seen within 24 hours of the assault. Three children had positive body samples beyond 24 hours after the assault, including 1 child positive for salivary amylase in the underwear and on the thighs 54 hours after the assault. DNA was found in 11 children aged younger than 10 years, including the child seen 54 hours after the assault. Collection of evidence within 24 hours of the assault was identified as an independent predictor of DNA detection. Identifiable DNA was collected from a child's body despite cases in which: evidence collection was performed >24 hours beyond the assault; the child had a normal/nonacute anogenital examination; there was no reported history of ejaculation; and the victim had bathed and/or changed clothes before evidence collection. Failure to conduct evidence collection on prepubertal children beyond 24 hours after the assault will result in rare missed opportunities to identify forensic evidence, including identification of DNA.

  4. Multiple graph regularized protein domain ranking.

    Science.gov (United States)

    Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin

    2012-11-19

    Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.

  5. Genome Analysis of Conserved Dehydrin Motifs in Vascular Plants

    Directory of Open Access Journals (Sweden)

    Ahmad A. Malik

    2017-05-01

    Full Text Available Dehydrins, a large family of abiotic stress proteins, are defined by the presence of a mostly conserved motif known as the K-segment, and may also contain two other conserved motifs known as the Y-segment and S-segment. Using the dehydrin literature, we developed a sequence motif definition of the K-segment, which we used to create a large dataset of dehydrin sequences by searching the Pfam00257 dehydrin dataset and the Phytozome 10 sequences of vascular plants. A comprehensive analysis of these sequences reveals that lysine residues are highly conserved in the K-segment, while the amino acid type is often conserved at other positions. Despite the Y-segment name, the central tyrosine is somewhat conserved, but can be substituted with two other small aromatic amino acids (phenylalanine or histidine. The S-segment contains a series of serine residues, but in some proteins is also preceded by a conserved LHR sequence. In many dehydrins containing all three of these motifs the S-segment is linked to the K-segment by a GXGGRRKK motif (where X can be any amino acid, suggesting a functional linkage between these two motifs. An analysis of the sequences shows that the dehydrin architecture and several biochemical properties (isoelectric point, molecular mass, and hydrophobicity score are dependent on each other, and that some dehydrin architectures are overexpressed during certain abiotic stress, suggesting that they may be optimized for a specific abiotic stress while others are involved in all forms of dehydration stress (drought, cold, and salinity.

  6. RegRNA: an integrated web server for identifying regulatory RNA motifs and elements

    OpenAIRE

    Huang, Hsi-Yuan; Chien, Chia-Hung; Jen, Kuan-Hua; Huang, Hsien-Da

    2006-01-01

    Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5′-untra...

  7. Strategic Entrepreneurship Based Model of Catch-up University in Global Rankings

    Directory of Open Access Journals (Sweden)

    Kozlov Mikhail

    2016-01-01

    Full Text Available The paper will help answer the question, why only few universities managed to succeed significantly in their global ranking advancement, while most of their competitors fail. For this purpose it will introduce a new strategically entrepreneurial catch-up university framework, based on the combination of the resource based view, dynamic capabilities, strategic entrepreneurship and latecomer organization concepts. The new framework logics explains the advantages of being ambidextrous for ranking oriented universities and pursuing new potentially more favorable opportunities for research development. It will propose that substantial increase in the level of dynamic capabilities of the universities and their resource base accumulation is based on the use of the new combination of financial, human and social capital combined with strategic management of these resources in the process of identification and exploitation of greater opportunities.

  8. Next Generation Nuclear Plant Phenomena Identification and Ranking Tables (PIRTs) Volume 4: High-Temperature Materials PIRTs

    Energy Technology Data Exchange (ETDEWEB)

    Corwin, William R [ORNL; Ballinger, R. [Massachusetts Institute of Technology (MIT); Majumdar, S. [Argonne National Laboratory (ANL); Weaver, K. D. [Idaho National Laboratory (INL)

    2008-03-01

    The Phenomena Identification and Ranking Table (PIRT) technique was used to identify safety-relevant/safety-significant phenomena and assess the importance and related knowledge base of high-temperature structural materials issues for the Next Generation Nuclear Plant (NGNP), a very high temperature gas-cooled reactor (VHTR). The major aspects of materials degradation phenomena that may give rise to regulatory safety concern for the NGNP were evaluated for major structural components and the materials comprising them, including metallic and nonmetallic materials for control rods, other reactor internals, and primary circuit components; metallic alloys for very high-temperature service for heat exchangers and turbomachinery, metallic alloys for high-temperature service for the reactor pressure vessel (RPV), other pressure vessels and components in the primary and secondary circuits; and metallic alloys for secondary heat transfer circuits and the balance of plant. These materials phenomena were primarily evaluated with regard to their potential for contributing to fission product release at the site boundary under a variety of event scenarios covering normal operation, anticipated transients, and accidents. Of all the high-temperature metallic components, the one most likely to be heavily challenged in the NGNP will be the intermediate heat exchanger (IHX). Its thin, internal sections must be able to withstand the stresses associated with thermal loading and pressure drops between the primary and secondary loops under the environments and temperatures of interest. Several important materials-related phenomena related to the IHX were identified, including crack initiation and propagation; the lack of experience of primary boundary design methodology limitations for new IHX structures; and manufacturing phenomena for new designs. Specific issues were also identified for RPVs that will likely be too large for shop fabrication and transportation. Validated procedures

  9. Multiplex PageRank.

    Directory of Open Access Journals (Sweden)

    Arda Halu

    Full Text Available Many complex systems can be described as multiplex networks in which the same nodes can interact with one another in different layers, thus forming a set of interacting and co-evolving networks. Examples of such multiplex systems are social networks where people are involved in different types of relationships and interact through various forms of communication media. The ranking of nodes in multiplex networks is one of the most pressing and challenging tasks that research on complex networks is currently facing. When pairs of nodes can be connected through multiple links and in multiple layers, the ranking of nodes should necessarily reflect the importance of nodes in one layer as well as their importance in other interdependent layers. In this paper, we draw on the idea of biased random walks to define the Multiplex PageRank centrality measure in which the effects of the interplay between networks on the centrality of nodes are directly taken into account. In particular, depending on the intensity of the interaction between layers, we define the Additive, Multiplicative, Combined, and Neutral versions of Multiplex PageRank, and show how each version reflects the extent to which the importance of a node in one layer affects the importance the node can gain in another layer. We discuss these measures and apply them to an online multiplex social network. Findings indicate that taking the multiplex nature of the network into account helps uncover the emergence of rankings of nodes that differ from the rankings obtained from one single layer. Results provide support in favor of the salience of multiplex centrality measures, like Multiplex PageRank, for assessing the prominence of nodes embedded in multiple interacting networks, and for shedding a new light on structural properties that would otherwise remain undetected if each of the interacting networks were analyzed in isolation.

  10. Multiplex PageRank.

    Science.gov (United States)

    Halu, Arda; Mondragón, Raúl J; Panzarasa, Pietro; Bianconi, Ginestra

    2013-01-01

    Many complex systems can be described as multiplex networks in which the same nodes can interact with one another in different layers, thus forming a set of interacting and co-evolving networks. Examples of such multiplex systems are social networks where people are involved in different types of relationships and interact through various forms of communication media. The ranking of nodes in multiplex networks is one of the most pressing and challenging tasks that research on complex networks is currently facing. When pairs of nodes can be connected through multiple links and in multiple layers, the ranking of nodes should necessarily reflect the importance of nodes in one layer as well as their importance in other interdependent layers. In this paper, we draw on the idea of biased random walks to define the Multiplex PageRank centrality measure in which the effects of the interplay between networks on the centrality of nodes are directly taken into account. In particular, depending on the intensity of the interaction between layers, we define the Additive, Multiplicative, Combined, and Neutral versions of Multiplex PageRank, and show how each version reflects the extent to which the importance of a node in one layer affects the importance the node can gain in another layer. We discuss these measures and apply them to an online multiplex social network. Findings indicate that taking the multiplex nature of the network into account helps uncover the emergence of rankings of nodes that differ from the rankings obtained from one single layer. Results provide support in favor of the salience of multiplex centrality measures, like Multiplex PageRank, for assessing the prominence of nodes embedded in multiple interacting networks, and for shedding a new light on structural properties that would otherwise remain undetected if each of the interacting networks were analyzed in isolation.

  11. Multiple graph regularized protein domain ranking

    KAUST Repository

    Wang, Jim Jing-Yan

    2012-11-19

    Background: Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods.Results: To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods.Conclusion: The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. 2012 Wang et al; licensee BioMed Central Ltd.

  12. Multiple graph regularized protein domain ranking

    KAUST Repository

    Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin

    2012-01-01

    Background: Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods.Results: To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods.Conclusion: The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. 2012 Wang et al; licensee BioMed Central Ltd.

  13. Multiple graph regularized protein domain ranking

    Directory of Open Access Journals (Sweden)

    Wang Jim

    2012-11-01

    Full Text Available Abstract Background Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. Results To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. Conclusion The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.

  14. Sex-reversed correlation between stress levels and dominance rank in a captive non-breeder flock of crows.

    Science.gov (United States)

    Ode, Minami; Asaba, Akari; Miyazawa, Eri; Mogi, Kazutaka; Kikusui, Takefumi; Izawa, Ei-Ichi

    2015-07-01

    Group living has both benefits and costs to individuals; benefits include efficient acquisition of resources, and costs include stress from social conflicts among group members. Such social challenges result in hierarchical dominance ranking among group members as a solution to avoid escalating conflict that causes different levels of basal stress between individuals at different ranks. Stress-associated glucocorticoid (corticosterone in rodents and birds; CORT) levels are known to correlate with dominance rank in diverse taxa and to covary with various social factors, such as sex and dominance maintenance styles. Although there is much evidence for sex differences in the basal levels of CORT in various species, the correlation of sex differences in basal CORT with dominance rank is poorly understood. We investigated the correlation between CORT metabolites (CM) in the droppings and social factors, including rank and sex, in a captive non-breeder group of crows. In this group, all the single males dominated all the single females, and dominance ranks were stable among single males but relatively unstable among single females. CM levels and rank were significantly correlated in a sex-reversed fashion: males at higher rank (i.e., more dominant) had higher CM, whereas females at higher rank exhibited lower CM. This is the first evidence of sex-reversed patterns of CM-rank correlation in birds. The results suggest that different mechanisms of stress-dominance relationships operate on the sexes in non-breeder crow aggregations; in males, stress is associated with the cost of aggressive displays, whereas females experience subordination stress due to males' overt aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Evidence-based practice for pain identification in cognitively impaired nursing home residents.

    Science.gov (United States)

    Sacoco, Christina; Ishikawa, Sally

    2014-09-01

    Pain identification of cognitively impaired elderly is very challenging. This project aimed to identify best practices for pain assessment in nursing home residents with cognitive impairment and to establish a standardized pain assessment guide to optimize nursing practice and resident outcomes. The Iowa Model of Evidence-Based Practice to Promote Quality of Care guided the project's process. Phase I of the project analyzed data gained from chart reviews on current practices of pain assessment, and Phase II used the results of Phase I to develop, implement, and evaluate an evidence-based practice standard for nursing assessment of pain for cognitively impaired residents. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Improving Ranking Using Quantum Probability

    OpenAIRE

    Melucci, Massimo

    2011-01-01

    The paper shows that ranking information units by quantum probability differs from ranking them by classical probability provided the same data used for parameter estimation. As probability of detection (also known as recall or power) and probability of false alarm (also known as fallout or size) measure the quality of ranking, we point out and show that ranking by quantum probability yields higher probability of detection than ranking by classical probability provided a given probability of ...

  17. RNA recognition motif (RRM)-containing proteins in Bombyx mori

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Recognition Motif (RRM), sometimes referred to as. RNP1, is one of the first identified domains for RNA interaction. RRM is very common ..... Apart from the RRM motif, eIF3-S9 has a Trp-Asp. (WD) repeat domain, Poly (A) ...

  18. Biomimetic trapping cocktail to screen reactive metabolites: use of an amino acid and DNA motif mixture as light/heavy isotope pairs differing in mass shift.

    Science.gov (United States)

    Hosaka, Shuto; Honda, Takuto; Lee, Seon Hwa; Oe, Tomoyuki

    2018-06-01

    Candidate drugs that can be metabolically transformed into reactive electrophilic products, such as epoxides, quinones, and nitroso compounds, are of special concern because subsequent covalent binding to bio-macromolecules can cause adverse drug reactions, such as allergic reactions, hepatotoxicity, and genotoxicity. Several strategies have been reported for screening reactive metabolites, such as a covalent binding assay with radioisotope-labeled drugs and a trapping method followed by LC-MS/MS analyses. Of these, a trapping method using glutathione is the most common, especially at the early stage of drug development. However, the cysteine of glutathione is not the only nucleophilic site in vivo; lysine, histidine, arginine, and DNA bases are also nucleophilic. Indeed, the glutathione trapping method tends to overlook several types of reactive metabolites, such as aldehydes, acylglucuronides, and nitroso compounds. Here, we introduce an alternate way for screening reactive metabolites as follows: A mixture of the light and heavy isotopes of simplified amino acid motifs and a DNA motif is used as a biomimetic trapping cocktail. This mixture consists of [ 2 H 0 ]/[ 2 H 3 ]-1-methylguanidine (arginine motif, Δ 3 Da), [ 2 H 0 ]/[ 2 H 4 ]-2-mercaptoethanol (cysteine motif, Δ 4 Da), [ 2 H 0 ]/[ 2 H 5 ]-4-methylimidazole (histidine motif, Δ 5 Da), [ 2 H 0 ]/[ 2 H 9 ]-n-butylamine (lysine motif, Δ 9 Da), and [ 13 C 0 , 15 N 0 ]/[ 13 C 1 , 15 N 2 ]-2'-deoxyguanosine (DNA motif, Δ 3 Da). Mass tag triggered data-dependent acquisition is used to find the characteristic doublet peaks, followed by specific identification of the light isotope peak using MS/MS. Forty-two model drugs were examined using an in vitro microsome experiment to validate the strategy. Graphical abstract Biomimetic trapping cocktail to screen reactive metabolites.

  19. Bounded search for de novo identification of degenerate cis-regulatory elements

    Directory of Open Access Journals (Sweden)

    Khetani Radhika S

    2006-05-01

    Full Text Available Abstract Background The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach. Results In this paper, we report PRISM, a degenerate motif finder that leverages the relationship between the statistical significance of a set of binding sites and that of the individual binding sites. PRISM first identifies overrepresented, non-degenerate consensus motifs, then iteratively relaxes each one into a high-scoring degenerate motif. This approach requires no tunable parameters, thereby lending itself to unbiased performance comparisons. We therefore compare PRISM's performance against nine popular motif finders on 28 well-characterized S. cerevisiae regulons. PRISM consistently outperforms all other programs. Finally, we use PRISM to predict the binding sites of uncharacterized regulons. Our results support a proposed mechanism of action for the yeast cell-cycle transcription factor Stb1, whose binding site has not been determined experimentally. Conclusion The relationship between statistical measures of the binding sites and the set as a whole leads to a simple means of identifying the diverse range of cis-regulatory elements to which a protein binds. This approach leverages the advantages of word-counting, in that position dependencies are implicitly accounted for and local optima are more easily avoided. While we sacrifice guaranteed optimality to prevent the exponential blowup of exhaustive search, we prove that the error

  20. How Many Alternatives Can Be Ranked? A Comparison of the Paired Comparison and Ranking Methods.

    Science.gov (United States)

    Ock, Minsu; Yi, Nari; Ahn, Jeonghoon; Jo, Min-Woo

    2016-01-01

    To determine the feasibility of converting ranking data into paired comparison (PC) data and suggest the number of alternatives that can be ranked by comparing a PC and a ranking method. Using a total of 222 health states, a household survey was conducted in a sample of 300 individuals from the general population. Each respondent performed a PC 15 times and a ranking method 6 times (two attempts of ranking three, four, and five health states, respectively). The health states of the PC and the ranking method were constructed to overlap each other. We converted the ranked data into PC data and examined the consistency of the response rate. Applying probit regression, we obtained the predicted probability of each method. Pearson correlation coefficients were determined between the predicted probabilities of those methods. The mean absolute error was also assessed between the observed and the predicted values. The overall consistency of the response rate was 82.8%. The Pearson correlation coefficients were 0.789, 0.852, and 0.893 for ranking three, four, and five health states, respectively. The lowest mean absolute error was 0.082 (95% confidence interval [CI] 0.074-0.090) in ranking five health states, followed by 0.123 (95% CI 0.111-0.135) in ranking four health states and 0.126 (95% CI 0.113-0.138) in ranking three health states. After empirically examining the consistency of the response rate between a PC and a ranking method, we suggest that using five alternatives in the ranking method may be superior to using three or four alternatives. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. Neophilia Ranking of Scientific Journals.

    Science.gov (United States)

    Packalen, Mikko; Bhattacharya, Jay

    2017-01-01

    The ranking of scientific journals is important because of the signal it sends to scientists about what is considered most vital for scientific progress. Existing ranking systems focus on measuring the influence of a scientific paper (citations)-these rankings do not reward journals for publishing innovative work that builds on new ideas. We propose an alternative ranking based on the proclivity of journals to publish papers that build on new ideas, and we implement this ranking via a text-based analysis of all published biomedical papers dating back to 1946. In addition, we compare our neophilia ranking to citation-based (impact factor) rankings; this comparison shows that the two ranking approaches are distinct. Prior theoretical work suggests an active role for our neophilia index in science policy. Absent an explicit incentive to pursue novel science, scientists underinvest in innovative work because of a coordination problem: for work on a new idea to flourish, many scientists must decide to adopt it in their work. Rankings that are based purely on influence thus do not provide sufficient incentives for publishing innovative work. By contrast, adoption of the neophilia index as part of journal-ranking procedures by funding agencies and university administrators would provide an explicit incentive for journals to publish innovative work and thus help solve the coordination problem by increasing scientists' incentives to pursue innovative work.

  2. One motif to bind them: A small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs.

    Science.gov (United States)

    Lock, Antonia; Forfar, Rachel; Weston, Cathryn; Bowsher, Leo; Upton, Graham J G; Reynolds, Christopher A; Ladds, Graham; Dixon, Ann M

    2014-12-01

    G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs. Copyright © 2014. Published by Elsevier B.V.

  3. Hierarchical partial order ranking

    International Nuclear Information System (INIS)

    Carlsen, Lars

    2008-01-01

    Assessing the potential impact on environmental and human health from the production and use of chemicals or from polluted sites involves a multi-criteria evaluation scheme. A priori several parameters are to address, e.g., production tonnage, specific release scenarios, geographical and site-specific factors in addition to various substance dependent parameters. Further socio-economic factors may be taken into consideration. The number of parameters to be included may well appear to be prohibitive for developing a sensible model. The study introduces hierarchical partial order ranking (HPOR) that remedies this problem. By HPOR the original parameters are initially grouped based on their mutual connection and a set of meta-descriptors is derived representing the ranking corresponding to the single groups of descriptors, respectively. A second partial order ranking is carried out based on the meta-descriptors, the final ranking being disclosed though average ranks. An illustrative example on the prioritisation of polluted sites is given. - Hierarchical partial order ranking of polluted sites has been developed for prioritization based on a large number of parameters

  4. Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1.

    Science.gov (United States)

    Lasalde, Clarivel; Rivera, Andrea V; León, Alfredo J; González-Feliciano, José A; Estrella, Luis A; Rodríguez-Cruz, Eva N; Correa, María E; Cajigas, Iván J; Bracho, Dina P; Vega, Irving E; Wilkinson, Miles F; González, Carlos I

    2014-02-01

    One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.

  5. Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif

    Directory of Open Access Journals (Sweden)

    Launey Thomas

    2011-06-01

    Full Text Available Abstract Background The interactions between PDZ (PSD-95, Dlg, ZO-1 domains and PDZ-binding motifs play central roles in signal transductions within cells. Proteins with PDZ domains bind to PDZ-binding motifs almost exclusively when the motifs are located at the carboxyl (C- terminal ends of their binding partners. However, it remains little explored whether PDZ-binding motifs show any preferential location at the C-terminal ends of proteins, at genome-level. Results Here, we examined the distribution of the type-I (x-x-S/T-x-I/L/V or type-II (x-x-V-x-I/V PDZ-binding motifs in proteins encoded in the genomes of five different species (human, mouse, zebrafish, fruit fly and nematode. We first established that these PDZ-binding motifs are indeed preferentially present at their C-terminal ends. Moreover, we found specific amino acid (AA bias for the 'x' positions in the motifs at the C-terminal ends. In general, hydrophilic AAs were favored. Our genomics-based findings confirm and largely extend the results of previous interaction-based studies, allowing us to propose refined consensus sequences for all of the examined PDZ-binding motifs. An ontological analysis revealed that the refined motifs are functionally relevant since a large fraction of the proteins bearing the motif appear to be involved in signal transduction. Furthermore, co-precipitation experiments confirmed two new protein interactions predicted by our genomics-based approach. Finally, we show that influenza virus pathogenicity can be correlated with PDZ-binding motif, with high-virulence viral proteins bearing a refined PDZ-binding motif. Conclusions Our refined definition of PDZ-binding motifs should provide important clues for identifying functional PDZ-binding motifs and proteins involved in signal transduction.

  6. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  7. Fingerprint motifs of phytases | Fan | African Journal of Biotechnology

    African Journals Online (AJOL)

    Among the total of potential 173 phytases gained in 11 plant genomes through MAST, PAPhys are the major phytases, and HAPhys are the minor, and other phytase groups are not found in planta. Keywords: Phytase, fingerprint motif, multiple EM for motif elicitation (MEME), MAST African Journal of Biotechnology Vol.

  8. A Survey on PageRank Computing

    OpenAIRE

    Berkhin, Pavel

    2005-01-01

    This survey reviews the research related to PageRank computing. Components of a PageRank vector serve as authority weights for web pages independent of their textual content, solely based on the hyperlink structure of the web. PageRank is typically used as a web search ranking component. This defines the importance of the model and the data structures that underly PageRank processing. Computing even a single PageRank is a difficult computational task. Computing many PageRanks is a much mor...

  9. Short Arginine Motifs Drive Protein Stickiness in the Escherichia coli Cytoplasm.

    Science.gov (United States)

    Kyne, Ciara; Crowley, Peter B

    2017-09-19

    Although essential to numerous biotech applications, knowledge of molecular recognition by arginine-rich motifs in live cells remains limited. 1 H, 15 N HSQC and 19 F NMR spectroscopies were used to investigate the effects of C-terminal -GR n (n = 1-5) motifs on GB1 interactions in Escherichia coli cells and cell extracts. While the "biologically inert" GB1 yields high-quality in-cell spectra, the -GR n fusions with n = 4 or 5 were undetectable. This result suggests that a tetra-arginine motif is sufficient to drive interactions between a test protein and macromolecules in the E. coli cytoplasm. The inclusion of a 12 residue flexible linker between GB1 and the -GR 5 motif did not improve detection of the "inert" domain. In contrast, all of the constructs were detectable in cell lysates and extracts, suggesting that the arginine-mediated complexes were weak. Together these data reveal the significance of weak interactions between short arginine-rich motifs and the E. coli cytoplasm and demonstrate the potential of such motifs to modify protein interactions in living cells. These interactions must be considered in the design of (in vivo) nanoscale assemblies that rely on arginine-rich sequences.

  10. Anion induced conformational preference of Cα NN motif residues in functional proteins.

    Science.gov (United States)

    Patra, Piya; Ghosh, Mahua; Banerjee, Raja; Chakrabarti, Jaydeb

    2017-12-01

    Among different ligand binding motifs, anion binding C α NN motif consisting of peptide backbone atoms of three consecutive residues are observed to be important for recognition of free anions, like sulphate or biphosphate and participate in different key functions. Here we study the interaction of sulphate and biphosphate with C α NN motif present in different proteins. Instead of total protein, a peptide fragment has been studied keeping C α NN motif flanked in between other residues. We use classical force field based molecular dynamics simulations to understand the stability of this motif. Our data indicate fluctuations in conformational preferences of the motif residues in absence of the anion. The anion gives stability to one of these conformations. However, the anion induced conformational preferences are highly sequence dependent and specific to the type of anion. In particular, the polar residues are more favourable compared to the other residues for recognising the anion. © 2017 Wiley Periodicals, Inc.

  11. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

    Science.gov (United States)

    Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

    2018-04-01

    The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

  12. Finding a Leucine in a Haystack: Searching the Proteome for ambigous Leucine-Aspartic Acid motifs

    KAUST Repository

    Arold, Stefan T.

    2016-01-25

    Leucine-aspartic acid (LD) motifs are short helical protein-protein interaction motifs involved in cell motility, survival and communication. LD motif interactions are also implicated in cancer metastasis and are targeted by several viruses. LD motifs are notoriously difficult to detect because sequence pattern searches lead to an excessively high number of false positives. Hence, despite 20 years of research, only six LD motif–containing proteins are known in humans, three of which are close homologues of the paxillin family. To enable the proteome-wide discovery of LD motifs, we developed LD Motif Finder (LDMF), a web tool based on machine learning that combines sequence information with structural predictions to detect LD motifs with high accuracy. LDMF predicted 13 new LD motifs in humans. Using biophysical assays, we experimentally confirmed in vitro interactions for four novel LD motif proteins. Thus, LDMF allows proteome-wide discovery of LD motifs, despite a highly ambiguous sequence pattern. Functional implications will be discussed.

  13. Wikipedia ranking of world universities

    Science.gov (United States)

    Lages, José; Patt, Antoine; Shepelyansky, Dima L.

    2016-03-01

    We use the directed networks between articles of 24 Wikipedia language editions for producing the wikipedia ranking of world Universities (WRWU) using PageRank, 2DRank and CheiRank algorithms. This approach allows to incorporate various cultural views on world universities using the mathematical statistical analysis independent of cultural preferences. The Wikipedia ranking of top 100 universities provides about 60% overlap with the Shanghai university ranking demonstrating the reliable features of this approach. At the same time WRWU incorporates all knowledge accumulated at 24 Wikipedia editions giving stronger highlights for historically important universities leading to a different estimation of efficiency of world countries in university education. The historical development of university ranking is analyzed during ten centuries of their history.

  14. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures.

    Science.gov (United States)

    Someswara Rao, Chinta; Viswanadha Raju, S

    2016-03-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship between the H. sapiens and monkey. This similarity will be helpful at theft identification, maternity identification, disease identification, etc.

  15. CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures

    Directory of Open Access Journals (Sweden)

    Hamed Bostan

    2012-01-01

    Full Text Available Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.

  16. Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

    Science.gov (United States)

    Diaz de Arce, Alexander J; Noderer, William L; Wang, Clifford L

    2018-01-25

    The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. BEAM web server: a tool for structural RNA motif discovery.

    Science.gov (United States)

    Pietrosanto, Marco; Adinolfi, Marta; Casula, Riccardo; Ausiello, Gabriele; Ferrè, Fabrizio; Helmer-Citterich, Manuela

    2018-03-15

    RNA structural motif finding is a relevant problem that becomes computationally hard when working on high-throughput data (e.g. eCLIP, PAR-CLIP), often represented by thousands of RNA molecules. Currently, the BEAM server is the only web tool capable to handle tens of thousands of RNA in input with a motif discovery procedure that is only limited by the current secondary structure prediction accuracies. The recently developed method BEAM (BEAr Motifs finder) can analyze tens of thousands of RNA molecules and identify RNA secondary structure motifs associated to a measure of their statistical significance. BEAM is extremely fast thanks to the BEAR encoding that transforms each RNA secondary structure in a string of characters. BEAM also exploits the evolutionary knowledge contained in a substitution matrix of secondary structure elements, extracted from the RFAM database of families of homologous RNAs. The BEAM web server has been designed to streamline data pre-processing by automatically handling folding and encoding of RNA sequences, giving users a choice for the preferred folding program. The server provides an intuitive and informative results page with the list of secondary structure motifs identified, the logo of each motif, its significance, graphic representation and information about its position in the RNA molecules sharing it. The web server is freely available at http://beam.uniroma2.it/ and it is implemented in NodeJS and Python with all major browsers supported. marco.pietrosanto@uniroma2.it. Supplementary data are available at Bioinformatics online.

  18. Review article: The mountain motif in the plot of Matthew

    Directory of Open Access Journals (Sweden)

    Gert J. Volschenk

    2010-09-01

    Full Text Available This article reviewed T.L. Donaldson’s book, Jesus on the mountain: A study in Matthean theology, published in 1985 by JSOT Press, Sheffield, and focused on the mountain motif in the structure and plot of the Gospel of Matthew, in addition to the work of Donaldson on the mountain motif as a literary motif and as theological symbol. The mountain is a primary theological setting for Jesus’ ministry and thus is an important setting, serving as one of the literary devices by which Matthew structured and progressed his narrative. The Zion theological and eschatological significance and Second Temple Judaism serve as the historical and theological background for the mountain motif. The last mountain setting (Mt 28:16–20 is the culmination of the three theological themes in the plot of Matthew, namely Christology, ecclesiology and salvation history.

  19. Does resident ranking during recruitment accurately predict subsequent performance as a surgical resident?

    Science.gov (United States)

    Fryer, Jonathan P; Corcoran, Noreen; George, Brian; Wang, Ed; Darosa, Debra

    2012-01-01

    While the primary goal of ranking applicants for surgical residency training positions is to identify the candidates who will subsequently perform best as surgical residents, the effectiveness of the ranking process has not been adequately studied. We evaluated our general surgery resident recruitment process between 2001 and 2011 inclusive, to determine if our recruitment ranking parameters effectively predicted subsequent resident performance. We identified 3 candidate ranking parameters (United States Medical Licensing Examination [USMLE] Step 1 score, unadjusted ranking score [URS], and final adjusted ranking [FAR]), and 4 resident performance parameters (American Board of Surgery In-Training Examination [ABSITE] score, PGY1 resident evaluation grade [REG], overall REG, and independent faculty rating ranking [IFRR]), and assessed whether the former were predictive of the latter. Analyses utilized Spearman correlation coefficient. We found that the URS, which is based on objective and criterion based parameters, was a better predictor of subsequent performance than the FAR, which is a modification of the URS based on subsequent determinations of the resident selection committee. USMLE score was a reliable predictor of ABSITE scores only. However, when we compared our worst residence performances with the performances of the other residents in this evaluation, the data did not produce convincing evidence that poor resident performances could be reliably predicted by any of the recruitment ranking parameters. Finally, stratifying candidates based on their rank range did not effectively define a ranking cut-off beyond which resident performance would drop off. Based on these findings, we recommend surgery programs may be better served by utilizing a more structured resident ranking process and that subsequent adjustments to the rank list generated by this process should be undertaken with caution. Copyright © 2012 Association of Program Directors in Surgery

  20. Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences

    Science.gov (United States)

    König, Sebastian L. B.; Huppert, Julian L.; Sigel, Roland K. O.; Evans, Amanda C.

    2013-01-01

    G-quadruplexes and i-motifs are complementary examples of non-canonical nucleic acid substructure conformations. G-quadruplex thermodynamic stability has been extensively studied for a variety of base sequences, but the degree of duplex destabilization that adjacent quadruplex structure formation can cause has yet to be fully addressed. Stable in vivo formation of these alternative nucleic acid structures is likely to be highly dependent on whether sufficient spacing exists between neighbouring duplex- and quadruplex-/i-motif-forming regions to accommodate quadruplexes or i-motifs without disrupting duplex stability. Prediction of putative G-quadruplex-forming regions is likely to be assisted by further understanding of what distance (number of base pairs) is required for duplexes to remain stable as quadruplexes or i-motifs form. Using oligonucleotide constructs derived from precedented G-quadruplexes and i-motif-forming bcl-2 P1 promoter region, initial biophysical stability studies indicate that the formation of G-quadruplex and i-motif conformations do destabilize proximal duplex regions. The undermining effect that quadruplex formation can have on duplex stability is mitigated with increased distance from the duplex region: a spacing of five base pairs or more is sufficient to maintain duplex stability proximal to predicted quadruplex/i-motif-forming regions. PMID:23771141

  1. Systematic comparison of the response properties of protein and RNA mediated gene regulatory motifs.

    Science.gov (United States)

    Iyengar, Bharat Ravi; Pillai, Beena; Venkatesh, K V; Gadgil, Chetan J

    2017-05-30

    We present a framework enabling the dissection of the effects of motif structure (feedback or feedforward), the nature of the controller (RNA or protein), and the regulation mode (transcriptional, post-transcriptional or translational) on the response to a step change in the input. We have used a common model framework for gene expression where both motif structures have an activating input and repressing regulator, with the same set of parameters, to enable a comparison of the responses. We studied the global sensitivity of the system properties, such as steady-state gain, overshoot, peak time, and peak duration, to parameters. We find that, in all motifs, overshoot correlated negatively whereas peak duration varied concavely with peak time. Differences in the other system properties were found to be mainly dependent on the nature of the controller rather than the motif structure. Protein mediated motifs showed a higher degree of adaptation i.e. a tendency to return to baseline levels; in particular, feedforward motifs exhibited perfect adaptation. RNA mediated motifs had a mild regulatory effect; they also exhibited a lower peaking tendency and mean overshoot. Protein mediated feedforward motifs showed higher overshoot and lower peak time compared to the corresponding feedback motifs.

  2. Annotating RNA motifs in sequences and alignments.

    Science.gov (United States)

    Gardner, Paul P; Eldai, Hisham

    2015-01-01

    RNA performs a diverse array of important functions across all cellular life. These functions include important roles in translation, building translational machinery and maturing messenger RNA. More recent discoveries include the miRNAs and bacterial sRNAs that regulate gene expression, the thermosensors, riboswitches and other cis-regulatory elements that help prokaryotes sense their environment and eukaryotic piRNAs that suppress transposition. However, there can be a long period between the initial discovery of a RNA and determining its function. We present a bioinformatic approach to characterize RNA motifs, which are critical components of many RNA structure-function relationships. These motifs can, in some instances, provide researchers with functional hypotheses for uncharacterized RNAs. Moreover, we introduce a new profile-based database of RNA motifs--RMfam--and illustrate some applications for investigating the evolution and functional characterization of RNA. All the data and scripts associated with this work are available from: https://github.com/ppgardne/RMfam. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Fast social-like learning of complex behaviors based on motor motifs

    Science.gov (United States)

    Calvo Tapia, Carlos; Tyukin, Ivan Y.; Makarov, Valeri A.

    2018-05-01

    Social learning is widely observed in many species. Less experienced agents copy successful behaviors exhibited by more experienced individuals. Nevertheless, the dynamical mechanisms behind this process remain largely unknown. Here we assume that a complex behavior can be decomposed into a sequence of n motor motifs. Then a neural network capable of activating motor motifs in a given sequence can drive an agent. To account for (n -1 )! possible sequences of motifs in a neural network, we employ the winnerless competition approach. We then consider a teacher-learner situation: one agent exhibits a complex movement, while another one aims at mimicking the teacher's behavior. Despite the huge variety of possible motif sequences we show that the learner, equipped with the provided learning model, can rewire "on the fly" its synaptic couplings in no more than (n -1 ) learning cycles and converge exponentially to the durations of the teacher's motifs. We validate the learning model on mobile robots. Experimental results show that the learner is indeed capable of copying the teacher's behavior composed of six motor motifs in a few learning cycles. The reported mechanism of learning is general and can be used for replicating different functions, including, for example, sound patterns or speech.

  4. Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain.

    Directory of Open Access Journals (Sweden)

    Tingjun Hou

    2006-01-01

    Full Text Available Protein-protein interactions, particularly weak and transient ones, are often mediated by peptide recognition domains, such as Src Homology 2 and 3 (SH2 and SH3 domains, which bind to specific sequence and structural motifs. It is important but challenging to determine the binding specificity of these domains accurately and to predict their physiological interacting partners. In this study, the interactions between 35 peptide ligands (15 binders and 20 non-binders and the Abl SH3 domain were analyzed using molecular dynamics simulation and the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. The calculated binding free energies correlated well with the rank order of the binding peptides and clearly distinguished binders from non-binders. Free energy component analysis revealed that the van der Waals interactions dictate the binding strength of peptides, whereas the binding specificity is determined by the electrostatic interaction and the polar contribution of desolvation. The binding motif of the Abl SH3 domain was then determined by a virtual mutagenesis method, which mutates the residue at each position of the template peptide relative to all other 19 amino acids and calculates the binding free energy difference between the template and the mutated peptides using the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. A single position mutation free energy profile was thus established and used as a scoring matrix to search peptides recognized by the Abl SH3 domain in the human genome. Our approach successfully picked ten out of 13 experimentally determined binding partners of the Abl SH3 domain among the top 600 candidates from the 218,540 decapeptides with the PXXP motif in the SWISS-PROT database. We expect that this physical-principle based method can be applied to other protein domains as well.

  5. University Rankings and Social Science

    OpenAIRE

    Marginson, S.

    2014-01-01

    University rankings widely affect the behaviours of prospective students and their families, university executive leaders, academic faculty, governments and investors in higher education. Yet the social science foundations of global rankings receive little scrutiny. Rankings that simply recycle reputation without any necessary connection to real outputs are of no common value. It is necessary that rankings be soundly based in scientific terms if a virtuous relationship between performance and...

  6. Thermal Stability of Modified i-Motif Oligonucleotides with Naphthalimide Intercalating Nucleic Acids

    DEFF Research Database (Denmark)

    El-Sayed, Ahmed Ali; Pedersen, Erik B.; Khaireldin, Nahid Y.

    2016-01-01

    In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion of naphtha......In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion...... of naphthalimide (1H-benzo[de]isoquinoline-1,3(2H)-dione) as the intercalating nucleic acid. The stabilities of i-motif structures with inserted naphthalimide intercalating nucleotides were studied using UV melting temperatures (Tm) and circular dichroism spectra at different pH values and conditions (crowding...

  7. 24 CFR 599.401 - Ranking of applications.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Ranking of applications. 599.401... Communities § 599.401 Ranking of applications. (a) Ranking order. Rural and urban applications will be ranked... applications ranked first. (b) Separate ranking categories. After initial ranking, both rural and urban...

  8. WildSpan: mining structured motifs from protein sequences

    Directory of Open Access Journals (Sweden)

    Chen Chien-Yu

    2011-03-01

    Full Text Available Abstract Background Automatic extraction of motifs from biological sequences is an important research problem in study of molecular biology. For proteins, it is desired to discover sequence motifs containing a large number of wildcard symbols, as the residues associated with functional sites are usually largely separated in sequences. Discovering such patterns is time-consuming because abundant combinations exist when long gaps (a gap consists of one or more successive wildcards are considered. Mining algorithms often employ constraints to narrow down the search space in order to increase efficiency. However, improper constraint models might degrade the sensitivity and specificity of the motifs discovered by computational methods. We previously proposed a new constraint model to handle large wildcard regions for discovering functional motifs of proteins. The patterns that satisfy the proposed constraint model are called W-patterns. A W-pattern is a structured motif that groups motif symbols into pattern blocks interleaved with large irregular gaps. Considering large gaps reflects the fact that functional residues are not always from a single region of protein sequences, and restricting motif symbols into clusters corresponds to the observation that short motifs are frequently present within protein families. To efficiently discover W-patterns for large-scale sequence annotation and function prediction, this paper first formally introduces the problem to solve and proposes an algorithm named WildSpan (sequential pattern mining across large wildcard regions that incorporates several pruning strategies to largely reduce the mining cost. Results WildSpan is shown to efficiently find W-patterns containing conserved residues that are far separated in sequences. We conducted experiments with two mining strategies, protein-based and family-based mining, to evaluate the usefulness of W-patterns and performance of WildSpan. The protein-based mining mode

  9. Motif formation and industry specific topologies in the Japanese business firm network

    Science.gov (United States)

    Maluck, Julian; Donner, Reik V.; Takayasu, Hideki; Takayasu, Misako

    2017-05-01

    Motifs and roles are basic quantities for the characterization of interactions among 3-node subsets in complex networks. In this work, we investigate how the distribution of 3-node motifs can be influenced by modifying the rules of an evolving network model while keeping the statistics of simpler network characteristics, such as the link density and the degree distribution, invariant. We exemplify this problem for the special case of the Japanese Business Firm Network, where a well-studied and relatively simple yet realistic evolving network model is available, and compare the resulting motif distribution in the real-world and simulated networks. To better approximate the motif distribution of the real-world network in the model, we introduce both subgraph dependent and global additional rules. We find that a specific rule that allows only for the merging process between nodes with similar link directionality patterns reduces the observed excess of densely connected motifs with bidirectional links. Our study improves the mechanistic understanding of motif formation in evolving network models to better describe the characteristic features of real-world networks with a scale-free topology.

  10. On Page Rank

    NARCIS (Netherlands)

    Hoede, C.

    In this paper the concept of page rank for the world wide web is discussed. The possibility of describing the distribution of page rank by an exponential law is considered. It is shown that the concept is essentially equal to that of status score, a centrality measure discussed already in 1953 by

  11. Citation graph based ranking in Invenio

    CERN Document Server

    Marian, Ludmila; Rajman, Martin; Vesely, Martin

    2010-01-01

    Invenio is the web-based integrated digital library system developed at CERN. Within this framework, we present four types of ranking models based on the citation graph that complement the simple approach based on citation counts: time-dependent citation counts, a relevancy ranking which extends the PageRank model, a time-dependent ranking which combines the freshness of citations with PageRank and a ranking that takes into consideration the external citations. We present our analysis and results obtained on two main data sets: Inspire and CERN Document Server. Our main contributions are: (i) a study of the currently available ranking methods based on the citation graph; (ii) the development of new ranking methods that correct some of the identified limitations of the current methods such as treating all citations of equal importance, not taking time into account or considering the citation graph complete; (iii) a detailed study of the key parameters for these ranking methods. (The original publication is ava...

  12. Binding properties of SUMO-interacting motifs (SIMs) in yeast.

    Science.gov (United States)

    Jardin, Christophe; Horn, Anselm H C; Sticht, Heinrich

    2015-03-01

    Small ubiquitin-like modifier (SUMO) conjugation and interaction play an essential role in many cellular processes. A large number of yeast proteins is known to interact non-covalently with SUMO via short SUMO-interacting motifs (SIMs), but the structural details of this interaction are yet poorly characterized. In the present work, sequence analysis of a large dataset of 148 yeast SIMs revealed the existence of a hydrophobic core binding motif and a preference for acidic residues either within or adjacent to the core motif. Thus the sequence properties of yeast SIMs are highly similar to those described for human. Molecular dynamics simulations were performed to investigate the binding preferences for four representative SIM peptides differing in the number and distribution of acidic residues. Furthermore, the relative stability of two previously observed alternative binding orientations (parallel, antiparallel) was assessed. For all SIMs investigated, the antiparallel binding mode remained stable in the simulations and the SIMs were tightly bound via their hydrophobic core residues supplemented by polar interactions of the acidic residues. In contrary, the stability of the parallel binding mode is more dependent on the sequence features of the SIM motif like the number and position of acidic residues or the presence of additional adjacent interaction motifs. This information should be helpful to enhance the prediction of SIMs and their binding properties in different organisms to facilitate the reconstruction of the SUMO interactome.

  13. From benchmarking HITS-CLIP peak detection programs to a new method for identification of miRNA-binding sites from Ago2-CLIP data.

    Science.gov (United States)

    Bottini, Silvia; Hamouda-Tekaya, Nedra; Tanasa, Bogdan; Zaragosi, Laure-Emmanuelle; Grandjean, Valerie; Repetto, Emanuela; Trabucchi, Michele

    2017-05-19

    Experimental evidence indicates that about 60% of miRNA-binding activity does not follow the canonical rule about the seed matching between miRNA and target mRNAs, but rather a non-canonical miRNA targeting activity outside the seed or with a seed-like motifs. Here, we propose a new unbiased method to identify canonical and non-canonical miRNA-binding sites from peaks identified by Ago2 Cross-Linked ImmunoPrecipitation associated to high-throughput sequencing (CLIP-seq). Since the quality of peaks is of pivotal importance for the final output of the proposed method, we provide a comprehensive benchmarking of four peak detection programs, namely CIMS, PIPE-CLIP, Piranha and Pyicoclip, on four publicly available Ago2-HITS-CLIP datasets and one unpublished in-house Ago2-dataset in stem cells. We measured the sensitivity, the specificity and the position accuracy toward miRNA binding sites identification, and the agreement with TargetScan. Secondly, we developed a new pipeline, called miRBShunter, to identify canonical and non-canonical miRNA-binding sites based on de novo motif identification from Ago2 peaks and prediction of miRNA::RNA heteroduplexes. miRBShunter was tested and experimentally validated on the in-house Ago2-dataset and on an Ago2-PAR-CLIP dataset in human stem cells. Overall, we provide guidelines to choose a suitable peak detection program and a new method for miRNA-target identification. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Efficient sequential and parallel algorithms for finding edit distance based motifs.

    Science.gov (United States)

    Pal, Soumitra; Xiao, Peng; Rajasekaran, Sanguthevar

    2016-08-18

    Motif search is an important step in extracting meaningful patterns from biological data. The general problem of motif search is intractable and there is a pressing need to develop efficient, exact and approximation algorithms to solve this problem. In this paper, we present several novel, exact, sequential and parallel algorithms for solving the (l,d) Edit-distance-based Motif Search (EMS) problem: given two integers l,d and n biological strings, find all strings of length l that appear in each input string with atmost d errors of types substitution, insertion and deletion. One popular technique to solve the problem is to explore for each input string the set of all possible l-mers that belong to the d-neighborhood of any substring of the input string and output those which are common for all input strings. We introduce a novel and provably efficient neighborhood exploration technique. We show that it is enough to consider the candidates in neighborhood which are at a distance exactly d. We compactly represent these candidate motifs using wildcard characters and efficiently explore them with very few repetitions. Our sequential algorithm uses a trie based data structure to efficiently store and sort the candidate motifs. Our parallel algorithm in a multi-core shared memory setting uses arrays for storing and a novel modification of radix-sort for sorting the candidate motifs. The algorithms for EMS are customarily evaluated on several challenging instances such as (8,1), (12,2), (16,3), (20,4), and so on. The best previously known algorithm, EMS1, is sequential and in estimated 3 days solves up to instance (16,3). Our sequential algorithms are more than 20 times faster on (16,3). On other hard instances such as (9,2), (11,3), (13,4), our algorithms are much faster. Our parallel algorithm has more than 600 % scaling performance while using 16 threads. Our algorithms have pushed up the state-of-the-art of EMS solvers and we believe that the techniques introduced in

  15. Physical-chemical property based sequence motifs and methods regarding same

    Science.gov (United States)

    Braun, Werner [Friendswood, TX; Mathura, Venkatarajan S [Sarasota, FL; Schein, Catherine H [Friendswood, TX

    2008-09-09

    A data analysis system, program, and/or method, e.g., a data mining/data exploration method, using physical-chemical property motifs. For example, a sequence database may be searched for identifying segments thereof having physical-chemical properties similar to the physical-chemical property motifs.

  16. Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs.

    Science.gov (United States)

    Regad, Leslie; Martin, Juliette; Camproux, Anne-Claude

    2011-06-20

    One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function. Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model - Structural Alphabet), which allows simplification of protein structures into uni-dimensional sequences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i) ubiquitous motifs, shared by several superfamilies and (ii) superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P) and SAH/SAM. Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.

  17. Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2011-06-01

    Full Text Available Abstract Background One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function. Results Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model - Structural Alphabet, which allows simplification of protein structures into uni-dimensional sequences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i ubiquitous motifs, shared by several superfamilies and (ii superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P and SAH/SAM. Conclusions Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.

  18. Functional identification of a Lippia dulcis bornyl diphosphate synthase that contains a duplicated, inhibitory arginine-rich motif.

    Science.gov (United States)

    Hurd, Matthew C; Kwon, Moonhyuk; Ro, Dae-Kyun

    2017-08-26

    Lippia dulcis (Aztec sweet herb) contains the potent natural sweetener hernandulcin, a sesquiterpene ketone found in the leaves and flowers. Utilizing the leaves for agricultural application is challenging due to the presence of the bitter-tasting and toxic monoterpene, camphor. To unlock the commercial potential of L. dulcis leaves, the first step of camphor biosynthesis by a bornyl diphosphate synthase needs to be elucidated. Two putative monoterpene synthases (LdTPS3 and LdTPS9) were isolated from L. dulcis leaf cDNA. To elucidate their catalytic functions, E. coli-produced recombinant enzymes with truncations of their chloroplast transit peptides were assayed with geranyl diphosphate (GPP). In vitro enzyme assays showed that LdTPS3 encodes bornyl diphosphate synthase (thus named LdBPPS) while LdTPS9 encodes linalool synthase. Interestingly, the N-terminus of LdBPPS possesses two arginine-rich (RRX 8 W) motifs, and enzyme assays showed that the presence of both RRX 8 W motifs completely inhibits the catalytic activity of LdBPPS. Only after the removal of the putative chloroplast transit peptide and the first RRX 8 W, LdBPPS could react with GPP to produce bornyl diphosphate. LdBPPS is distantly related to the known bornyl diphosphate synthase from sage in a phylogenetic analysis, indicating a converged evolution of camphor biosynthesis in sage and L. dulcis. The discovery of LdBPPS opens up the possibility of engineering L. dulcis to remove the undesirable product, camphor. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Finding differentially expressed genes in high dimensional data: Rank based test statistic via a distance measure.

    Science.gov (United States)

    Mathur, Sunil; Sadana, Ajit

    2015-12-01

    We present a rank-based test statistic for the identification of differentially expressed genes using a distance measure. The proposed test statistic is highly robust against extreme values and does not assume the distribution of parent population. Simulation studies show that the proposed test is more powerful than some of the commonly used methods, such as paired t-test, Wilcoxon signed rank test, and significance analysis of microarray (SAM) under certain non-normal distributions. The asymptotic distribution of the test statistic, and the p-value function are discussed. The application of proposed method is shown using a real-life data set. © The Author(s) 2011.

  20. When sparse coding meets ranking: a joint framework for learning sparse codes and ranking scores

    KAUST Repository

    Wang, Jim Jing-Yan

    2017-06-28

    Sparse coding, which represents a data point as a sparse reconstruction code with regard to a dictionary, has been a popular data representation method. Meanwhile, in database retrieval problems, learning the ranking scores from data points plays an important role. Up to now, these two problems have always been considered separately, assuming that data coding and ranking are two independent and irrelevant problems. However, is there any internal relationship between sparse coding and ranking score learning? If yes, how to explore and make use of this internal relationship? In this paper, we try to answer these questions by developing the first joint sparse coding and ranking score learning algorithm. To explore the local distribution in the sparse code space, and also to bridge coding and ranking problems, we assume that in the neighborhood of each data point, the ranking scores can be approximated from the corresponding sparse codes by a local linear function. By considering the local approximation error of ranking scores, the reconstruction error and sparsity of sparse coding, and the query information provided by the user, we construct a unified objective function for learning of sparse codes, the dictionary and ranking scores. We further develop an iterative algorithm to solve this optimization problem.

  1. University Rankings: The Web Ranking

    Science.gov (United States)

    Aguillo, Isidro F.

    2012-01-01

    The publication in 2003 of the Ranking of Universities by Jiao Tong University of Shanghai has revolutionized not only academic studies on Higher Education, but has also had an important impact on the national policies and the individual strategies of the sector. The work gathers the main characteristics of this and other global university…

  2. Ranking Specific Sets of Objects.

    Science.gov (United States)

    Maly, Jan; Woltran, Stefan

    2017-01-01

    Ranking sets of objects based on an order between the single elements has been thoroughly studied in the literature. In particular, it has been shown that it is in general impossible to find a total ranking - jointly satisfying properties as dominance and independence - on the whole power set of objects. However, in many applications certain elements from the entire power set might not be required and can be neglected in the ranking process. For instance, certain sets might be ruled out due to hard constraints or are not satisfying some background theory. In this paper, we treat the computational problem whether an order on a given subset of the power set of elements satisfying different variants of dominance and independence can be found, given a ranking on the elements. We show that this problem is tractable for partial rankings and NP-complete for total rankings.

  3. Organization of feed-forward loop motifs reveals architectural principles in natural and engineered networks.

    Science.gov (United States)

    Gorochowski, Thomas E; Grierson, Claire S; di Bernardo, Mario

    2018-03-01

    Network motifs are significantly overrepresented subgraphs that have been proposed as building blocks for natural and engineered networks. Detailed functional analysis has been performed for many types of motif in isolation, but less is known about how motifs work together to perform complex tasks. To address this issue, we measure the aggregation of network motifs via methods that extract precisely how these structures are connected. Applying this approach to a broad spectrum of networked systems and focusing on the widespread feed-forward loop motif, we uncover striking differences in motif organization. The types of connection are often highly constrained, differ between domains, and clearly capture architectural principles. We show how this information can be used to effectively predict functionally important nodes in the metabolic network of Escherichia coli . Our findings have implications for understanding how networked systems are constructed from motif parts and elucidate constraints that guide their evolution.

  4. Development of the Operational Events Groups Ranking Tool

    International Nuclear Information System (INIS)

    Simic, Zdenko; Banov, Reni

    2014-01-01

    Both because of complexity and ageing, facilities like nuclear power plants require feedback from the operating experience in order to further improve safety and operation performance. That is the reason why significant effort is dedicated to operating experience feedback. This paper contains description of the specification and development of the application for the operating events ranking software tool. Robust and consistent way of selecting most important events for detail investigation is important because it is not feasible or even useful to investigate all of them. Development of the tool is based on the comprehensive events characterisation and methodical prioritization. This includes rich set of events parameters which allow their top level preliminary analysis, different ways of groupings and even to evaluate uncertainty propagation to the ranking results. One distinct feature of the implemented method is that user (i.e., expert) could determine how important is particular ranking parameter based on their pairwise comparison. For tools demonstration and usability it is crucial that sample database is also created. For useful analysis the whole set of events for 5 years is selected and characterised. Based on the preliminary results this tool seems valuable for new preliminary prospective on data as whole, and especially for the identification of events groups which should have priority in the more detailed assessment. The results are consisting of different informative views on the events groups importance and related sensitivity and uncertainty results. This presents valuable tool for improving overall picture about specific operating experience and also for helping identify the most important events groups for further assessment. It is clear that completeness and consistency of the input data characterisation is very important to get full and valuable importance ranking. Method and tool development described in this paper is part of continuous effort of

  5. PageRank of integers

    International Nuclear Information System (INIS)

    Frahm, K M; Shepelyansky, D L; Chepelianskii, A D

    2012-01-01

    We up a directed network tracing links from a given integer to its divisors and analyze the properties of the Google matrix of this network. The PageRank vector of this matrix is computed numerically and it is shown that its probability is approximately inversely proportional to the PageRank index thus being similar to the Zipf law and the dependence established for the World Wide Web. The spectrum of the Google matrix of integers is characterized by a large gap and a relatively small number of nonzero eigenvalues. A simple semi-analytical expression for the PageRank of integers is derived that allows us to find this vector for matrices of billion size. This network provides a new PageRank order of integers. (paper)

  6. Canine length in wild male baboons: maturation, aging and social dominance rank.

    Directory of Open Access Journals (Sweden)

    Jordi Galbany

    Full Text Available Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank, but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  7. RSAT matrix-clustering: dynamic exploration and redundancy reduction of transcription factor binding motif collections.

    Science.gov (United States)

    Castro-Mondragon, Jaime Abraham; Jaeger, Sébastien; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

    2017-07-27

    Transcription factor (TF) databases contain multitudes of binding motifs (TFBMs) from various sources, from which non-redundant collections are derived by manual curation. The advent of high-throughput methods stimulated the production of novel collections with increasing numbers of motifs. Meta-databases, built by merging these collections, contain redundant versions, because available tools are not suited to automatically identify and explore biologically relevant clusters among thousands of motifs. Motif discovery from genome-scale data sets (e.g. ChIP-seq) also produces redundant motifs, hampering the interpretation of results. We present matrix-clustering, a versatile tool that clusters similar TFBMs into multiple trees, and automatically creates non-redundant TFBM collections. A feature unique to matrix-clustering is its dynamic visualisation of aligned TFBMs, and its capability to simultaneously treat multiple collections from various sources. We demonstrate that matrix-clustering considerably simplifies the interpretation of combined results from multiple motif discovery tools, and highlights biologically relevant variations of similar motifs. We also ran a large-scale application to cluster ∼11 000 motifs from 24 entire databases, showing that matrix-clustering correctly groups motifs belonging to the same TF families, and drastically reduced motif redundancy. matrix-clustering is integrated within the RSAT suite (http://rsat.eu/), accessible through a user-friendly web interface or command-line for its integration in pipelines. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Fuzzy Evidence in Identification, Forecasting and Diagnosis

    CERN Document Server

    Rotshtein, Alexander P

    2012-01-01

    The purpose of this book is to present a methodology for designing and tuning fuzzy expert systems in order to identify nonlinear objects; that is, to build input-output models using expert and experimental information. The results of these identifications are used for direct and inverse fuzzy evidence in forecasting and diagnosis problem solving. The book is organised as follows: Chapter 1 presents the basic knowledge about fuzzy sets, genetic algorithms and neural nets necessary for a clear understanding of the rest of this book. Chapter 2 analyzes direct fuzzy inference based on fuzzy if-then rules. Chapter 3 is devoted to the tuning of fuzzy rules for direct inference using genetic algorithms and neural nets. Chapter 4 presents models and algorithms for extracting fuzzy rules from experimental data. Chapter 5 describes a method for solving fuzzy logic equations necessary for the inverse fuzzy inference in diagnostic systems. Chapters 6 and 7 are devoted to inverse fuzzy inference based on fu...

  9. Ranking Support Vector Machine with Kernel Approximation.

    Science.gov (United States)

    Chen, Kai; Li, Rongchun; Dou, Yong; Liang, Zhengfa; Lv, Qi

    2017-01-01

    Learning to rank algorithm has become important in recent years due to its successful application in information retrieval, recommender system, and computational biology, and so forth. Ranking support vector machine (RankSVM) is one of the state-of-art ranking models and has been favorably used. Nonlinear RankSVM (RankSVM with nonlinear kernels) can give higher accuracy than linear RankSVM (RankSVM with a linear kernel) for complex nonlinear ranking problem. However, the learning methods for nonlinear RankSVM are still time-consuming because of the calculation of kernel matrix. In this paper, we propose a fast ranking algorithm based on kernel approximation to avoid computing the kernel matrix. We explore two types of kernel approximation methods, namely, the Nyström method and random Fourier features. Primal truncated Newton method is used to optimize the pairwise L2-loss (squared Hinge-loss) objective function of the ranking model after the nonlinear kernel approximation. Experimental results demonstrate that our proposed method gets a much faster training speed than kernel RankSVM and achieves comparable or better performance over state-of-the-art ranking algorithms.

  10. Ranking Support Vector Machine with Kernel Approximation

    Directory of Open Access Journals (Sweden)

    Kai Chen

    2017-01-01

    Full Text Available Learning to rank algorithm has become important in recent years due to its successful application in information retrieval, recommender system, and computational biology, and so forth. Ranking support vector machine (RankSVM is one of the state-of-art ranking models and has been favorably used. Nonlinear RankSVM (RankSVM with nonlinear kernels can give higher accuracy than linear RankSVM (RankSVM with a linear kernel for complex nonlinear ranking problem. However, the learning methods for nonlinear RankSVM are still time-consuming because of the calculation of kernel matrix. In this paper, we propose a fast ranking algorithm based on kernel approximation to avoid computing the kernel matrix. We explore two types of kernel approximation methods, namely, the Nyström method and random Fourier features. Primal truncated Newton method is used to optimize the pairwise L2-loss (squared Hinge-loss objective function of the ranking model after the nonlinear kernel approximation. Experimental results demonstrate that our proposed method gets a much faster training speed than kernel RankSVM and achieves comparable or better performance over state-of-the-art ranking algorithms.

  11. University Rankings and Social Science

    Science.gov (United States)

    Marginson, Simon

    2014-01-01

    University rankings widely affect the behaviours of prospective students and their families, university executive leaders, academic faculty, governments and investors in higher education. Yet the social science foundations of global rankings receive little scrutiny. Rankings that simply recycle reputation without any necessary connection to real…

  12. Structural fragment clustering reveals novel structural and functional motifs in α-helical transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Vassilev Boris

    2010-04-01

    Full Text Available Abstract Background A large proportion of an organism's genome encodes for membrane proteins. Membrane proteins are important for many cellular processes, and several diseases can be linked to mutations in them. With the tremendous growth of sequence data, there is an increasing need to reliably identify membrane proteins from sequence, to functionally annotate them, and to correctly predict their topology. Results We introduce a technique called structural fragment clustering, which learns sequential motifs from 3D structural fragments. From over 500,000 fragments, we obtain 213 statistically significant, non-redundant, and novel motifs that are highly specific to α-helical transmembrane proteins. From these 213 motifs, 58 of them were assigned to function and checked in the scientific literature for a biological assessment. Seventy percent of the motifs are found in co-factor, ligand, and ion binding sites, 30% at protein interaction interfaces, and 12% bind specific lipids such as glycerol or cardiolipins. The vast majority of motifs (94% appear across evolutionarily unrelated families, highlighting the modularity of functional design in membrane proteins. We describe three novel motifs in detail: (1 a dimer interface motif found in voltage-gated chloride channels, (2 a proton transfer motif found in heme-copper oxidases, and (3 a convergently evolved interface helix motif found in an aspartate symporter, a serine protease, and cytochrome b. Conclusions Our findings suggest that functional modules exist in membrane proteins, and that they occur in completely different evolutionary contexts and cover different binding sites. Structural fragment clustering allows us to link sequence motifs to function through clusters of structural fragments. The sequence motifs can be applied to identify and characterize membrane proteins in novel genomes.

  13. Two-dimensional ranking of Wikipedia articles

    Science.gov (United States)

    Zhirov, A. O.; Zhirov, O. V.; Shepelyansky, D. L.

    2010-10-01

    The Library of Babel, described by Jorge Luis Borges, stores an enormous amount of information. The Library exists ab aeterno. Wikipedia, a free online encyclopaedia, becomes a modern analogue of such a Library. Information retrieval and ranking of Wikipedia articles become the challenge of modern society. While PageRank highlights very well known nodes with many ingoing links, CheiRank highlights very communicative nodes with many outgoing links. In this way the ranking becomes two-dimensional. Using CheiRank and PageRank we analyze the properties of two-dimensional ranking of all Wikipedia English articles and show that it gives their reliable classification with rich and nontrivial features. Detailed studies are done for countries, universities, personalities, physicists, chess players, Dow-Jones companies and other categories.

  14. [Cover motifs of the Tidsskrift. A 14-year cavalcade].

    Science.gov (United States)

    Nylenna, M

    1998-12-10

    In 1985 the Journal of the Norwegian Medical Association changed its cover policy, moving the table of contents inside the Journal and introducing cover illustrations. This article provides an analysis of all cover illustrations published over this 14-year period, 420 covers in all. There is a great variation in cover motifs and designs and a development towards more general motifs. The initial emphasis on historical and medical aspects is now less pronounced, while the use of works of art and nature motifs has increased, and the cover now more often has a direct bearing on the specific contents of the issue. Professor of medical history Oivind Larsen has photographed two thirds of the covers and contributed 95% of the inside essay-style reflections on the cover motif. Over the years, he has expanded the role of the historian of medicine disseminating knowledge to include that of the raconteur with a personal tone of voice. The Journal's covers are now one of its most characteristic features, emblematic of the Journal's ambition of standing for quality and timelessness vis-à-vis the news media, and of its aim of bridging the gap between medicine and the humanities.

  15. PageRank-based identification of signaling crosstalk from transcriptomics data: the case of Arabidopsis thaliana.

    Science.gov (United States)

    Omranian, Nooshin; Mueller-Roeber, Bernd; Nikoloski, Zoran

    2012-04-01

    The levels of cellular organization, from gene transcription to translation to protein-protein interaction and metabolism, operate via tightly regulated mutual interactions, facilitating organismal adaptability and various stress responses. Characterizing the mutual interactions between genes, transcription factors, and proteins involved in signaling, termed crosstalk, is therefore crucial for understanding and controlling cells' functionality. We aim at using high-throughput transcriptomics data to discover previously unknown links between signaling networks. We propose and analyze a novel method for crosstalk identification which relies on transcriptomics data and overcomes the lack of complete information for signaling pathways in Arabidopsis thaliana. Our method first employs a network-based transformation of the results from the statistical analysis of differential gene expression in given groups of experiments under different signal-inducing conditions. The stationary distribution of a random walk (similar to the PageRank algorithm) on the constructed network is then used to determine the putative transcripts interrelating different signaling pathways. With the help of the proposed method, we analyze a transcriptomics data set including experiments from four different stresses/signals: nitrate, sulfur, iron, and hormones. We identified promising gene candidates, downstream of the transcription factors (TFs), associated to signaling crosstalk, which were validated through literature mining. In addition, we conduct a comparative analysis with the only other available method in this field which used a biclustering-based approach. Surprisingly, the biclustering-based approach fails to robustly identify any candidate genes involved in the crosstalk of the analyzed signals. We demonstrate that our proposed method is more robust in identifying gene candidates involved downstream of the signaling crosstalk for species for which large transcriptomics data sets

  16. A DEA-TOPSIS approach for ranking credit institutions

    Directory of Open Access Journals (Sweden)

    Mohammad Ehsani

    2014-09-01

    Full Text Available Measuring the relative efficiency of financial units plays essential role for making strategic decisions such as business development, downsizing, etc. This paper presents an empirical investigation to rank different branches of a credit institution named Samen in city of Semnan, Iran. The proposed study uses data envelopment analysis (DEA for measuring the relative efficiency of 17 units. The results indicate that five units were efficient and using Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS, the efficient units are ranked based on some inputs/outputs. The results of this study indicate that most branches of this financial unit performed poorly and a restructure in their businesses is necessary. In addition, the study has provided some evidences that considering employee wage, bank deposit and administration expenses as inputs for DEA implementation seems to provide better results than using total assets and equities.

  17. Proteome-level assessment of origin, prevalence and function of Leucine-Aspartic Acid (LD) motifs

    KAUST Repository

    Alam, Tanvir

    2018-03-11

    Short Linear Motifs (SLiMs) contribute to almost every cellular function by connecting appropriate protein partners. Accurate prediction of SLiMs is difficult due to their shortness and sequence degeneracy. Leucine-aspartic acid (LD) motifs are SLiMs that link paxillin family proteins to factors controlling (cancer) cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood. To enable a proteome-wide assessment of these motifs, we developed an active-learning based framework that iteratively integrates computational predictions with experimental validation. Our analysis of the human proteome identified a dozen proteins that contain LD motifs, all being involved in cell adhesion and migration, and revealed a new type of inverse LD motif consensus. Our evolutionary analysis suggested that LD motif signalling originated in the common unicellular ancestor of opisthokonts and amoebozoa by co-opting nuclear export sequences. Inter-species comparison revealed a conserved LD signalling core, and reveals the emergence of species-specific adaptive connections, while maintaining a strong functional focus of the LD motif interactome. Collectively, our data elucidate the mechanisms underlying the origin and adaptation of an ancestral SLiM.

  18. Face the hierarchy: ERP and oscillatory brain responses in social rank processing.

    Science.gov (United States)

    Breton, Audrey; Jerbi, Karim; Henaff, Marie-Anne; Cheylus, Anne; Baudouin, Jean-Yves; Schmitz, Christina; Krolak-Salmon, Pierre; Van der Henst, Jean-Baptiste

    2014-01-01

    Recognition of social hierarchy is a key feature that helps us navigate through our complex social environment. Neuroimaging studies have identified brain structures involved in the processing of hierarchical stimuli but the precise temporal dynamics of brain activity associated with such processing remains largely unknown. Here, we used electroencephalography to examine the effect of social hierarchy on neural responses elicited by faces. In contrast to previous studies, the key manipulation was that a hierarchical context was constructed, not by varying facial expressions, but by presenting neutral-expression faces in a game setting. Once the performance-based hierarchy was established, participants were presented with high-rank, middle-rank and low-rank player faces and had to evaluate the rank of each face with respect to their own position. Both event-related potentials and task-related oscillatory activity were investigated. Three main findings emerge from the study. First, the experimental manipulation had no effect on the early N170 component, which may suggest that hierarchy did not modulate the structural encoding of neutral-expression faces. Second, hierarchy significantly modulated the amplitude of the late positive potential (LPP) within a 400-700 ms time-window, with more a prominent LPP occurring when the participants processed the face of the highest-rank player. Third, high-rank faces were associated with the highest reduction of alpha power. Taken together these findings provide novel electrophysiological evidence for enhanced allocation of attentional resource in the presence of high-rank faces. At a broader level, this study brings new insights into the neural processing underlying social categorization.

  19. 14 CFR 1214.1105 - Final ranking.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Final ranking. 1214.1105 Section 1214.1105... Recruitment and Selection Program § 1214.1105 Final ranking. Final rankings will be based on a combination of... preference will be included in this final ranking in accordance with applicable regulations. ...

  20. Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices.

    Science.gov (United States)

    Zanuy, David; Gunasekaran, Kannan; Lesk, Arthur M; Nussinov, Ruth

    2006-04-21

    The formation of fibril aggregates by long polyglutamine sequences is assumed to play a major role in neurodegenerative diseases such as Huntington. Here, we model peptides rich in glutamine, through a series of molecular dynamics simulations. Starting from a rigid nanotube-like conformation, we have obtained a new conformational template that shares structural features of a tubular helix and of a beta-helix conformational organization. Our new model can be described as a super-helical arrangement of flat beta-sheet segments linked by planar turns or bends. Interestingly, our comprehensive analysis of the Protein Data Bank reveals that this is a common motif in beta-helices (termed beta-bend), although it has not been identified so far. The motif is based on the alternation of beta-sheet and helical conformation as the protein sequence is followed from the N to the C termini (beta-alpha(R)-beta-polyPro-beta). We further identify this motif in the ssNMR structure of the protofibril of the amyloidogenic peptide Abeta(1-40). The recurrence of the beta-bend suggests a general mode of connecting long parallel beta-sheet segments that would allow the growth of partially ordered fibril structures. The design allows the peptide backbone to change direction with a minimal loss of main chain hydrogen bonds. The identification of a coherent organization beyond that of the beta-sheet segments in different folds rich in parallel beta-sheets suggests a higher degree of ordered structure in protein fibrils, in agreement with their low solubility and dense molecular packing.

  1. Leucine-based receptor sorting motifs are dependent on the spacing relative to the plasma membrane

    DEFF Research Database (Denmark)

    Geisler, C; Dietrich, J; Nielsen, B L

    1998-01-01

    Many integral membrane proteins contain leucine-based motifs within their cytoplasmic domains that mediate internalization and intracellular sorting. Two types of leucine-based motifs have been identified. One type is dependent on phosphorylation, whereas the other type, which includes an acidic...... amino acid, is constitutively active. In this study, we have investigated how the spacing relative to the plasma membrane affects the function of both types of leucine-based motifs. For phosphorylation-dependent leucine-based motifs, a minimal spacing of 7 residues between the plasma membrane...... and the phospho-acceptor was required for phosphorylation and thereby activation of the motifs. For constitutively active leucine-based motifs, a minimal spacing of 6 residues between the plasma membrane and the acidic residue was required for optimal activity of the motifs. In addition, we found that the acidic...

  2. Rank-based Tests of the Cointegrating Rank in Semiparametric Error Correction Models

    NARCIS (Netherlands)

    Hallin, M.; van den Akker, R.; Werker, B.J.M.

    2012-01-01

    Abstract: This paper introduces rank-based tests for the cointegrating rank in an Error Correction Model with i.i.d. elliptical innovations. The tests are asymptotically distribution-free, and their validity does not depend on the actual distribution of the innovations. This result holds despite the

  3. Universal scaling in sports ranking

    International Nuclear Information System (INIS)

    Deng Weibing; Li Wei; Cai Xu; Bulou, Alain; Wang Qiuping A

    2012-01-01

    Ranking is a ubiquitous phenomenon in human society. On the web pages of Forbes, one may find all kinds of rankings, such as the world's most powerful people, the world's richest people, the highest-earning tennis players, and so on and so forth. Herewith, we study a specific kind—sports ranking systems in which players' scores and/or prize money are accrued based on their performances in different matches. By investigating 40 data samples which span 12 different sports, we find that the distributions of scores and/or prize money follow universal power laws, with exponents nearly identical for most sports. In order to understand the origin of this universal scaling we focus on the tennis ranking systems. By checking the data we find that, for any pair of players, the probability that the higher-ranked player tops the lower-ranked opponent is proportional to the rank difference between the pair. Such a dependence can be well fitted to a sigmoidal function. By using this feature, we propose a simple toy model which can simulate the competition of players in different matches. The simulations yield results consistent with the empirical findings. Extensive simulation studies indicate that the model is quite robust with respect to the modifications of some parameters. (paper)

  4. Minkowski metrics in creating universal ranking algorithms

    Directory of Open Access Journals (Sweden)

    Andrzej Ameljańczyk

    2014-06-01

    Full Text Available The paper presents a general procedure for creating the rankings of a set of objects, while the relation of preference based on any ranking function. The analysis was possible to use the ranking functions began by showing the fundamental drawbacks of commonly used functions in the form of a weighted sum. As a special case of the ranking procedure in the space of a relation, the procedure based on the notion of an ideal element and generalized Minkowski distance from the element was proposed. This procedure, presented as universal ranking algorithm, eliminates most of the disadvantages of ranking functions in the form of a weighted sum.[b]Keywords[/b]: ranking functions, preference relation, ranking clusters, categories, ideal point, universal ranking algorithm

  5. Recurrent fuzzy ranking methods

    Science.gov (United States)

    Hajjari, Tayebeh

    2012-11-01

    With the increasing development of fuzzy set theory in various scientific fields and the need to compare fuzzy numbers in different areas. Therefore, Ranking of fuzzy numbers plays a very important role in linguistic decision-making, engineering, business and some other fuzzy application systems. Several strategies have been proposed for ranking of fuzzy numbers. Each of these techniques has been shown to produce non-intuitive results in certain case. In this paper, we reviewed some recent ranking methods, which will be useful for the researchers who are interested in this area.

  6. DistAMo: A web-based tool to characterize DNA-motif distribution on bacterial chromosomes

    Directory of Open Access Journals (Sweden)

    Patrick eSobetzko

    2016-03-01

    Full Text Available Short DNA motifs are involved in a multitude of functions such as for example chromosome segregation, DNA replication or mismatch repair. Distribution of such motifs is often not random and the specific chromosomal pattern relates to the respective motif function. Computational approaches which quantitatively assess such chromosomal motif patterns are necessary. Here we present a new computer tool DistAMo (Distribution Analysis of DNA Motifs. The algorithm uses codon redundancy to calculate the relative abundance of short DNA motifs from single genes to entire chromosomes. Comparative genomics analyses of the GATC-motif distribution in γ-proteobacterial genomes using DistAMo revealed that (i genes beside the replication origin are enriched in GATCs, (ii genome-wide GATC distribution follows a distinct pattern and (iii genes involved in DNA replication and repair are enriched in GATCs. These features are specific for bacterial chromosomes encoding a Dam methyltransferase. The new software is available as a stand-alone or as an easy-to-use web-based server version at http://www.computational.bio.uni-giessen.de/distamo.

  7. Ranking Operations Management conferences

    NARCIS (Netherlands)

    Steenhuis, H.J.; de Bruijn, E.J.; Gupta, Sushil; Laptaned, U

    2007-01-01

    Several publications have appeared in the field of Operations Management which rank Operations Management related journals. Several ranking systems exist for journals based on , for example, perceived relevance and quality, citation, and author affiliation. Many academics also publish at conferences

  8. Selection against spurious promoter motifs correlates withtranslational efficiency across bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Froula, Jeffrey L.; Francino, M. Pilar

    2007-05-01

    Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the {sigma}{sup 70} subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, -10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also implies that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria.

  9. Country-specific determinants of world university rankings

    OpenAIRE

    Pietrucha, Jacek

    2017-01-01

    This paper examines country-specific factors that affect the three most influential world university rankings (the Academic Ranking of World Universities, the QS World University Ranking, and the Times Higher Education World University Ranking). We run a cross sectional regression that covers 42–71 countries (depending on the ranking and data availability). We show that the position of universities from a country in the ranking is determined by the following country-specific variables: econom...

  10. AptRank: an adaptive PageRank model for protein function prediction on   bi-relational graphs.

    Science.gov (United States)

    Jiang, Biaobin; Kloster, Kyle; Gleich, David F; Gribskov, Michael

    2017-06-15

    Diffusion-based network models are widely used for protein function prediction using protein network data and have been shown to outperform neighborhood-based and module-based methods. Recent studies have shown that integrating the hierarchical structure of the Gene Ontology (GO) data dramatically improves prediction accuracy. However, previous methods usually either used the GO hierarchy to refine the prediction results of multiple classifiers, or flattened the hierarchy into a function-function similarity kernel. No study has taken the GO hierarchy into account together with the protein network as a two-layer network model. We first construct a Bi-relational graph (Birg) model comprised of both protein-protein association and function-function hierarchical networks. We then propose two diffusion-based methods, BirgRank and AptRank, both of which use PageRank to diffuse information on this two-layer graph model. BirgRank is a direct application of traditional PageRank with fixed decay parameters. In contrast, AptRank utilizes an adaptive diffusion mechanism to improve the performance of BirgRank. We evaluate the ability of both methods to predict protein function on yeast, fly and human protein datasets, and compare with four previous methods: GeneMANIA, TMC, ProteinRank and clusDCA. We design four different validation strategies: missing function prediction, de novo function prediction, guided function prediction and newly discovered function prediction to comprehensively evaluate predictability of all six methods. We find that both BirgRank and AptRank outperform the previous methods, especially in missing function prediction when using only 10% of the data for training. The MATLAB code is available at https://github.rcac.purdue.edu/mgribsko/aptrank . gribskov@purdue.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  11. Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.

    Science.gov (United States)

    Vishnevsky, Oleg V; Bocharnikov, Andrey V; Kolchanov, Nikolay A

    2018-02-01

    The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches. Unfortunately, the efficiency of the motif discovery programs dramatically declines with the query set size increase. This leads to the fact that only a fraction of top "peak" ChIP-Seq segments can be analyzed or the area of analysis should be narrowed. Thus, the motif discovery in massive datasets remains a challenging issue. Argo_Compute Unified Device Architecture (CUDA) web service is designed to process the massive DNA data. It is a program for the detection of degenerate oligonucleotide motifs of fixed length written in 15-letter IUPAC code. Argo_CUDA is a full-exhaustive approach based on the high-performance GPU technologies. Compared with the existing motif discovery web services, Argo_CUDA shows good prediction quality on simulated sets. The analysis of ChIP-Seq sequences revealed the motifs which correspond to known transcription factor binding sites.

  12. iFORM: Incorporating Find Occurrence of Regulatory Motifs.

    Science.gov (United States)

    Ren, Chao; Chen, Hebing; Yang, Bite; Liu, Feng; Ouyang, Zhangyi; Bo, Xiaochen; Shu, Wenjie

    2016-01-01

    Accurately identifying the binding sites of transcription factors (TFs) is crucial to understanding the mechanisms of transcriptional regulation and human disease. We present incorporating Find Occurrence of Regulatory Motifs (iFORM), an easy-to-use and efficient tool for scanning DNA sequences with TF motifs described as position weight matrices (PWMs). Both performance assessment with a receiver operating characteristic (ROC) curve and a correlation-based approach demonstrated that iFORM achieves higher accuracy and sensitivity by integrating five classical motif discovery programs using Fisher's combined probability test. We have used iFORM to provide accurate results on a variety of data in the ENCODE Project and the NIH Roadmap Epigenomics Project, and the tool has demonstrated its utility in further elucidating individual roles of functional elements. Both the source and binary codes for iFORM can be freely accessed at https://github.com/wenjiegroup/iFORM. The identified TF binding sites across human cell and tissue types using iFORM have been deposited in the Gene Expression Omnibus under the accession ID GSE53962.

  13. Lucky Motifs in Chinese Folk Art: Interpreting Paper-cut from Chinese Shaanxi

    OpenAIRE

    Xuxiao WANG

    2013-01-01

    Paper-cut is not simply a form of traditional Chinese folk art. Lucky motifs developed in paper-cut certainly acquired profound cultural connotations. As paper-cut is a time-honoured skill across the nation, interpreting those motifs requires cultural receptiveness and anthropological sensitivity. The author of this article analyzes examples of paper-cut from Northern Shaanxi, China, to identify the cohesive motifs and explore the auspiciousness of the specific concepts of Fu, Lu, Shou, Xi. T...

  14. Universal emergence of PageRank

    Energy Technology Data Exchange (ETDEWEB)

    Frahm, K M; Georgeot, B; Shepelyansky, D L, E-mail: frahm@irsamc.ups-tlse.fr, E-mail: georgeot@irsamc.ups-tlse.fr, E-mail: dima@irsamc.ups-tlse.fr [Laboratoire de Physique Theorique du CNRS, IRSAMC, Universite de Toulouse, UPS, 31062 Toulouse (France)

    2011-11-18

    The PageRank algorithm enables us to rank the nodes of a network through a specific eigenvector of the Google matrix, using a damping parameter {alpha} Element-Of ]0, 1[. Using extensive numerical simulations of large web networks, with a special accent on British University networks, we determine numerically and analytically the universal features of the PageRank vector at its emergence when {alpha} {yields} 1. The whole network can be divided into a core part and a group of invariant subspaces. For {alpha} {yields} 1, PageRank converges to a universal power-law distribution on the invariant subspaces whose size distribution also follows a universal power law. The convergence of PageRank at {alpha} {yields} 1 is controlled by eigenvalues of the core part of the Google matrix, which are extremely close to unity, leading to large relaxation times as, for example, in spin glasses. (paper)

  15. Universal emergence of PageRank

    International Nuclear Information System (INIS)

    Frahm, K M; Georgeot, B; Shepelyansky, D L

    2011-01-01

    The PageRank algorithm enables us to rank the nodes of a network through a specific eigenvector of the Google matrix, using a damping parameter α ∈ ]0, 1[. Using extensive numerical simulations of large web networks, with a special accent on British University networks, we determine numerically and analytically the universal features of the PageRank vector at its emergence when α → 1. The whole network can be divided into a core part and a group of invariant subspaces. For α → 1, PageRank converges to a universal power-law distribution on the invariant subspaces whose size distribution also follows a universal power law. The convergence of PageRank at α → 1 is controlled by eigenvalues of the core part of the Google matrix, which are extremely close to unity, leading to large relaxation times as, for example, in spin glasses. (paper)

  16. MOMFER: A Search Engine of Thompson's Motif-Index of Folk Literature

    NARCIS (Netherlands)

    Karsdorp, F.B.; van der Meulen, Marten; Meder, Theo; van den Bosch, Antal

    2015-01-01

    More than fifty years after the first edition of Thompson's seminal Motif-Indexof Folk Literature, we present an online search engine tailored to fully disclose the index digitally. This search engine, called MOMFER, greatly enhances the searchability of the Motif-Index and provides exciting new

  17. Identifying and ranking implicit leadership strategies to promote evidence-based practice implementation in addiction health services.

    Science.gov (United States)

    Guerrero, Erick G; Padwa, Howard; Fenwick, Karissa; Harris, Lesley M; Aarons, Gregory A

    2016-05-14

    Despite a solid research base supporting evidence-based practices (EBPs) for addiction treatment such as contingency management and medication-assisted treatment, these services are rarely implemented and delivered in community-based addiction treatment programs in the USA. As a result, many clients do not benefit from the most current and efficacious treatments, resulting in reduced quality of care and compromised treatment outcomes. Previous research indicates that addiction program leaders play a key role in supporting EBP adoption and use. The present study expanded on this previous work to identify strategies that addiction treatment program leaders report using to implement new practices. We relied on a staged and iterative mixed-methods approach to achieve the following four goals: (a) collect data using focus groups and semistructured interviews and conduct analyses to identify implicit managerial strategies for implementation, (b) use surveys to quantitatively rank strategy effectiveness, (c) determine how strategies fit with existing theories of organizational management and change, and (d) use a consensus group to corroborate and expand on the results of the previous three stages. Each goal corresponded to a methodological phase, which included data collection and analytic approaches to identify and evaluate leadership interventions that facilitate EBP implementation in community-based addiction treatment programs. Findings show that the top-ranked strategies involved the recruitment and selection of staff members receptive to change, offering support and requesting feedback during the implementation process, and offering in vivo and hands-on training. Most strategies corresponded to emergent implementation leadership approaches that also utilize principles of transformational and transactional leadership styles. Leadership behaviors represented orientations such as being proactive to respond to implementation needs, supportive to assist staff members

  18. Effects of microwave irradiation treatment on physicochemical characteristics of Chinese low-rank coals

    International Nuclear Information System (INIS)

    Ge, Lichao; Zhang, Yanwei; Wang, Zhihua; Zhou, Junhu; Cen, Kefa

    2013-01-01

    Highlights: • Typical Chinese lignites with various ranks are upgraded through microwave. • The pore distribution extends to micropore region, BET area and volume increase. • FTIR show the change of microstructure and improvement in coal rank after upgrading. • Upgraded coals exhibit weak combustion similar to Da Tong bituminous coal. • More evident effects are obtained for raw brown coal with relative lower rank. - Abstract: This study investigates the effects of microwave irradiation treatment on coal composition, pore structure, coal rank, function groups, and combustion characteristics of typical Chinese low-rank coals. Results showed that the upgrading process (microwave irradiation treatment) significantly reduced the coals’ inherent moisture, and increased their calorific value and fixed carbon content. It was also found that the upgrading process generated micropores and increased pore volume and surface area of the coals. Results on the oxygen/carbon ratio parameter indicated that the low-rank coals were upgraded to high-rank coals after the upgrading process, which is in agreement with the findings from Fourier transform infrared spectroscopy. Unstable components in the coal were converted into stable components during the upgrading process. Thermo-gravimetric analysis showed that the combustion processes of upgraded coals were delayed toward the high-temperature region, the ignition and burnout temperatures increased, and the comprehensive combustion parameter decreased. Compared with raw brown coals, the upgraded coals exhibited weak combustion characteristics similar to bituminous coal. The changes in physicochemical characteristics became more notable when processing temperature increased from 130 °C to 160 °C or the rank of raw brown coal was lower. Microwave irradiation treatment could be considered as an effective dewatering and upgrading process

  19. Low-rank extremal positive-partial-transpose states and unextendible product bases

    International Nuclear Information System (INIS)

    Leinaas, Jon Magne; Sollid, Per Oyvind; Myrheim, Jan

    2010-01-01

    It is known how to construct, in a bipartite quantum system, a unique low-rank entangled mixed state with positive partial transpose (a PPT state) from an unextendible product basis (UPB), defined as an unextendible set of orthogonal product vectors. We point out that a state constructed in this way belongs to a continuous family of entangled PPT states of the same rank, all related by nonsingular unitary or nonunitary product transformations. The characteristic property of a state ρ in such a family is that its kernel Ker ρ has a generalized UPB, a basis of product vectors, not necessarily orthogonal, with no product vector in Im ρ, the orthogonal complement of Ker ρ. The generalized UPB in Ker ρ has the special property that it can be transformed to orthogonal form by a product transformation. In the case of a system of dimension 3x3, we give a complete parametrization of orthogonal UPBs. This is then a parametrization of families of rank 4 entangled (and extremal) PPT states, and we present strong numerical evidence that it is a complete classification of such states. We speculate that the lowest rank entangled and extremal PPT states also in higher dimensions are related to generalized, nonorthogonal UPBs in similar ways.

  20. A Genetic Programming Method for the Identification of Signal Peptides and Prediction of Their Cleavage Sites

    Directory of Open Access Journals (Sweden)

    David Lennartsson

    2004-01-01

    Full Text Available A novel approach to signal peptide identification is presented. We use an evolutionary algorithm for automatic evolution of classification programs, so-called programmatic motifs. The variant of evolutionary algorithm used is called genetic programming where a population of solution candidates in the form of full computer programs is evolved, based on training examples consisting of signal peptide sequences. The method is compared with a previous work using artificial neural network (ANN approaches. Some advantages compared to ANNs are noted. The programmatic motif can perform computational tasks beyond that of feed-forward neural networks and has also other advantages such as readability. The best motif evolved was analyzed and shown to detect the h-region of the signal peptide. A powerful parallel computer cluster was used for the experiment.

  1. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: Identification of an RGFRRR motif governing fungal cell entry

    Energy Technology Data Exchange (ETDEWEB)

    Sagaram, Uma S.; El-Mounadi, Kaoutar; Buchko, Garry W.; Berg, Howard R.; Kaur, Jagdeep; Pandurangi, Raghoottama; Smith, Thomas J.; Shah, Dilip

    2013-12-04

    A highly conserved plant defensin MtDef4 potently inhibits the growth of a filamentous fungus Fusarium graminearum. MtDef4 is internalized by cells of F. graminearum. To determine its mechanism of fungal cell entry and antifungal action, NMR solution structure of MtDef4 has been determined. The analysis of its structure has revealed a positively charged patch on the surface of the protein consisting of arginine residues in its γ-core signature, a major determinant of the antifungal activity of MtDef4. Here, we report functional analysis of the RGFRRR motif of the γ-core signature of MtDef4. The replacement of RGFRRR to AAAARR or to RGFRAA not only abolishes fungal cell entry but also results in loss of the antifungal activity of MtDef4. MtDef4 binds strongly to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Mutations of RGFRRR which abolish fungal cell entry of MtDef4 also impair its binding to PA. Our results suggest that RGFRRR motif is a translocation signal for entry of MtDef4 into fungal cells and that this positively charged motif likely mediates interaction of this defensin with PA as part of its antifungal action.

  2. A Ranking Approach to Genomic Selection.

    Science.gov (United States)

    Blondel, Mathieu; Onogi, Akio; Iwata, Hiroyoshi; Ueda, Naonori

    2015-01-01

    Genomic selection (GS) is a recent selective breeding method which uses predictive models based on whole-genome molecular markers. Until now, existing studies formulated GS as the problem of modeling an individual's breeding value for a particular trait of interest, i.e., as a regression problem. To assess predictive accuracy of the model, the Pearson correlation between observed and predicted trait values was used. In this paper, we propose to formulate GS as the problem of ranking individuals according to their breeding value. Our proposed framework allows us to employ machine learning methods for ranking which had previously not been considered in the GS literature. To assess ranking accuracy of a model, we introduce a new measure originating from the information retrieval literature called normalized discounted cumulative gain (NDCG). NDCG rewards more strongly models which assign a high rank to individuals with high breeding value. Therefore, NDCG reflects a prerequisite objective in selective breeding: accurate selection of individuals with high breeding value. We conducted a comparison of 10 existing regression methods and 3 new ranking methods on 6 datasets, consisting of 4 plant species and 25 traits. Our experimental results suggest that tree-based ensemble methods including McRank, Random Forests and Gradient Boosting Regression Trees achieve excellent ranking accuracy. RKHS regression and RankSVM also achieve good accuracy when used with an RBF kernel. Traditional regression methods such as Bayesian lasso, wBSR and BayesC were found less suitable for ranking. Pearson correlation was found to correlate poorly with NDCG. Our study suggests two important messages. First, ranking methods are a promising research direction in GS. Second, NDCG can be a useful evaluation measure for GS.

  3. BayesMD: flexible biological modeling for motif discovery

    DEFF Research Database (Denmark)

    Tang, Man-Hung Eric; Krogh, Anders; Winther, Ole

    2008-01-01

    We present BayesMD, a Bayesian Motif Discovery model with several new features. Three different types of biological a priori knowledge are built into the framework in a modular fashion. A mixture of Dirichlets is used as prior over nucleotide probabilities in binding sites. It is trained on trans......We present BayesMD, a Bayesian Motif Discovery model with several new features. Three different types of biological a priori knowledge are built into the framework in a modular fashion. A mixture of Dirichlets is used as prior over nucleotide probabilities in binding sites. It is trained...

  4. Dynamic Matrix Rank

    DEFF Research Database (Denmark)

    Frandsen, Gudmund Skovbjerg; Frandsen, Peter Frands

    2009-01-01

    We consider maintaining information about the rank of a matrix under changes of the entries. For n×n matrices, we show an upper bound of O(n1.575) arithmetic operations and a lower bound of Ω(n) arithmetic operations per element change. The upper bound is valid when changing up to O(n0.575) entries...... in a single column of the matrix. We also give an algorithm that maintains the rank using O(n2) arithmetic operations per rank one update. These bounds appear to be the first nontrivial bounds for the problem. The upper bounds are valid for arbitrary fields, whereas the lower bound is valid for algebraically...... closed fields. The upper bound for element updates uses fast rectangular matrix multiplication, and the lower bound involves further development of an earlier technique for proving lower bounds for dynamic computation of rational functions....

  5. Lucky Motifs in Chinese Folk Art: Interpreting Paper-cut from Chinese Shaanxi

    Directory of Open Access Journals (Sweden)

    Xuxiao WANG

    2013-11-01

    Full Text Available Paper-cut is not simply a form of traditional Chinese folk art. Lucky motifs developed in paper-cut certainly acquired profound cultural connotations. As paper-cut is a time-honoured skill across the nation, interpreting those motifs requires cultural receptiveness and anthropological sensitivity. The author of this article analyzes examples of paper-cut from Northern Shaanxi, China, to identify the cohesive motifs and explore the auspiciousness of the specific concepts of Fu, Lu, Shou, Xi. The paper-cut of Northern Shaanxi is an ideal representative of the craft as a whole because of the relative stability of this region in history, in terms of both art and culture. Furthermore, its straightforward style provides a clear demonstration of motifs regarding folk understanding of expectations for life.

  6. Statistical methods for ranking data

    CERN Document Server

    Alvo, Mayer

    2014-01-01

    This book introduces advanced undergraduate, graduate students and practitioners to statistical methods for ranking data. An important aspect of nonparametric statistics is oriented towards the use of ranking data. Rank correlation is defined through the notion of distance functions and the notion of compatibility is introduced to deal with incomplete data. Ranking data are also modeled using a variety of modern tools such as CART, MCMC, EM algorithm and factor analysis. This book deals with statistical methods used for analyzing such data and provides a novel and unifying approach for hypotheses testing. The techniques described in the book are illustrated with examples and the statistical software is provided on the authors’ website.

  7. Hitting the Rankings Jackpot

    Science.gov (United States)

    Chapman, David W.

    2008-01-01

    Recently, Samford University was ranked 27th in the nation in a report released by "Forbes" magazine. In this article, the author relates how the people working at Samford University were surprised at its ranking. Although Samford is the largest privately institution in Alabama, its distinguished academic achievements aren't even…

  8. Influence of the hydrothermal dewatering on the combustion characteristics of Chinese low-rank coals

    International Nuclear Information System (INIS)

    Ge, Lichao; Zhang, Yanwei; Xu, Chang; Wang, Zhihua; Zhou, Junhu; Cen, Kefa

    2015-01-01

    This study investigates the influence of hydrothermal dewatering performed at different temperatures on the combustion characteristics of Chinese low-rank coals with different coalification maturities. It was found that the upgrading process significantly decreased the inherent moisture and oxygen content, increased the calorific value and fixed carbon content, and promoted the damage of the hydrophilic oxygen functional groups. The results of oxygen/carbon atomic ratio indicated that the upgrading process converted the low-rank coals near to high-rank coals which can also be gained using the Fourier transform infrared spectroscopy. The thermogravimetric analysis showed that the combustion processes of upgraded coals were delayed toward the high temperature region, and the upgraded coals had higher ignition and burnout temperature. On the other hand, based on the higher average combustion rate and comprehensive combustion parameter, the upgraded coals performed better compared with raw brown coals and the Da Tong bituminous coal. In ignition segment, the activation energy increased after treatment but decreased in the combustion stage. The changes in coal compositions, microstructure, rank, and combustion characteristics were more notable as the temperature in hydrothermal dewatering increased from 250 to 300 °C or coals of lower ranks were used. - Highlights: • Typical Chinese lignites with various ranks are upgraded by hydrothermal dewatering. • Upgraded coals exhibit chemical compositions comparable with that of bituminous coal. • FTIR show the change of microstructure and improvement in coal rank after upgrading. • Upgraded coals exhibit difficulty in ignition but combust easily. • More evident effects are obtained for raw brown coal with relative lower rank.

  9. A peptide affinity column for the identification of integrin alpha IIb-binding proteins.

    Science.gov (United States)

    Daxecker, Heide; Raab, Markus; Bernard, Elise; Devocelle, Marc; Treumann, Achim; Moran, Niamh

    2008-03-01

    To understand the regulation of integrin alpha(IIb)beta(3), a critical platelet adhesion molecule, we have developed a peptide affinity chromatography method using the known integrin regulatory motif, LAMWKVGFFKR. Using standard Fmoc chemistry, this peptide was synthesized onto a Toyopearl AF-Amino-650 M resin on a 6-aminohexanoic acid (Ahx) linker. Peptide density was controlled by acetylation of 83% of the Ahx amino groups. Four recombinant human proteins (CIB1, PP1, ICln and RN181), previously identified as binding to this integrin regulatory motif, were specifically retained by the column containing the integrin peptide but not by a column presenting an irrelevant peptide. Hemoglobin, creatine kinase, bovine serum albumin, fibrinogen and alpha-tubulin failed to bind under the chosen conditions. Immunodetection methods confirmed the binding of endogenous platelet proteins, including CIB1, PP1, ICln RN181, AUP-1 and beta3-integrin, from a detergent-free platelet lysate. Thus, we describe a reproducible method that facilitates the reliable extraction of specific integrin-binding proteins from complex biological matrices. This methodology may enable the sensitive and specific identification of proteins that interact with linear, membrane-proximal peptide motifs such as the integrin regulatory motif LAMWKVGFFKR.

  10. Sequence alignment reveals possible MAPK docking motifs on HIV proteins.

    Directory of Open Access Journals (Sweden)

    Perry Evans

    Full Text Available Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs. MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.

  11. A tilting approach to ranking influence

    KAUST Repository

    Genton, Marc G.

    2014-12-01

    We suggest a new approach, which is applicable for general statistics computed from random samples of univariate or vector-valued or functional data, to assessing the influence that individual data have on the value of a statistic, and to ranking the data in terms of that influence. Our method is based on, first, perturbing the value of the statistic by ‘tilting’, or reweighting, each data value, where the total amount of tilt is constrained to be the least possible, subject to achieving a given small perturbation of the statistic, and, then, taking the ranking of the influence of data values to be that which corresponds to ranking the changes in data weights. It is shown, both theoretically and numerically, that this ranking does not depend on the size of the perturbation, provided that the perturbation is sufficiently small. That simple result leads directly to an elegant geometric interpretation of the ranks; they are the ranks of the lengths of projections of the weights onto a ‘line’ determined by the first empirical principal component function in a generalized measure of covariance. To illustrate the generality of the method we introduce and explore it in the case of functional data, where (for example) it leads to generalized boxplots. The method has the advantage of providing an interpretable ranking that depends on the statistic under consideration. For example, the ranking of data, in terms of their influence on the value of a statistic, is different for a measure of location and for a measure of scale. This is as it should be; a ranking of data in terms of their influence should depend on the manner in which the data are used. Additionally, the ranking recognizes, rather than ignores, sign, and in particular can identify left- and right-hand ‘tails’ of the distribution of a random function or vector.

  12. Stochastic Resonance in Neuronal Network Motifs with Ornstein-Uhlenbeck Colored Noise

    Directory of Open Access Journals (Sweden)

    Xuyang Lou

    2014-01-01

    Full Text Available We consider here the effect of the Ornstein-Uhlenbeck colored noise on the stochastic resonance of the feed-forward-loop (FFL network motif. The FFL motif is modeled through the FitzHugh-Nagumo neuron model as well as the chemical coupling. Our results show that the noise intensity and the correlation time of the noise process serve as the control parameters, which have great impacts on the stochastic dynamics of the FFL motif. We find that, with a proper choice of noise intensities and the correlation time of the noise process, the signal-to-noise ratio (SNR can display more than one peak.

  13. Combining evidence and values in priority setting: testing the balance sheet method in a low-income country.

    Science.gov (United States)

    Makundi, Emmanuel; Kapiriri, Lydia; Norheim, Ole Frithjof

    2007-09-24

    Procedures for priority setting need to incorporate both scientific evidence and public values. The aim of this study was to test out a model for priority setting which incorporates both scientific evidence and public values, and to explore use of evidence by a selection of stakeholders and to study reasons for the relative ranking of health care interventions in a setting of extreme resource scarcity. Systematic search for and assessment of relevant evidence for priority setting in a low-income country. Development of a balance sheet according to Eddy's explicit method. Eight group interviews (n-85), using a modified nominal group technique for eliciting individual and group rankings of a given set of health interventions. The study procedure made it possible to compare the groups' ranking before and after all the evidence was provided to participants. A rank deviation is significant if the rank order of the same intervention differed by two or more points on the ordinal scale. A comparison between the initial rank and the final rank (before deliberation) showed a rank deviation of 67%. The difference between the initial rank and the final rank after discussion and voting gave a rank deviation of 78%. Evidence-based and deliberative decision-making does change priorities significantly in an experimental setting. Our use of the balance sheet method was meant as a demonstration project, but could if properly developed be feasible for health planners, experts and health workers, although more work is needed before it can be used for laypersons.

  14. Gene Isolation Using Degenerate Primers Targeting Protein Motif: A Laboratory Exercise

    Science.gov (United States)

    Yeo, Brandon Pei Hui; Foong, Lian Chee; Tam, Sheh May; Lee, Vivian; Hwang, Siaw San

    2018-01-01

    Structures and functions of protein motifs are widely included in many biology-based course syllabi. However, little emphasis is placed to link this knowledge to applications in biotechnology to enhance the learning experience. Here, the conserved motifs of nucleotide binding site-leucine rich repeats (NBS-LRR) proteins, successfully used for the…

  15. Wayward Warriors: The Viking Motif in Swedish and English Children's Literature

    Science.gov (United States)

    Sundmark, Björn

    2014-01-01

    In this article the Viking motif in children's literature is explored--from its roots in (adult) nationalist and antiquarian discourse, over pedagogical and historical texts for children, to the eventual diversification (or dissolution) of the motif into different genres and forms. The focus is on Swedish Viking narratives, but points of…

  16. Improving the use of research evidence in guideline development: 6. Determining which outcomes are important

    Directory of Open Access Journals (Sweden)

    Fretheim Atle

    2006-12-01

    Full Text Available Abstract Background The World Health Organization (WHO, like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the sixth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives We reviewed the literature on determining which outcomes are important for the development of guidelines. Methods We searched five databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct a complete systematic review ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers We did not find a systematic review that addresses any of the following key questions and we found limited relevant research evidence. What methods should WHO use to identify important outcomes? • Methods of outcome identification should be transparent and explicit. • The consultation process should start with identification of all relevant outcomes associated with an intervention. • Those affected, including consumers, should be involved in the selection of outcomes. • A question driven approach (what is important? is preferable to a data driven approach (what data are at hand? to identify important outcomes. What type of outcomes should WHO consider and how should cultural diversity be taken account of in the selection of outcomes? • Desirable (benefits, less burden and savings and undesirable effects should be considered in all guidelines. • Undesirable effects include harms (including the possibility of unanticipated adverse effects, greater burden (e.g. having to go to the doctor and costs (including opportunity costs. • Important outcomes (e

  17. Identification and ranking of the risk factors of cloud computing in State-Owned organizations

    Directory of Open Access Journals (Sweden)

    Noor Mohammad Yaghoubi

    2015-05-01

    Full Text Available Rapid development of processing and storage technologies and the success of the Internet have made computing resources cheaper, more powerful and more available than before. This technological trend has enabled the realization of a new computing model called cloud computing. Recently, the State-Owned organizations have begun to utilize cloud computing architectures, platforms, and applications to deliver services and meet constituents’ needs. Despite all of the advantages and opportunities of cloud computing technology, there are so many risks that State-Owned organizations need to know about before their migration to cloud environment. The purpose of this study is to identify and rank the risks factors of cloud computing in State-Owned organizations by making use of IT experts’ opinion. Firstly, by reviewing key articles, a comprehensive list of risks factors were extracted and classified into two categories: tangible and intangible. Then, six experts were interviewed about these risks and their classifications, and 10 risks were identified. After that, process of ranking the risks was done by seeking help from 52 experts and by fuzzy analytic hierarchy process. The results show that experts have identified intangible risks as the most important risks in cloud computing usage by State-Owned organizations. As the results indicate, "data confidentiality" risk has the highest place among the other risks.

  18. Ranking adverse drug reactions with crowdsourcing.

    Science.gov (United States)

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel; Altman, Russ B

    2015-03-23

    There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. The intent of the study was to rank ADRs according to severity. We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.

  19. Ranking Adverse Drug Reactions With Crowdsourcing

    KAUST Repository

    Gottlieb, Assaf

    2015-03-23

    Background: There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective: The intent of the study was to rank ADRs according to severity. Methods: We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results: There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions: ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.

  20. Ranking scientific publications: the effect of nonlinearity

    Science.gov (United States)

    Yao, Liyang; Wei, Tian; Zeng, An; Fan, Ying; di, Zengru

    2014-10-01

    Ranking the significance of scientific publications is a long-standing challenge. The network-based analysis is a natural and common approach for evaluating the scientific credit of papers. Although the number of citations has been widely used as a metric to rank papers, recently some iterative processes such as the well-known PageRank algorithm have been applied to the citation networks to address this problem. In this paper, we introduce nonlinearity to the PageRank algorithm when aggregating resources from different nodes to further enhance the effect of important papers. The validation of our method is performed on the data of American Physical Society (APS) journals. The results indicate that the nonlinearity improves the performance of the PageRank algorithm in terms of ranking effectiveness, as well as robustness against malicious manipulations. Although the nonlinearity analysis is based on the PageRank algorithm, it can be easily extended to other iterative ranking algorithms and similar improvements are expected.

  1. Ranking scientific publications: the effect of nonlinearity.

    Science.gov (United States)

    Yao, Liyang; Wei, Tian; Zeng, An; Fan, Ying; Di, Zengru

    2014-10-17

    Ranking the significance of scientific publications is a long-standing challenge. The network-based analysis is a natural and common approach for evaluating the scientific credit of papers. Although the number of citations has been widely used as a metric to rank papers, recently some iterative processes such as the well-known PageRank algorithm have been applied to the citation networks to address this problem. In this paper, we introduce nonlinearity to the PageRank algorithm when aggregating resources from different nodes to further enhance the effect of important papers. The validation of our method is performed on the data of American Physical Society (APS) journals. The results indicate that the nonlinearity improves the performance of the PageRank algorithm in terms of ranking effectiveness, as well as robustness against malicious manipulations. Although the nonlinearity analysis is based on the PageRank algorithm, it can be easily extended to other iterative ranking algorithms and similar improvements are expected.

  2. Statistical Optimality in Multipartite Ranking and Ordinal Regression.

    Science.gov (United States)

    Uematsu, Kazuki; Lee, Yoonkyung

    2015-05-01

    Statistical optimality in multipartite ranking is investigated as an extension of bipartite ranking. We consider the optimality of ranking algorithms through minimization of the theoretical risk which combines pairwise ranking errors of ordinal categories with differential ranking costs. The extension shows that for a certain class of convex loss functions including exponential loss, the optimal ranking function can be represented as a ratio of weighted conditional probability of upper categories to lower categories, where the weights are given by the misranking costs. This result also bridges traditional ranking methods such as proportional odds model in statistics with various ranking algorithms in machine learning. Further, the analysis of multipartite ranking with different costs provides a new perspective on non-smooth list-wise ranking measures such as the discounted cumulative gain and preference learning. We illustrate our findings with simulation study and real data analysis.

  3. Country-specific determinants of world university rankings.

    Science.gov (United States)

    Pietrucha, Jacek

    2018-01-01

    This paper examines country-specific factors that affect the three most influential world university rankings (the Academic Ranking of World Universities, the QS World University Ranking, and the Times Higher Education World University Ranking). We run a cross sectional regression that covers 42-71 countries (depending on the ranking and data availability). We show that the position of universities from a country in the ranking is determined by the following country-specific variables: economic potential of the country, research and development expenditure, long-term political stability (freedom from war, occupation, coups and major changes in the political system), and institutional variables, including government effectiveness.

  4. Identification and characterisation of the angiotensin converting enzyme-3 (ACE3 gene: a novel mammalian homologue of ACE

    Directory of Open Access Journals (Sweden)

    Phelan Anne

    2007-06-01

    Full Text Available Abstract Background Mammalian angiotensin converting enzyme (ACE plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. Conclusion In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.

  5. Finding a Leucine in a Haystack: Searching the Proteome for ambigous Leucine-Aspartic Acid motifs

    KAUST Repository

    Arold, Stefan T.

    2016-01-01

    LDMF predicted 13 new LD motifs in humans. Using biophysical assays, we experimentally confirmed in vitro interactions for four novel LD motif proteins. Thus, LDMF allows proteome-wide discovery of LD motifs, despite a highly ambiguous sequence pattern. Functional implications will be discussed.

  6. Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.

    Science.gov (United States)

    Wang, Xin; Lin, Peijie; Ho, Joshua W K

    2018-01-19

    It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.

  7. Groundwater contaminant plume ranking

    International Nuclear Information System (INIS)

    1988-08-01

    Containment plumes at Uranium Mill Tailings Remedial Action (UMTRA) Project sites were ranked to assist in Subpart B (i.e., restoration requirements of 40 CFR Part 192) compliance strategies for each site, to prioritize aquifer restoration, and to budget future requests and allocations. The rankings roughly estimate hazards to the environment and human health, and thus assist in determining for which sites cleanup, if appropriate, will provide the greatest benefits for funds available. The rankings are based on the scores that were obtained using the US Department of Energy's (DOE) Modified Hazard Ranking System (MHRS). The MHRS and HRS consider and score three hazard modes for a site: migration, fire and explosion, and direct contact. The migration hazard mode score reflects the potential for harm to humans or the environment from migration of a hazardous substance off a site by groundwater, surface water, and air; it is a composite of separate scores for each of these routes. For ranking the containment plumes at UMTRA Project sites, it was assumed that each site had been remediated in compliance with the EPA standards and that relict contaminant plumes were present. Therefore, only the groundwater route was scored, and the surface water and air routes were not considered. Section 2.0 of this document describes the assumptions and procedures used to score the groundwater route, and Section 3.0 provides the resulting scores for each site. 40 tabs

  8. POWRS: position-sensitive motif discovery.

    Directory of Open Access Journals (Sweden)

    Ian W Davis

    Full Text Available Transcription factors and the short, often degenerate DNA sequences they recognize are central regulators of gene expression, but their regulatory code is challenging to dissect experimentally. Thus, computational approaches have long been used to identify putative regulatory elements from the patterns in promoter sequences. Here we present a new algorithm "POWRS" (POsition-sensitive WoRd Set for identifying regulatory sequence motifs, specifically developed to address two common shortcomings of existing algorithms. First, POWRS uses the position-specific enrichment of regulatory elements near transcription start sites to significantly increase sensitivity, while providing new information about the preferred localization of those elements. Second, POWRS forgoes position weight matrices for a discrete motif representation that appears more resistant to over-generalization. We apply this algorithm to discover sequences related to constitutive, high-level gene expression in the model plant Arabidopsis thaliana, and then experimentally validate the importance of those elements by systematically mutating two endogenous promoters and measuring the effect on gene expression levels. This provides a foundation for future efforts to rationally engineer gene expression in plants, a problem of great importance in developing biotech crop varieties.BSD-licensed Python code at http://grassrootsbio.com/papers/powrs/.

  9. Poly(A) motif prediction using spectral latent features from human DNA sequences

    KAUST Repository

    Xie, Bo; Jankovic, Boris R.; Bajic, Vladimir B.; Song, Le; Gao, Xin

    2013-01-01

    Motivation: Polyadenylation is the addition of a poly(A) tail to an RNA molecule. Identifying DNA sequence motifs that signal the addition of poly(A) tails is essential to improved genome annotation and better understanding of the regulatory mechanisms and stability of mRNA.Existing poly(A) motif predictors demonstrate that information extracted from the surrounding nucleotide sequences of candidate poly(A) motifs can differentiate true motifs from the false ones to a great extent. A variety of sophisticated features has been explored, including sequential, structural, statistical, thermodynamic and evolutionary properties. However, most of these methods involve extensive manual feature engineering, which can be time-consuming and can require in-depth domain knowledge.Results: We propose a novel machine-learning method for poly(A) motif prediction by marrying generative learning (hidden Markov models) and discriminative learning (support vector machines). Generative learning provides a rich palette on which the uncertainty and diversity of sequence information can be handled, while discriminative learning allows the performance of the classification task to be directly optimized. Here, we used hidden Markov models for fitting the DNA sequence dynamics, and developed an efficient spectral algorithm for extracting latent variable information from these models. These spectral latent features were then fed into support vector machines to fine-tune the classification performance.We evaluated our proposed method on a comprehensive human poly(A) dataset that consists of 14 740 samples from 12 of the most abundant variants of human poly(A) motifs. Compared with one of the previous state-of-the-art methods in the literature (the random forest model with expert-crafted features), our method reduces the average error rate, false-negative rate and false-positive rate by 26, 15 and 35%, respectively. Meanwhile, our method makes ?30% fewer error predictions relative to the other

  10. Poly(A) motif prediction using spectral latent features from human DNA sequences

    KAUST Repository

    Xie, Bo

    2013-06-21

    Motivation: Polyadenylation is the addition of a poly(A) tail to an RNA molecule. Identifying DNA sequence motifs that signal the addition of poly(A) tails is essential to improved genome annotation and better understanding of the regulatory mechanisms and stability of mRNA.Existing poly(A) motif predictors demonstrate that information extracted from the surrounding nucleotide sequences of candidate poly(A) motifs can differentiate true motifs from the false ones to a great extent. A variety of sophisticated features has been explored, including sequential, structural, statistical, thermodynamic and evolutionary properties. However, most of these methods involve extensive manual feature engineering, which can be time-consuming and can require in-depth domain knowledge.Results: We propose a novel machine-learning method for poly(A) motif prediction by marrying generative learning (hidden Markov models) and discriminative learning (support vector machines). Generative learning provides a rich palette on which the uncertainty and diversity of sequence information can be handled, while discriminative learning allows the performance of the classification task to be directly optimized. Here, we used hidden Markov models for fitting the DNA sequence dynamics, and developed an efficient spectral algorithm for extracting latent variable information from these models. These spectral latent features were then fed into support vector machines to fine-tune the classification performance.We evaluated our proposed method on a comprehensive human poly(A) dataset that consists of 14 740 samples from 12 of the most abundant variants of human poly(A) motifs. Compared with one of the previous state-of-the-art methods in the literature (the random forest model with expert-crafted features), our method reduces the average error rate, false-negative rate and false-positive rate by 26, 15 and 35%, respectively. Meanwhile, our method makes ?30% fewer error predictions relative to the other

  11. Inhibition of osteoclastogenesis by RNA interference targeting RANK

    Directory of Open Access Journals (Sweden)

    Ma Ruofan

    2012-08-01

    Full Text Available Abstract Background Osteoclasts and osteoblasts regulate bone resorption and formation to allow bone remodeling and homeostasis. The balance between bone resorption and formation is disturbed by abnormal recruitment of osteoclasts. Osteoclast differentiation is dependent on the receptor activator of nuclear factor NF-kappa B (RANK ligand (RANKL as well as the macrophage colony-stimulating factor (M-CSF. The RANKL/RANK system and RANK signaling induce osteoclast formation mediated by various cytokines. The RANK/RANKL pathway has been primarily implicated in metabolic, degenerative and neoplastic bone disorders or osteolysis. The central role of RANK/RANKL interaction in osteoclastogenesis makes RANK an attractive target for potential therapies in treatment of osteolysis. The purpose of this study was to assess the effect of inhibition of RANK expression in mouse bone marrow macrophages on osteoclast differentiation and bone resorption. Methods Three pairs of short hairpin RNAs (shRNA targeting RANK were designed and synthesized. The optimal shRNA was selected among three pairs of shRNAs by RANK expression analyzed by Western blot and Real-time PCR. We investigated suppression of osteoclastogenesis of mouse bone marrow macrophages (BMMs using the optimal shRNA by targeting RANK. Results Among the three shRANKs examined, shRANK-3 significantly suppressed [88.3%] the RANK expression (p Conclusions These findings suggest that retrovirus-mediated shRNA targeting RANK inhibits osteoclast differentiation and osteolysis. It may appear an attractive target for preventing osteolysis in humans with a potential clinical application.

  12. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    NARCIS (Netherlands)

    Gibbs, S.; Corsini, E.; Spiekstra, S.W.; Galbiati, V.; Fuchs, H.W.; Degeorge, G.; Troese, M.; Hayden, P.; Deng, W.; Roggen, E.

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low

  13. On Rank and Nullity

    Science.gov (United States)

    Dobbs, David E.

    2012-01-01

    This note explains how Emil Artin's proof that row rank equals column rank for a matrix with entries in a field leads naturally to the formula for the nullity of a matrix and also to an algorithm for solving any system of linear equations in any number of variables. This material could be used in any course on matrix theory or linear algebra.

  14. Ranking economic history journals

    DEFF Research Database (Denmark)

    Di Vaio, Gianfranco; Weisdorf, Jacob Louis

    2010-01-01

    This study ranks-for the first time-12 international academic journals that have economic history as their main topic. The ranking is based on data collected for the year 2007. Journals are ranked using standard citation analysis where we adjust for age, size and self-citation of journals. We also...... compare the leading economic history journals with the leading journals in economics in order to measure the influence on economics of economic history, and vice versa. With a few exceptions, our results confirm the general idea about what economic history journals are the most influential for economic...... history, and that, although economic history is quite independent from economics as a whole, knowledge exchange between the two fields is indeed going on....

  15. Ranking Economic History Journals

    DEFF Research Database (Denmark)

    Di Vaio, Gianfranco; Weisdorf, Jacob Louis

    This study ranks - for the first time - 12 international academic journals that have economic history as their main topic. The ranking is based on data collected for the year 2007. Journals are ranked using standard citation analysis where we adjust for age, size and self-citation of journals. We...... also compare the leading economic history journals with the leading journals in economics in order to measure the influence on economics of economic history, and vice versa. With a few exceptions, our results confirm the general idea about what economic history journals are the most influential...... for economic history, and that, although economic history is quite independent from economics as a whole, knowledge exchange between the two fields is indeed going on....

  16. A Universal Rank-Size Law

    Science.gov (United States)

    2016-01-01

    A mere hyperbolic law, like the Zipf’s law power function, is often inadequate to describe rank-size relationships. An alternative theoretical distribution is proposed based on theoretical physics arguments starting from the Yule-Simon distribution. A modeling is proposed leading to a universal form. A theoretical suggestion for the “best (or optimal) distribution”, is provided through an entropy argument. The ranking of areas through the number of cities in various countries and some sport competition ranking serves for the present illustrations. PMID:27812192

  17. Novel Strategy for Discrimination of Transcription Factor Binding Motifs Employing Mathematical Neural Network

    Science.gov (United States)

    Sugimoto, Asuka; Sumi, Takuya; Kang, Jiyoung; Tateno, Masaru

    2017-07-01

    Recognition in biological macromolecular systems, such as DNA-protein recognition, is one of the most crucial problems to solve toward understanding the fundamental mechanisms of various biological processes. Since specific base sequences of genome DNA are discriminated by proteins, such as transcription factors (TFs), finding TF binding motifs (TFBMs) in whole genome DNA sequences is currently a central issue in interdisciplinary biophysical and information sciences. In the present study, a novel strategy to create a discriminant function for discrimination of TFBMs by constituting mathematical neural networks (NNs) is proposed, together with a method to determine the boundary of signals (TFBMs) and noise in the NN-score (output) space. This analysis also leads to the mathematical limitation of discrimination in the recognition of features representing TFBMs, in an information geometrical manifold. Thus, the present strategy enables the identification of the whole space of TFBMs, right up to the noise boundary.

  18. Discriminative Motif Discovery via Simulated Evolution and Random Under-Sampling

    OpenAIRE

    Song, Tao; Gu, Hong

    2014-01-01

    Conserved motifs in biological sequences are closely related to their structure and functions. Recently, discriminative motif discovery methods have attracted more and more attention. However, little attention has been devoted to the data imbalance problem, which is one of the main reasons affecting the performance of the discriminative models. In this article, a simulated evolution method is applied to solve the multi-class imbalance problem at the stage of data preprocessing, and at the sta...

  19. On the ranking of chemicals based on their PBT characteristics: comparison of different ranking methodologies using selected POPs as an illustrative example.

    Science.gov (United States)

    Sailaukhanuly, Yerbolat; Zhakupbekova, Arai; Amutova, Farida; Carlsen, Lars

    2013-01-01

    Knowledge of the environmental behavior of chemicals is a fundamental part of the risk assessment process. The present paper discusses various methods of ranking of a series of persistent organic pollutants (POPs) according to the persistence, bioaccumulation and toxicity (PBT) characteristics. Traditionally ranking has been done as an absolute (total) ranking applying various multicriteria data analysis methods like simple additive ranking (SAR) or various utility functions (UFs) based rankings. An attractive alternative to these ranking methodologies appears to be partial order ranking (POR). The present paper compares different ranking methods like SAR, UF and POR. Significant discrepancies between the rankings are noted and it is concluded that partial order ranking, as a method without any pre-assumptions concerning possible relation between the single parameters, appears as the most attractive ranking methodology. In addition to the initial ranking partial order methodology offers a wide variety of analytical tools to elucidate the interplay between the objects to be ranked and the ranking parameters. In the present study is included an analysis of the relative importance of the single P, B and T parameters. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. A novel k-mer set memory (KSM) motif representation improves regulatory variant prediction.

    Science.gov (United States)

    Guo, Yuchun; Tian, Kevin; Zeng, Haoyang; Guo, Xiaoyun; Gifford, David Kenneth

    2018-04-13

    The representation and discovery of transcription factor (TF) sequence binding specificities is critical for understanding gene regulatory networks and interpreting the impact of disease-associated noncoding genetic variants. We present a novel TF binding motif representation, the k -mer set memory (KSM), which consists of a set of aligned k -mers that are overrepresented at TF binding sites, and a new method called KMAC for de novo discovery of KSMs. We find that KSMs more accurately predict in vivo binding sites than position weight matrix (PWM) models and other more complex motif models across a large set of ChIP-seq experiments. Furthermore, KSMs outperform PWMs and more complex motif models in predicting in vitro binding sites. KMAC also identifies correct motifs in more experiments than five state-of-the-art motif discovery methods. In addition, KSM-derived features outperform both PWM and deep learning model derived sequence features in predicting differential regulatory activities of expression quantitative trait loci (eQTL) alleles. Finally, we have applied KMAC to 1600 ENCODE TF ChIP-seq data sets and created a public resource of KSM and PWM motifs. We expect that the KSM representation and KMAC method will be valuable in characterizing TF binding specificities and in interpreting the effects of noncoding genetic variations. © 2018 Guo et al.; Published by Cold Spring Harbor Laboratory Press.

  1. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.

    Science.gov (United States)

    Nolan, Emma; Vaillant, François; Branstetter, Daniel; Pal, Bhupinder; Giner, Göknur; Whitehead, Lachlan; Lok, Sheau W; Mann, Gregory B; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Smyth, Gordon K; Dougall, William C; Visvader, Jane E; Lindeman, Geoffrey J

    2016-08-01

    Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.

  2. GPUmotif: an ultra-fast and energy-efficient motif analysis program using graphics processing units.

    Science.gov (United States)

    Zandevakili, Pooya; Hu, Ming; Qin, Zhaohui

    2012-01-01

    Computational detection of TF binding patterns has become an indispensable tool in functional genomics research. With the rapid advance of new sequencing technologies, large amounts of protein-DNA interaction data have been produced. Analyzing this data can provide substantial insight into the mechanisms of transcriptional regulation. However, the massive amount of sequence data presents daunting challenges. In our previous work, we have developed a novel algorithm called Hybrid Motif Sampler (HMS) that enables more scalable and accurate motif analysis. Despite much improvement, HMS is still time-consuming due to the requirement to calculate matching probabilities position-by-position. Using the NVIDIA CUDA toolkit, we developed a graphics processing unit (GPU)-accelerated motif analysis program named GPUmotif. We proposed a "fragmentation" technique to hide data transfer time between memories. Performance comparison studies showed that commonly-used model-based motif scan and de novo motif finding procedures such as HMS can be dramatically accelerated when running GPUmotif on NVIDIA graphics cards. As a result, energy consumption can also be greatly reduced when running motif analysis using GPUmotif. The GPUmotif program is freely available at http://sourceforge.net/projects/gpumotif/

  3. GPUmotif: an ultra-fast and energy-efficient motif analysis program using graphics processing units.

    Directory of Open Access Journals (Sweden)

    Pooya Zandevakili

    Full Text Available Computational detection of TF binding patterns has become an indispensable tool in functional genomics research. With the rapid advance of new sequencing technologies, large amounts of protein-DNA interaction data have been produced. Analyzing this data can provide substantial insight into the mechanisms of transcriptional regulation. However, the massive amount of sequence data presents daunting challenges. In our previous work, we have developed a novel algorithm called Hybrid Motif Sampler (HMS that enables more scalable and accurate motif analysis. Despite much improvement, HMS is still time-consuming due to the requirement to calculate matching probabilities position-by-position. Using the NVIDIA CUDA toolkit, we developed a graphics processing unit (GPU-accelerated motif analysis program named GPUmotif. We proposed a "fragmentation" technique to hide data transfer time between memories. Performance comparison studies showed that commonly-used model-based motif scan and de novo motif finding procedures such as HMS can be dramatically accelerated when running GPUmotif on NVIDIA graphics cards. As a result, energy consumption can also be greatly reduced when running motif analysis using GPUmotif. The GPUmotif program is freely available at http://sourceforge.net/projects/gpumotif/

  4. Block models and personalized PageRank.

    Science.gov (United States)

    Kloumann, Isabel M; Ugander, Johan; Kleinberg, Jon

    2017-01-03

    Methods for ranking the importance of nodes in a network have a rich history in machine learning and across domains that analyze structured data. Recent work has evaluated these methods through the "seed set expansion problem": given a subset [Formula: see text] of nodes from a community of interest in an underlying graph, can we reliably identify the rest of the community? We start from the observation that the most widely used techniques for this problem, personalized PageRank and heat kernel methods, operate in the space of "landing probabilities" of a random walk rooted at the seed set, ranking nodes according to weighted sums of landing probabilities of different length walks. Both schemes, however, lack an a priori relationship to the seed set objective. In this work, we develop a principled framework for evaluating ranking methods by studying seed set expansion applied to the stochastic block model. We derive the optimal gradient for separating the landing probabilities of two classes in a stochastic block model and find, surprisingly, that under reasonable assumptions the gradient is asymptotically equivalent to personalized PageRank for a specific choice of the PageRank parameter [Formula: see text] that depends on the block model parameters. This connection provides a formal motivation for the success of personalized PageRank in seed set expansion and node ranking generally. We use this connection to propose more advanced techniques incorporating higher moments of landing probabilities; our advanced methods exhibit greatly improved performance, despite being simple linear classification rules, and are even competitive with belief propagation.

  5. Microbiological method for radiation sterilization (II). Identification procedure of gram positive bacteria by using BBL CRYSTAL GP identification kit

    International Nuclear Information System (INIS)

    Koshikawa, Tomihiko

    2004-01-01

    The part II in this title series describes details of the commercially available BBL CRYSTAL GP Identification Kit with the software (Becton, Dickinson and Co., Ltd.), by which identification of Gram positive bacteria as well as their number becoming easier in the radiation sterilization of medical devices. Isolation of a bacterium has to be confirmed by microscopy and its Gram positive property, by the Gram staining. The exponentially growing bacteria are to be inoculated in the Kit and cultured for 18-24 hr at 37 deg C with the lid attached by substrates for identification. Reactions to substrates are to be judged by CRYSTAL auto-reader, which is further to be searched by the computer software (code-book) for final identification. For possible misidentification, re-isolation of the bacterium, prolonged culture, concentrated inoculation and re-consideration for ranking of identification the software provides are necessary as well as other identification approaches. Representative bacteria as the bioburden are spp. of Bacilli, Corynebacteria, Staphylococci and Micrococci. (N.I.)

  6. Comparing classical and quantum PageRanks

    Science.gov (United States)

    Loke, T.; Tang, J. W.; Rodriguez, J.; Small, M.; Wang, J. B.

    2017-01-01

    Following recent developments in quantum PageRanking, we present a comparative analysis of discrete-time and continuous-time quantum-walk-based PageRank algorithms. Relative to classical PageRank and to different extents, the quantum measures better highlight secondary hubs and resolve ranking degeneracy among peripheral nodes for all networks we studied in this paper. For the discrete-time case, we investigated the periodic nature of the walker's probability distribution for a wide range of networks and found that the dominant period does not grow with the size of these networks. Based on this observation, we introduce a new quantum measure using the maximum probabilities of the associated walker during the first couple of periods. This is particularly important, since it leads to a quantum PageRanking scheme that is scalable with respect to network size.

  7. Overlapping ETS and CRE Motifs (G/CCGGAAGTGACGTCA) Preferentially Bound by GABPα and CREB Proteins

    Science.gov (United States)

    Chatterjee, Raghunath; Zhao, Jianfei; He, Ximiao; Shlyakhtenko, Andrey; Mann, Ishminder; Waterfall, Joshua J.; Meltzer, Paul; Sathyanarayana, B. K.; FitzGerald, Peter C.; Vinson, Charles

    2012-01-01

    Previously, we identified 8-bps long DNA sequences (8-mers) that localize in human proximal promoters and grouped them into known transcription factor binding sites (TFBS). We now examine split 8-mers consisting of two 4-mers separated by 1-bp to 30-bps (X4-N1-30-X4) to identify pairs of TFBS that localize in proximal promoters at a precise distance. These include two overlapping TFBS: the ETS⇔ETS motif (C/GCCGGAAGCGGAA) and the ETS⇔CRE motif (C/GCGGAAGTGACGTCAC). The nucleotides in bold are part of both TFBS. Molecular modeling shows that the ETS⇔CRE motif can be bound simultaneously by both the ETS and the B-ZIP domains without protein-protein clashes. The electrophoretic mobility shift assay (EMSA) shows that the ETS protein GABPα and the B-ZIP protein CREB preferentially bind to the ETS⇔CRE motif only when the two TFBS overlap precisely. In contrast, the ETS domain of ETV5 and CREB interfere with each other for binding the ETS⇔CRE. The 11-mer (CGGAAGTGACG), the conserved part of the ETS⇔CRE motif, occurs 226 times in the human genome and 83% are in known regulatory regions. In vivo GABPα and CREB ChIP-seq peaks identified the ETS⇔CRE as the most enriched motif occurring in promoters of genes involved in mRNA processing, cellular catabolic processes, and stress response, suggesting that a specific class of genes is regulated by this composite motif. PMID:23050235

  8. Relative judgment theory and the mediation of facial recognition: Implications for theories of eyewitness identification.

    Science.gov (United States)

    McAdoo, Ryan M; Gronlund, Scott D

    2016-01-01

    Many in the eyewitness identification community believe that sequential lineups are superior to simultaneous lineups because simultaneous lineups encourage inappropriate choosing due to promoting comparisons among choices (a relative judgment strategy), but sequential lineups reduce this propensity by inducing comparisons of lineup members directly to memory rather than to each other (an absolute judgment strategy). Different versions of the relative judgment theory have implicated both discrete-state and continuous mediation of eyewitness decisions. The theory has never been formally specified, but (Yonelinas, J Exp Psychol Learn Mem Cogn 20:1341-1354, 1994) dual-process models provide one possible specification, thereby allowing us to evaluate how eyewitness decisions are mediated. We utilized a ranking task (Kellen and Klauer, J Exp Psychol Learn Mem Cogn 40:1795-1804, 2014) and found evidence for continuous mediation when facial stimuli match from study to test (Experiment 1) and when they mismatch (Experiment 2). This evidence, which is contrary to a version of relative judgment theory that has gained a lot of traction in the legal community, compels reassessment of the role that guessing plays in eyewitness identification. Future research should continue to test formal explanations in order to advance theory, expedite the development of new procedures that can enhance the reliability of eyewitness evidence, and to facilitate the exploration of task factors and emergent strategies that might influence when recognition is continuously or discretely mediated.

  9. oPOSSUM: integrated tools for analysis of regulatory motif over-representation

    Science.gov (United States)

    Ho Sui, Shannan J.; Fulton, Debra L.; Arenillas, David J.; Kwon, Andrew T.; Wasserman, Wyeth W.

    2007-01-01

    The identification of over-represented transcription factor binding sites from sets of co-expressed genes provides insights into the mechanisms of regulation for diverse biological contexts. oPOSSUM, an internet-based system for such studies of regulation, has been improved and expanded in this new release. New features include a worm-specific version for investigating binding sites conserved between Caenorhabditis elegans and C. briggsae, as well as a yeast-specific version for the analysis of co-expressed sets of Saccharomyces cerevisiae genes. The human and mouse applications feature improvements in ortholog mapping, sequence alignments and the delineation of multiple alternative promoters. oPOSSUM2, introduced for the analysis of over-represented combinations of motifs in human and mouse genes, has been integrated with the original oPOSSUM system. Analysis using user-defined background gene sets is now supported. The transcription factor binding site models have been updated to include new profiles from the JASPAR database. oPOSSUM is available at http://www.cisreg.ca/oPOSSUM/ PMID:17576675

  10. ROMANIAN TRADITIONAL MOTIF ELEMENT OF MODERNITY IN CLOTHING

    Directory of Open Access Journals (Sweden)

    ŞUTEU Marius Darius

    2017-05-01

    Full Text Available In this paper are presented the phases for improving from an aesthetic point of view a clothing item, the T-shirt for women using software design patterns, computerised graphics and textile different modern technologies including: industrial embroidery, digital printing, sublimation. In the first phase a documentation was prepared in the University of Oradea and traditional motif was selected from a collection comprising a number of Romanian traditional motifs from different parts of the country and were reintepreted and stylized whilst preserving the symbolism and color range specified to the area. For the styling phase was used CorelDraw vector graphics program that allows changing the shape, size and color of the drawings without affecting the identity of the pattern. The embroidery was done using BERNINA Embroidery Software Designer Plus Software. This software allows you to export the model to any domestic or industrial embroidery machine regardless of brand. Finally we observed the resistance of the printed and embroided model to various: elasticity, resistance to abrasion and a sensory analysis on the preservation of color. After testing we noticed the imprint resistance applied to the fabric, resulting in a quality that makes possible to keep the Romanian traditional motif from generation to generation.

  11. A Novel Protein Interaction between Nucleotide Binding Domain of Hsp70 and p53 Motif

    Directory of Open Access Journals (Sweden)

    Asita Elengoe

    2015-01-01

    Full Text Available Currently, protein interaction of Homo sapiens nucleotide binding domain (NBD of heat shock 70 kDa protein (PDB: 1HJO with p53 motif remains to be elucidated. The NBD-p53 motif complex enhances the p53 stabilization, thereby increasing the tumor suppression activity in cancer treatment. Therefore, we identified the interaction between NBD and p53 using STRING version 9.1 program. Then, we modeled the three-dimensional structure of p53 motif through homology modeling and determined the binding affinity and stability of NBD-p53 motif complex structure via molecular docking and dynamics (MD simulation. Human DNA binding domain of p53 motif (SCMGGMNR retrieved from UniProt (UniProtKB: P04637 was docked with the NBD protein, using the Autodock version 4.2 program. The binding energy and intermolecular energy for the NBD-p53 motif complex were −0.44 Kcal/mol and −9.90 Kcal/mol, respectively. Moreover, RMSD, RMSF, hydrogen bonds, salt bridge, and secondary structure analyses revealed that the NBD protein had a strong bond with p53 motif and the protein-ligand complex was stable. Thus, the current data would be highly encouraging for designing Hsp70 structure based drug in cancer therapy.

  12. Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family

    Science.gov (United States)

    Soufari, Heddy

    2017-01-01

    Precise regulation of mRNA processing, translation, localization, and stability relies on specific interactions with RNA-binding proteins whose biological function and target preference are dictated by their preferred RNA motifs. The RBPMS family of RNA-binding proteins is defined by a conserved RNA recognition motif (RRM) domain found in metazoan RBPMS/Hermes and RBPMS2, Drosophila couch potato, and MEC-8 from Caenorhabditis elegans. In order to determine the parameters of RNA sequence recognition by the RBPMS family, we have first used the N-terminal domain from MEC-8 in binding assays and have demonstrated a preference for two GCAC motifs optimally separated by >6 nucleotides (nt). We have also determined the crystal structure of the dimeric N-terminal RRM domain from MEC-8 in the unbound form, and in complex with an oligonucleotide harboring two copies of the optimal GCAC motif. The atomic details reveal the molecular network that provides specificity to all four bases in the motif, including multiple hydrogen bonds to the initial guanine. Further studies with human RBPMS, as well as Drosophila couch potato, confirm a general preference for this double GCAC motif by other members of the protein family and the presence of this motif in known targets. PMID:28003515

  13. Error analysis of stochastic gradient descent ranking.

    Science.gov (United States)

    Chen, Hong; Tang, Yi; Li, Luoqing; Yuan, Yuan; Li, Xuelong; Tang, Yuanyan

    2013-06-01

    Ranking is always an important task in machine learning and information retrieval, e.g., collaborative filtering, recommender systems, drug discovery, etc. A kernel-based stochastic gradient descent algorithm with the least squares loss is proposed for ranking in this paper. The implementation of this algorithm is simple, and an expression of the solution is derived via a sampling operator and an integral operator. An explicit convergence rate for leaning a ranking function is given in terms of the suitable choices of the step size and the regularization parameter. The analysis technique used here is capacity independent and is novel in error analysis of ranking learning. Experimental results on real-world data have shown the effectiveness of the proposed algorithm in ranking tasks, which verifies the theoretical analysis in ranking error.

  14. Contests with rank-order spillovers

    NARCIS (Netherlands)

    M.R. Baye (Michael); D. Kovenock (Dan); C.G. de Vries (Casper)

    2012-01-01

    textabstractThis paper presents a unified framework for characterizing symmetric equilibrium in simultaneous move, two-player, rank-order contests with complete information, in which each player's strategy generates direct or indirect affine "spillover" effects that depend on the rank-order of her

  15. Parallel motif extraction from very long sequences

    KAUST Repository

    Sahli, Majed; Mansour, Essam; Kalnis, Panos

    2013-01-01

    Motifs are frequent patterns used to identify biological functionality in genomic sequences, periodicity in time series, or user trends in web logs. In contrast to a lot of existing work that focuses on collections of many short sequences, modern

  16. A set of tetra-nucleotide core motif SSR markers for efficient identification of potato (Solanum tuberosum) cultivars.

    Science.gov (United States)

    Kishine, Masahiro; Tsutsumi, Katsuji; Kitta, Kazumi

    2017-12-01

    Simple sequence repeat (SSR) is a popular tool for individual fingerprinting. The long-core motif (e.g. tetra-, penta-, and hexa-nucleotide) simple sequence repeats (SSRs) are preferred because they make it easier to separate and distinguish neighbor alleles. In the present study, a new set of 8 tetra-nucleotide SSRs in potato ( Solanum tuberosum ) is reported. By using these 8 markers, 72 out of 76 cultivars obtained from Japan and the United States were clearly discriminated, while two pairs, both of which arose from natural variation, showed identical profiles. The combined probability of identity between two random cultivars for the set of 8 SSR markers was estimated to be 1.10 × 10 -8 , confirming the usefulness of the proposed SSR markers for fingerprinting analyses of potato.

  17. Efficient sequential and parallel algorithms for planted motif search.

    Science.gov (United States)

    Nicolae, Marius; Rajasekaran, Sanguthevar

    2014-01-31

    Motif searching is an important step in the detection of rare events occurring in a set of DNA or protein sequences. One formulation of the problem is known as (l,d)-motif search or Planted Motif Search (PMS). In PMS we are given two integers l and d and n biological sequences. We want to find all sequences of length l that appear in each of the input sequences with at most d mismatches. The PMS problem is NP-complete. PMS algorithms are typically evaluated on certain instances considered challenging. Despite ample research in the area, a considerable performance gap exists because many state of the art algorithms have large runtimes even for moderately challenging instances. This paper presents a fast exact parallel PMS algorithm called PMS8. PMS8 is the first algorithm to solve the challenging (l,d) instances (25,10) and (26,11). PMS8 is also efficient on instances with larger l and d such as (50,21). We include a comparison of PMS8 with several state of the art algorithms on multiple problem instances. This paper also presents necessary and sufficient conditions for 3 l-mers to have a common d-neighbor. The program is freely available at http://engr.uconn.edu/~man09004/PMS8/. We present PMS8, an efficient exact algorithm for Planted Motif Search. PMS8 introduces novel ideas for generating common neighborhoods. We have also implemented a parallel version for this algorithm. PMS8 can solve instances not solved by any previous algorithms.

  18. Motif finding in DNA sequences based on skipping nonconserved positions in background Markov chains.

    Science.gov (United States)

    Zhao, Xiaoyan; Sze, Sing-Hoi

    2011-05-01

    One strategy to identify transcription factor binding sites is through motif finding in upstream DNA sequences of potentially co-regulated genes. Despite extensive efforts, none of the existing algorithms perform very well. We consider a string representation that allows arbitrary ignored positions within the nonconserved portion of single motifs, and use O(2(l)) Markov chains to model the background distributions of motifs of length l while skipping these positions within each Markov chain. By focusing initially on positions that have fixed nucleotides to define core occurrences, we develop an algorithm to identify motifs of moderate lengths. We compare the performance of our algorithm to other motif finding algorithms on a few benchmark data sets, and show that significant improvement in accuracy can be obtained when the sites are sufficiently conserved within a given sample, while comparable performance is obtained when the site conservation rate is low. A software program (PosMotif ) and detailed results are available online at http://faculty.cse.tamu.edu/shsze/posmotif.

  19. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-09-03

    Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  20. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T.; Wani, Mohan R.

    2010-01-01

    Research highlights: → IL-3 inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. → IL-3 inhibits RANKL-induced JNK activation. → IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. → IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. → IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-κB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  1. Rank distributions: A panoramic macroscopic outlook

    Science.gov (United States)

    Eliazar, Iddo I.; Cohen, Morrel H.

    2014-01-01

    This paper presents a panoramic macroscopic outlook of rank distributions. We establish a general framework for the analysis of rank distributions, which classifies them into five macroscopic "socioeconomic" states: monarchy, oligarchy-feudalism, criticality, socialism-capitalism, and communism. Oligarchy-feudalism is shown to be characterized by discrete macroscopic rank distributions, and socialism-capitalism is shown to be characterized by continuous macroscopic size distributions. Criticality is a transition state between oligarchy-feudalism and socialism-capitalism, which can manifest allometric scaling with multifractal spectra. Monarchy and communism are extreme forms of oligarchy-feudalism and socialism-capitalism, respectively, in which the intrinsic randomness vanishes. The general framework is applied to three different models of rank distributions—top-down, bottom-up, and global—and unveils each model's macroscopic universality and versatility. The global model yields a macroscopic classification of the generalized Zipf law, an omnipresent form of rank distributions observed across the sciences. An amalgamation of the three models establishes a universal rank-distribution explanation for the macroscopic emergence of a prevalent class of continuous size distributions, ones governed by unimodal densities with both Pareto and inverse-Pareto power-law tails.

  2. Importance of intrinsic and non-network contribution in PageRank centrality and its effect on PageRank localization

    OpenAIRE

    Deyasi, Krishanu

    2016-01-01

    PageRank centrality is used by Google for ranking web-pages to present search result for a user query. Here, we have shown that PageRank value of a vertex also depends on its intrinsic, non-network contribution. If the intrinsic, non-network contributions of the vertices are proportional to their degrees or zeros, then their PageRank centralities become proportion to their degrees. Some simulations and empirical data are used to support our study. In addition, we have shown that localization ...

  3. Ranking as parameter estimation

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav; Guy, Tatiana Valentine

    2009-01-01

    Roč. 4, č. 2 (2009), s. 142-158 ISSN 1745-7645 R&D Projects: GA MŠk 2C06001; GA AV ČR 1ET100750401; GA MŠk 1M0572 Institutional research plan: CEZ:AV0Z10750506 Keywords : ranking * Bayesian estimation * negotiation * modelling Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2009/AS/karny- ranking as parameter estimation.pdf

  4. Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W.; Thompson, Larry H.; Schild, David

    2006-04-21

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  5. Temporal motifs reveal collaboration patterns in online task-oriented networks

    Science.gov (United States)

    Xuan, Qi; Fang, Huiting; Fu, Chenbo; Filkov, Vladimir

    2015-05-01

    Real networks feature layers of interactions and complexity. In them, different types of nodes can interact with each other via a variety of events. Examples of this complexity are task-oriented social networks (TOSNs), where teams of people share tasks towards creating a quality artifact, such as academic research papers or software development in commercial or open source environments. Accomplishing those tasks involves both work, e.g., writing the papers or code, and communication, to discuss and coordinate. Taking into account the different types of activities and how they alternate over time can result in much more precise understanding of the TOSNs behaviors and outcomes. That calls for modeling techniques that can accommodate both node and link heterogeneity as well as temporal change. In this paper, we report on methodology for finding temporal motifs in TOSNs, limited to a system of two people and an artifact. We apply the methods to publicly available data of TOSNs from 31 Open Source Software projects. We find that these temporal motifs are enriched in the observed data. When applied to software development outcome, temporal motifs reveal a distinct dependency between collaboration and communication in the code writing process. Moreover, we show that models based on temporal motifs can be used to more precisely relate both individual developer centrality and team cohesion to programmer productivity than models based on aggregated TOSNs.

  6. Salt-bridge Swapping in the EXXERFXYY Motif of Proton Coupled Oligopeptide Transporters

    DEFF Research Database (Denmark)

    Aduri, Nanda G; Prabhala, Bala K; Ernst, Heidi A

    2015-01-01

    to as E1XXE2R), located on Helix I, in interactions with the proton. In this study we investigated the intracellular substrate accumulation by motif variants with all possible combinations of glutamate residues changed to glutamine and arginine changed to a tyrosine; the latter being a natural variant......-motif salt bridge, i.e. R-E2 to R-E1, which is consistent with previous structural studies. Molecular dynamics simulations of the motif variants E1XXE2R and E1XXQ2R support this mechanism. The simulations showed that upon changing conformation, arginine pushes Helix V, through interactions with the highly...

  7. Iterative Neighbour-Information Gathering for Ranking Nodes in Complex Networks

    Science.gov (United States)

    Xu, Shuang; Wang, Pei; Lü, Jinhu

    2017-01-01

    Designing node influence ranking algorithms can provide insights into network dynamics, functions and structures. Increasingly evidences reveal that node’s spreading ability largely depends on its neighbours. We introduce an iterative neighbourinformation gathering (Ing) process with three parameters, including a transformation matrix, a priori information and an iteration time. The Ing process iteratively combines priori information from neighbours via the transformation matrix, and iteratively assigns an Ing score to each node to evaluate its influence. The algorithm appropriates for any types of networks, and includes some traditional centralities as special cases, such as degree, semi-local, LeaderRank. The Ing process converges in strongly connected networks with speed relying on the first two largest eigenvalues of the transformation matrix. Interestingly, the eigenvector centrality corresponds to a limit case of the algorithm. By comparing with eight renowned centralities, simulations of susceptible-infected-removed (SIR) model on real-world networks reveal that the Ing can offer more exact rankings, even without a priori information. We also observe that an optimal iteration time is always in existence to realize best characterizing of node influence. The proposed algorithms bridge the gaps among some existing measures, and may have potential applications in infectious disease control, designing of optimal information spreading strategies.

  8. A Repeating Sulfated Galactan Motif Resuscitates Dormant Micrococcus luteus Bacteria.

    Science.gov (United States)

    Böttcher, Thomas; Szamosvári, Dávid; Clardy, Jon

    2018-07-01

    Only a small fraction of bacteria can autonomously initiate growth on agar plates. Nongrowing bacteria typically enter a metabolically inactive dormant state and require specific chemical trigger factors or signals to exit this state and to resume growth. Micrococcus luteus has become a model organism for this important yet poorly understood phenomenon. Only a few resuscitation signals have been described to date, and all of them are produced endogenously by bacterial species. We report the discovery of a novel type of resuscitation signal that allows M. luteus to grow on agar but not agarose plates. Fractionation of the agar polysaccharide complex and sulfation of agarose allowed us to identify the signal as highly sulfated saccharides found in agar or carrageenans. Purification of hydrolyzed κ-carrageenan ultimately led to the identification of the signal as a small fragment of a large linear polysaccharide, i.e., an oligosaccharide of five or more sugars with a repeating disaccharide motif containing d-galactose-4-sulfate (G4S) 1,4-linked to 3,6-anhydro-α-d-galactose (DA), G4S-(DA-G4S) n ≥2 IMPORTANCE Most environmental bacteria cannot initiate growth on agar plates, but they can flourish on the same plates once growth is initiated. While there are a number of names for and manifestations of this phenomenon, the underlying cause appears to be the requirement for a molecular signal indicating safe growing conditions. Micrococcus luteus has become a model organism for studying this growth initiation process, often called resuscitation, because of its apparent connection with the persistent or dormant form of Mycobacterium tuberculosis , an important human pathogen. In this report, we identify a highly sulfated saccharide from agar or carrageenans that robustly resuscitates dormant M. luteus on agarose plates. We identified and characterized the signal as a small repeating disaccharide motif. Our results indicate that signals inherent in or absent from the

  9. Systematic discovery of regulatory motifs in Fusarium graminearum by comparing four Fusarium genomes

    Directory of Open Access Journals (Sweden)

    Kistler Corby

    2010-03-01

    Full Text Available Abstract Background Fusarium graminearum (Fg, a major fungal pathogen of cultivated cereals, is responsible for billions of dollars in agriculture losses. There is a growing interest in understanding the transcriptional regulation of this organism, especially the regulation of genes underlying its pathogenicity. The generation of whole genome sequence assemblies for Fg and three closely related Fusarium species provides a unique opportunity for such a study. Results Applying comparative genomics approaches, we developed a computational pipeline to systematically discover evolutionarily conserved regulatory motifs in the promoter, downstream and the intronic regions of Fg genes, based on the multiple alignments of sequenced Fusarium genomes. Using this method, we discovered 73 candidate regulatory motifs in the promoter regions. Nearly 30% of these motifs are highly enriched in promoter regions of Fg genes that are associated with a specific functional category. Through comparison to Saccharomyces cerevisiae (Sc and Schizosaccharomyces pombe (Sp, we observed conservation of transcription factors (TFs, their binding sites and the target genes regulated by these TFs related to pathways known to respond to stress conditions or phosphate metabolism. In addition, this study revealed 69 and 39 conserved motifs in the downstream regions and the intronic regions, respectively, of Fg genes. The top intronic motif is the splice donor site. For the downstream regions, we noticed an intriguing absence of the mammalian and Sc poly-adenylation signals among the list of conserved motifs. Conclusion This study provides the first comprehensive list of candidate regulatory motifs in Fg, and underscores the power of comparative genomics in revealing functional elements among related genomes. The conservation of regulatory pathways among the Fusarium genomes and the two yeast species reveals their functional significance, and provides new insights in their

  10. Locating Leaks with TrustRank Algorithm Support

    Directory of Open Access Journals (Sweden)

    Luísa Ribeiro

    2015-03-01

    Full Text Available This paper presents a methodology to quantify and to locate leaks. The original contribution is the use of a tool based on the TrustRank algorithm for the selection of nodes for pressure monitoring. The results from these methodologies presented here are: (I A sensitivity analysis of the number of pressure transducers on the quality of the final solution; (II A reduction of the number of pipes to be inspected; and (III A focus on the problematic pipes which allows a better office planning of the inspection works to perform atthe field. To obtain these results, a methodology for the identification of probable leaky pipes and an estimate of their leakage flows is also presented. The potential of the methodology is illustrated with several case studies, considering different levels of water losses and different sets of pressure monitoring nodes. The results are discussed and the solutions obtained show the benefits of the developed methodologies.

  11. Through the Portal: Viking Motifs Incorporated in the Romanesque Style in Telemark, Norway

    Directory of Open Access Journals (Sweden)

    Kristine Ødeby

    2013-09-01

    Full Text Available This paper presents the results of an analysis of motifs identified on six carved wooden Romanesque portal panels from the Norwegian county of Telemark. The findings suggest that animal motifs in the Late Viking style survived long into the Late Medieval period and were reused on these medieval portals. Stylistically, late expressions of Viking animal art do not differ a great deal from those of the subsequent Romanesque style. However, their symbolical differences are considered to be significant. The motifs themselves, and the issue of whether the Romanesque style adopted motifs from pre-Christian art, have attracted less attention. The motif portraying Sigurd slaying the dragon is considered in depth. It will be suggested that Sigurd, serving as a mediator between the old and the new beliefs when he appeared in late Viking contexts, was given a new role when portrayed in Christian art. Metaphor and liminality are a central part of this paper, and the theories of Alfred Gell and Margrete Andås suggest that the portal itself affects those who pass through it, and that the iconography is meaningful from a liminal perspective.

  12. Dragon polya spotter: Predictor of poly(A) motifs within human genomic DNA sequences

    KAUST Repository

    Kalkatawi, Manal M.

    2011-11-15

    Motivation: Recognition of poly(A) signals in mRNA is relatively straightforward due to the presence of easily recognizable polyadenylic acid tail. However, the task of identifying poly(A) motifs in the primary genomic DNA sequence that correspond to poly(A) signals in mRNA is a far more challenging problem. Recognition of poly(A) signals is important for better gene annotation and understanding of the gene regulation mechanisms. In this work, we present one such poly(A) motif prediction method based on properties of human genomic DNA sequence surrounding a poly(A) motif. These properties include thermodynamic, physico-chemical and statistical characteristics. For predictions, we developed Artificial Neural Network and Random Forest models. These models are trained to recognize 12 most common poly(A) motifs in human DNA. Our predictors are available as a free web-based tool accessible at http://cbrc.kaust.edu.sa/dps. Compared with other reported predictors, our models achieve higher sensitivity and specificity and furthermore provide a consistent level of accuracy for 12 poly(A) motif variants. The Author(s) 2011. Published by Oxford University Press. All rights reserved.

  13. qPMS7: a fast algorithm for finding (ℓ, d-motifs in DNA and protein sequences.

    Directory of Open Access Journals (Sweden)

    Hieu Dinh

    Full Text Available Detection of rare events happening in a set of DNA/protein sequences could lead to new biological discoveries. One kind of such rare events is the presence of patterns called motifs in DNA/protein sequences. Finding motifs is a challenging problem since the general version of motif search has been proven to be intractable. Motifs discovery is an important problem in biology. For example, it is useful in the detection of transcription factor binding sites and transcriptional regulatory elements that are very crucial in understanding gene function, human disease, drug design, etc. Many versions of the motif search problem have been proposed in the literature. One such is the (ℓ, d-motif search (or Planted Motif Search (PMS. A generalized version of the PMS problem, namely, Quorum Planted Motif Search (qPMS, is shown to accurately model motifs in real data. However, solving the qPMS problem is an extremely difficult task because a special case of it, the PMS Problem, is already NP-hard, which means that any algorithm solving it can be expected to take exponential time in the worse case scenario. In this paper, we propose a novel algorithm named qPMS7 that tackles the qPMS problem on real data as well as challenging instances. Experimental results show that our Algorithm qPMS7 is on an average 5 times faster than the state-of-art algorithm. The executable program of Algorithm qPMS7 is freely available on the web at http://pms.engr.uconn.edu/downloads/qPMS7.zip. Our online motif discovery tools that use Algorithm qPMS7 are freely available at http://pms.engr.uconn.edu or http://motifsearch.com.

  14. Diversifying customer review rankings.

    Science.gov (United States)

    Krestel, Ralf; Dokoohaki, Nima

    2015-06-01

    E-commerce Web sites owe much of their popularity to consumer reviews accompanying product descriptions. On-line customers spend hours and hours going through heaps of textual reviews to decide which products to buy. At the same time, each popular product has thousands of user-generated reviews, making it impossible for a buyer to read everything. Current approaches to display reviews to users or recommend an individual review for a product are based on the recency or helpfulness of each review. In this paper, we present a framework to rank product reviews by optimizing the coverage of the ranking with respect to sentiment or aspects, or by summarizing all reviews with the top-K reviews in the ranking. To accomplish this, we make use of the assigned star rating for a product as an indicator for a review's sentiment polarity and compare bag-of-words (language model) with topic models (latent Dirichlet allocation) as a mean to represent aspects. Our evaluation on manually annotated review data from a commercial review Web site demonstrates the effectiveness of our approach, outperforming plain recency ranking by 30% and obtaining best results by combining language and topic model representations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs

    KAUST Repository

    Alam, Tanvir

    2014-05-29

    LD motifs (leucine-aspartic acidmotifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs. © 2014 Biochemical Society.

  16. How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs

    KAUST Repository

    Alam, Tanvir; Alazmi, Meshari; Gao, Xin; Arold, Stefan T.

    2014-01-01

    LD motifs (leucine-aspartic acidmotifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs. © 2014 Biochemical Society.

  17. Ranking of healthcare programmes based on health outcome, health costs and safe delivery of care in hospital pharmacy practice.

    Science.gov (United States)

    Brisseau, Lionel; Bussières, Jean-François; Bois, Denis; Vallée, Marc; Racine, Marie-Claude; Bonnici, André

    2013-02-01

    To establish a consensual and coherent ranking of healthcare programmes that involve the presence of ward-based and clinic-based clinical pharmacists, based on health outcome, health costs and safe delivery of care. This descriptive study was derived from a structured dialogue (Delphi technique) among directors of pharmacy department. We established a quantitative profile of healthcare programmes at five sites that involved the provision of ward-based and clinic-based pharmaceutical care. A summary table of evidence established a unique quality rating per inpatient (clinic-based) or outpatient (ward-based) healthcare programme. Each director rated the perceived impact of pharmaceutical care per inpatient or outpatient healthcare programme on three fields: health outcome, health costs and safe delivery of care. They agreed by consensus on the final ranking of healthcare programmes. A ranking was assigned for each of the 18 healthcare programmes for outpatient care and the 17 healthcare programmes for inpatient care involving the presence of pharmacists, based on health outcome, health costs and safe delivery of care. There was a good correlation between ranking based on data from a 2007-2008 Canadian report on hospital pharmacy practice and the ranking proposed by directors of pharmacy department. Given the often limited human and financial resources, managers should consider the best evidence available on a profession's impact to plan healthcare services within an organization. Data are few on ranking healthcare programmes in order to prioritize which healthcare programme would mostly benefit from the delivery of pharmaceutical care by ward-based and clinic-based pharmacists. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.

  18. Literature evidence in open targets - a target validation platform.

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

    We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

  19. I-Ad-binding peptides derived from unrelated protein antigens share a common structural motif

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Colon, S

    1988-01-01

    on the I-Ad binding of the immunogenic peptide OVA 323-339. The results obtained demonstrated the very permissive nature of Ag-Ia interaction. We also showed that unrelated peptides that are good I-Ad binders share a common structural motif and speculated that recognition of such motifs could represent...... that I-Ad molecules recognize a large library of Ag by virtue of common structural motifs present in peptides derived from phylogenetically unrelated proteins....

  20. Journal Rankings by Health Management Faculty Members: Are There Differences by Rank, Leadership Status, or Area of Expertise?

    Science.gov (United States)

    Menachemi, Nir; Hogan, Tory H; DelliFraine, Jami L

    2015-01-01

    Health administration (HA) faculty members publish in a variety of journals, including journals focused on management, economics, policy, and information technology. HA faculty members are evaluated on the basis of the quality and quantity of their journal publications. However, it is unclear how perceptions of these journals vary by subdiscipline, department leadership role, or faculty rank. It is also not clear how perceptions of journals may have changed over the past decade since the last evaluation of journal rankings in the field was published. The purpose of the current study is to examine how respondents rank journals in the field of HA, as well as the variation in perception by academic rank, department leadership status, and area of expertise. Data were drawn from a survey of HA faculty members at U.S. universities, which was completed in 2012. Different journal ranking patterns were noted for faculty members of different subdisciplines. The health management-oriented journals (Health Care Management Review and Journal of Healthcare Management) were ranked higher than in previous research, suggesting that journal ranking perceptions may have changed over the intervening decade. Few differences in perceptions were noted by academic rank, but we found that department chairs were more likely than others to select Health Affairs in their top three most prestigious journals (β = 0.768; p journal prestige varied between a department chair and untenured faculty in different disciplines, and this perceived difference could have implications for promotion and tenure decisions.

  1. How journal rankings can suppress interdisciplinary research: a comparison between innovation studies and business & management

    NARCIS (Netherlands)

    Rafols, I.; Leydesdorff, L.; O'Hare, A.; Nightingale, P.; Stirling, A.

    2012-01-01

    This study provides quantitative evidence on how the use of journal rankings can disadvantage interdisciplinary research in research evaluations. Using publication and citation data, it compares the degree of interdisciplinarity and the research performance of a number of Innovation Studies units

  2. Algebraic and computational aspects of real tensor ranks

    CERN Document Server

    Sakata, Toshio; Miyazaki, Mitsuhiro

    2016-01-01

    This book provides comprehensive summaries of theoretical (algebraic) and computational aspects of tensor ranks, maximal ranks, and typical ranks, over the real number field. Although tensor ranks have been often argued in the complex number field, it should be emphasized that this book treats real tensor ranks, which have direct applications in statistics. The book provides several interesting ideas, including determinant polynomials, determinantal ideals, absolutely nonsingular tensors, absolutely full column rank tensors, and their connection to bilinear maps and Hurwitz-Radon numbers. In addition to reviews of methods to determine real tensor ranks in details, global theories such as the Jacobian method are also reviewed in details. The book includes as well an accessible and comprehensive introduction of mathematical backgrounds, with basics of positive polynomials and calculations by using the Groebner basis. Furthermore, this book provides insights into numerical methods of finding tensor ranks through...

  3. Substantial injuries influence ranking position in young elite athletes of athletics, cross-country skiing and orienteering.

    Science.gov (United States)

    von Rosen, P; Heijne, A

    2018-04-01

    The relationship between injury and performance in young athletes is scarcely studied. The aim of this study was therefore to explore the association between injury prevalence and ranking position among adolescent elite athletes. One hundred and sixty-two male and female adolescent elite athletes (age range 15-19), competing in athletics (n = 59), cross-country skiing (n = 66), and orienteering (n = 37), were monitored weekly over 22-47 weeks using a web-based injury questionnaire. Ranking lists were collected. A significant (P = .003) difference was found in the seasonal substantial injury prevalence across the ranked athletes over the season, where the top-ranked (median 3.6%, 25-75th percentiles 0%-14.3%) and middle-ranked athletes (median 2.3%, 25-75th percentiles 0%-10.0%) had a lower substantial injury prevalence compared to the low-ranked athletes (median 11.3%, 25-75th percentiles 2.5%-27.1%), during both preseason (P = .002) and competitive season (P = .031). Athletes who improved their ranking position (51%, n = 51) reported a lower substantial injury prevalence (median 0%, 25-75th percentiles 0%-10.0%) compared to those who decreased (49%, n = 49) their ranking position (md 6.7%, 25-75th percentiles 0%-22.5%). In the top-ranked group, no athlete reported substantial injury more than 40% of all data collection time points compared to 9.6% (n = 5) in the middle-ranked, and 17.3% (n = 9) in the low-ranked group. Our results provide supporting evidence that substantial injuries, such as acute and overuse injuries leading to moderate or severe reductions in training or sports performance, influence ranking position in adolescent elite athletes. The findings are crucial to stakeholders involved in adolescent elite sports and support the value of designing effective preventive interventions for substantial injuries. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

    Directory of Open Access Journals (Sweden)

    Arnoldo J Müller-Molina

    Full Text Available To know the map between transcription factors (TFs and their binding sites is essential to reverse engineer the regulation process. Only about 10%-20% of the transcription factor binding motifs (TFBMs have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory "DNA words." From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%-far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of "DNA words," newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters.

  5. Memfasilitasi Penalaran Geometri Transformasi Siswa Melalui Eksplorasi Motif Melayu dengan Bantuan Grid

    Directory of Open Access Journals (Sweden)

    Febrian Febrian

    2017-10-01

    Full Text Available Geometri transformasi merupakan pengetahuan yang krusial dalam geometri yang dapat membangun banyak kemampuan lainnya seperti penalaran matematis. Oleh karena itu, geometri transformasi disarankan untuk diberikan pada pebelajar mulai dari usia dini. Penelitian terdahulu menunjukkan bahwa anak-anak memiliki sense untuk melihat karakteristik kedinamisan pada benda, oleh karena itu memfasilitasi pembelajaran yang dapat memanfaatkan sense ini menjadi sangat penting untuk membangun pemahaman geometri transformasi. Penelitian design research ini bertujuan untuk memfasilitasi siswa sekolah dasar untuk dapat mengembangkan pengetahuan awal mereka mengenai komposisi transformasi. Subjek penelitian adalah siswa kelas IV Sekolah Dasar Negeri 001 Toapaya, Kabupaten Bintan, Kepulauan Riau. Pendekatan pembelajaran yang digunakan adalah PMRI dengan konteks motif melayu itik pulang petang dengan bantuan grid. Hasil menunjukkan bahwa setting pembelajaran dapat memfasilitasi penalaran geometri transformasi melalui kegiatan eksplorasi motif dengan bantuan grid. Kata Kunci: komposisi transformasi, penalaran, motif melayu, grid, PMRI Transformation geometry is a crucial knowledge in geometry that can emerge many skills especially mathematical reasoning. Therefore, transformation geometry is suggested to be taught to children especially the young learners. Existing research implies that children have particular sense to see dynamic characteristic of an object or others. On the behalf of this statement, facilitating students in learning process that makes use of this students sense becomes important to undertake to help develop students reasoning of transformation geometry. The subtopic being highlighted is the composition of transformation. This design research aims to facilitate this situation. The subject of the research is fourth graders of the State Elementary School of 001 at Toapaya, Kabupaten Bintan, Kepulauan Riau. The learning approach used was PMRI by using

  6. Two sequence motifs from HIF-1α bind to the DNA-binding site of p53

    OpenAIRE

    Hansson, Lars O.; Friedler, Assaf; Freund, Stefan; Rüdiger, Stefan; Fersht, Alan R.

    2002-01-01

    There is evidence that hypoxia-inducible factor-1α (HIF-1α) interacts with the tumor suppressor p53. To characterize the putative interaction, we mapped the binding of the core domain of p53 (p53c) to an array of immobilized HIF-1α-derived peptides and found two peptide-sequence motifs that bound to p53c with micromolar affinity in solution. One sequence was adjacent to and the other coincided with the two proline residues of the oxygen-dependent degradation domain (P402 and P564) that act as...

  7. Augmenting the Deliberative Method for Ranking Risks.

    Science.gov (United States)

    Susel, Irving; Lasley, Trace; Montezemolo, Mark; Piper, Joel

    2016-01-01

    The Department of Homeland Security (DHS) characterized and prioritized the physical cross-border threats and hazards to the nation stemming from terrorism, market-driven illicit flows of people and goods (illegal immigration, narcotics, funds, counterfeits, and weaponry), and other nonmarket concerns (movement of diseases, pests, and invasive species). These threats and hazards pose a wide diversity of consequences with very different combinations of magnitudes and likelihoods, making it very challenging to prioritize them. This article presents the approach that was used at DHS to arrive at a consensus regarding the threats and hazards that stand out from the rest based on the overall risk they pose. Due to time constraints for the decision analysis, it was not feasible to apply multiattribute methodologies like multiattribute utility theory or the analytic hierarchy process. Using a holistic approach was considered, such as the deliberative method for ranking risks first published in this journal. However, an ordinal ranking alone does not indicate relative or absolute magnitude differences among the risks. Therefore, the use of the deliberative method for ranking risks is not sufficient for deciding whether there is a material difference between the top-ranked and bottom-ranked risks, let alone deciding what the stand-out risks are. To address this limitation of ordinal rankings, the deliberative method for ranking risks was augmented by adding an additional step to transform the ordinal ranking into a ratio scale ranking. This additional step enabled the selection of stand-out risks to help prioritize further analysis. © 2015 Society for Risk Analysis.

  8. CmMDb: a versatile database for Cucumis melo microsatellite markers and other horticulture crop research.

    Science.gov (United States)

    Bhawna; Chaduvula, Pavan K; Bonthala, Venkata S; Manjusha, Verma; Siddiq, Ebrahimali A; Polumetla, Ananda K; Prasad, Gajula M N V

    2015-01-01

    Cucumis melo L. that belongs to Cucurbitaceae family ranks among one of the highest valued horticulture crops being cultivated across the globe. Besides its economical and medicinal importance, Cucumis melo L. is a valuable resource and model system for the evolutionary studies of cucurbit family. However, very limited numbers of molecular markers were reported for Cucumis melo L. so far that limits the pace of functional genomic research in melon and other similar horticulture crops. We developed the first whole genome based microsatellite DNA marker database of Cucumis melo L. and comprehensive web resource that aids in variety identification and physical mapping of Cucurbitaceae family. The Cucumis melo L. microsatellite database (CmMDb: http://65.181.125.102/cmmdb2/index.html) encompasses 39,072 SSR markers along with its motif repeat, motif length, motif sequence, marker ID, motif type and chromosomal locations. The database is featured with novel automated primer designing facility to meet the needs of wet lab researchers. CmMDb is a freely available web resource that facilitates the researchers to select the most appropriate markers for marker-assisted selection in melons and to improve breeding strategies.

  9. Support vector methods for survival analysis: a comparison between ranking and regression approaches.

    Science.gov (United States)

    Van Belle, Vanya; Pelckmans, Kristiaan; Van Huffel, Sabine; Suykens, Johan A K

    2011-10-01

    To compare and evaluate ranking, regression and combined machine learning approaches for the analysis of survival data. The literature describes two approaches based on support vector machines to deal with censored observations. In the first approach the key idea is to rephrase the task as a ranking problem via the concordance index, a problem which can be solved efficiently in a context of structural risk minimization and convex optimization techniques. In a second approach, one uses a regression approach, dealing with censoring by means of inequality constraints. The goal of this paper is then twofold: (i) introducing a new model combining the ranking and regression strategy, which retains the link with existing survival models such as the proportional hazards model via transformation models; and (ii) comparison of the three techniques on 6 clinical and 3 high-dimensional datasets and discussing the relevance of these techniques over classical approaches fur survival data. We compare svm-based survival models based on ranking constraints, based on regression constraints and models based on both ranking and regression constraints. The performance of the models is compared by means of three different measures: (i) the concordance index, measuring the model's discriminating ability; (ii) the logrank test statistic, indicating whether patients with a prognostic index lower than the median prognostic index have a significant different survival than patients with a prognostic index higher than the median; and (iii) the hazard ratio after normalization to restrict the prognostic index between 0 and 1. Our results indicate a significantly better performance for models including regression constraints above models only based on ranking constraints. This work gives empirical evidence that svm-based models using regression constraints perform significantly better than svm-based models based on ranking constraints. Our experiments show a comparable performance for methods

  10. The city as a motif in Slovene youth literature

    Directory of Open Access Journals (Sweden)

    Milena Mileva Blažić

    2003-01-01

    Full Text Available The article presents the city as motif of Slovenian youth literature in four different periods, beginning in the first period of original Slovenian youth literature in the second half of the 19th century, second period in the first half of the 20th century, third period in the second half of the 20th century and after 1950, when significant books were produced in the field of short modern stories, emphasising on picture books and realistic narrative prose, and the fourth period after 1990. A discernable shift can be observed in the thirties of the 20th century, during the times of socialist realism. The most significant change occurred after 1960, when massive migration from rural to urban environments caused by industrialisation began. The motif of urban environment especially marked modern realistic narrative, coined problematic narrative after 1990, with its focus on issues of growing up in such environments. The city as motif or theme doesn’t appear only in realistic narrative, but since the early 20th century also in fantastic narrative, thus it dichotomically presents the image of real world in Slovenian youth realistic narrative.

  11. Sequence motifs in MADS transcription factors responsible for specificity and diversification of protein-protein interaction.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

    Full Text Available Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important family of transcription regulators has expanded enormously in plant species and contains over 100 members in the model plant species Arabidopsis thaliana. Here, we provide insight into the mechanisms that determine protein-protein interaction specificity for the Arabidopsis MADS domain transcription factor family, using an integrated computational and experimental approach. Plant MADS proteins have highly similar amino acid sequences, but their dimerization patterns vary substantially. Our computational analysis uncovered small sequence regions that explain observed differences in dimerization patterns with reasonable accuracy. Furthermore, we show the usefulness of the method for prediction of MADS domain transcription factor interaction networks in other plant species. Introduction of mutations in the predicted interaction motifs demonstrated that single amino acid mutations can have a large effect and lead to loss or gain of specific interactions. In addition, various performed bioinformatics analyses shed light on the way evolution has shaped MADS domain transcription factor interaction specificity. Identified protein-protein interaction motifs appeared to be strongly conserved among orthologs, indicating their evolutionary importance. We also provide evidence that mutations in these motifs can be a source for sub- or neo-functionalization. The analyses presented here take us a step forward in understanding protein-protein interactions and the interplay between protein sequences and

  12. Model of Decision Making through Consensus in Ranking Case

    Science.gov (United States)

    Tarigan, Gim; Darnius, Open

    2018-01-01

    The basic problem to determine ranking consensus is a problem to combine some rankings those are decided by two or more Decision Maker (DM) into ranking consensus. DM is frequently asked to present their preferences over a group of objects in terms of ranks, for example to determine a new project, new product, a candidate in a election, and so on. The problem in ranking can be classified into two major categories; namely, cardinal and ordinal rankings. The objective of the study is to obtin the ranking consensus by appying some algorithms and methods. The algorithms and methods used in this study were partial algorithm, optimal ranking consensus, BAK (Borde-Kendal)Model. A method proposed as an alternative in ranking conssensus is a Weighted Distance Forward-Backward (WDFB) method, which gave a little difference i ranking consensus result compare to the result oethe example solved by Cook, et.al (2005).

  13. Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses.

    Science.gov (United States)

    Bergmann, Tobias; Lindvall, Mikaela; Moore, Erin; Moore, Eugene; Sidney, John; Miller, Donald; Tallmadge, Rebecca L; Myers, Paisley T; Malaker, Stacy A; Shabanowitz, Jeffrey; Osterrieder, Nikolaus; Peters, Bjoern; Hunt, Donald F; Antczak, Douglas F; Sette, Alessandro

    2017-05-01

    Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Utilizing analyses of endogenously bound and eluted ligands and the screening of positional scanning combinatorial libraries, detailed and quantitative peptide-binding motifs were derived for both alleles. Eqca-16*00101 preferentially binds peptides with aliphatic/hydrophobic residues in position 2 and at the C-terminus, and Eqca-1*00201 has a preference for peptides with arginine in position 2 and hydrophobic/aliphatic residues at the C-terminus. Interestingly, the Eqca-16*00101 motif resembles that of the human HLA A02-supertype, while the Eqca-1*00201 motif resembles that of the HLA B27-supertype and two macaque class I alleles. It is expected that the identified motifs will facilitate the selection of candidate epitopes for the study of immune responses in horses.

  14. High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif

    NARCIS (Netherlands)

    Senchou, V.; Weide, R.L.; Carrasco, A.; Bouyssou, H.; Pont-Lezica, R.; Govers, F.; Canut, H.

    2004-01-01

    The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and

  15. Towards complete sets of farnesylated and geranylgeranylated proteins.

    Directory of Open Access Journals (Sweden)

    Sebastian Maurer-Stroh

    2007-04-01

    Full Text Available Three different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein-protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their mode of action remains unclear since the known substrate sets of the various prenyltransferases are incomplete. The Prenylation Prediction Suite (PrePS has been applied for large-scale predictions of prenylated proteins. To prioritize targets for experimental verification, we rank the predictions by their functional importance estimated by evolutionary conservation of the prenylation motifs within protein families. The ranked lists of predictions are accessible as PRENbase (http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase and can be queried for verification status, type of modifying enzymes (anchor type, and taxonomic distribution. Our results highlight a large group of plant metal-binding chaperones as well as several newly predicted proteins involved in ubiquitin-mediated protein degradation, enriching the known functional repertoire of prenylated proteins. Furthermore, we identify two possibly prenylated proteins in Mimivirus. The section HumanPRENbase provides complete lists of predicted prenylated human proteins-for example, the list of farnesyltransferase targets that cannot become substrates of geranylgeranyltransferase 1 and, therefore, are especially affected by farnesyltransferase inhibitors (FTIs used in cancer and anti-parasite therapy. We report direct experimental evidence verifying the prediction of the human proteins Prickle1, Prickle2, the BRO1 domain-containing FLJ32421 (termed BROFTI, and Rab28 (short isoform as exclusive farnesyltransferase targets. We introduce PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif. Experimental evidence is presented for

  16. DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166

    Directory of Open Access Journals (Sweden)

    Miriam Bothe

    2015-02-01

    Full Text Available The Gram-negative, intracellular bacterium Chlamydia trachomatis causes acute and chronic urogenital tract infection, potentially leading to infertility and ectopic pregnancy. The only partially characterized cytotoxin CT166 of serovar D exhibits a DXD motif, which is important for the enzymatic activity of many bacterial and mammalian type A glycosyltransferases, leading to the hypothesis that CT166 possess glycosyltransferase activity. CT166-expressing HeLa cells exhibit actin reorganization, including cell rounding, which has been attributed to the inhibition of the Rho-GTPases Rac/Cdc42. Exploiting the glycosylation-sensitive Ras(27H5 antibody, we here show that CT166 induces an epitope change in Ras, resulting in inhibited ERK and PI3K signaling and delayed cell cycle progression. Consistent with the hypothesis that these effects strictly depend on the DXD motif, CT166 with the mutated DXD motif causes neither Ras-ERK inhibition nor delayed cell cycle progression. In contrast, CT166 with the mutated DXD motif is still capable of inhibiting cell migration, suggesting that CT166 with the mutated DXD motif cannot be regarded as inactive in any case. Taken together, CT166 affects various fundamental cellular processes, strongly suggesting its importance for the intracellular survival of chlamydia.

  17. The Privilege of Ranking: Google Plays Ball.

    Science.gov (United States)

    Wiggins, Richard

    2003-01-01

    Discussion of ranking systems used in various settings, including college football and academic admissions, focuses on the Google search engine. Explains the PageRank mathematical formula that scores Web pages by connecting the number of links; limitations, including authenticity and accuracy of ranked Web pages; relevancy; adjusting algorithms;…

  18. Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs.

    Science.gov (United States)

    Stinson, Julie; Inoue, Toshiaki; Yates, Paula; Clancy, Anne; Norton, John D; Sharrocks, Andrew D

    2003-08-15

    DNA binding by the ternary complex factor (TCF) subfamily of ETS-domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix-loop-helix (HLH)-containing Id proteins are trans-acting negative regulators of DNA binding by the TCFs. In the TCF, SAP-2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis-acting NID region that also contains an HLH-like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP-1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin-Cdk complexes results in reduction in protein-protein interactions between the Ids and TCFs and relief of their DNA-binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans-acting Id HLH proteins are themselves regulated by phosphorylation.

  19. Alanine substitutions in the GXXXG motif alter C99 cleavage by γ-secretase but not its dimerization.

    Science.gov (United States)

    Higashide, Hidekazu; Ishihara, Seiko; Nobuhara, Mika; Ihara, Yasuo; Funamoto, Satoru

    2017-03-01

    The amyloid β (Aβ) protein is a major component of senile plaques, one of the neuropathological hallmarks of Alzheimer's disease. Amyloidogenic processing of amyloid precursor protein (APP) by β- and γ-secretases leads to production of Aβ. APP contains tandem triple repeats of the GXXXG motif in its extracellular juxtamembrane and transmembrane regions. It is reported that the GXXXG motif is related to protein-protein interactions, but it remains controversial whether the GXXXG motif in APP is involved in substrate dimerization and whether dimerization affects γ-secretase-dependent cleavage. Therefore, the relationship between the GXXXG motifs, substrate dimerization, and γ-secretase-dependent cleavage sites remains unclear. Here, we applied blue native poly acrylamide gel electrophoresis to examine the effect of alanine substitutions within the GXXXG motifs of APP carboxyl terminal fragment (C99) on its dimerization and Aβ production. Surprisingly, alanine substitutions in the motif failed to alter C99 dimerization in detergent soluble state. Cell-based and solubilized γ-secretase assays demonstrated that increasing alanine substitutions in the motif tended to decrease long Aβ species such as Aβ42 and Aβ43 and to increase in short Aβ species concomitantly. Our data suggest that the GXXXG motif is crucial for Aβ production, but not for C99 dimerization. © 2016 International Society for Neurochemistry.

  20. Probabilistic relation between In-Degree and PageRank

    NARCIS (Netherlands)

    Litvak, Nelli; Scheinhardt, Willem R.W.; Volkovich, Y.

    2008-01-01

    This paper presents a novel stochastic model that explains the relation between power laws of In-Degree and PageRank. PageRank is a popularity measure designed by Google to rank Web pages. We model the relation between PageRank and In-Degree through a stochastic equation, which is inspired by the

  1. Identification of Successive ``Unobservable'' Cyber Data Attacks in Power Systems Through Matrix Decomposition

    Science.gov (United States)

    Gao, Pengzhi; Wang, Meng; Chow, Joe H.; Ghiocel, Scott G.; Fardanesh, Bruce; Stefopoulos, George; Razanousky, Michael P.

    2016-11-01

    This paper presents a new framework of identifying a series of cyber data attacks on power system synchrophasor measurements. We focus on detecting "unobservable" cyber data attacks that cannot be detected by any existing method that purely relies on measurements received at one time instant. Leveraging the approximate low-rank property of phasor measurement unit (PMU) data, we formulate the identification problem of successive unobservable cyber attacks as a matrix decomposition problem of a low-rank matrix plus a transformed column-sparse matrix. We propose a convex-optimization-based method and provide its theoretical guarantee in the data identification. Numerical experiments on actual PMU data from the Central New York power system and synthetic data are conducted to verify the effectiveness of the proposed method.

  2. PageRank, HITS and a unified framework for link analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Chris; He, Xiaofeng; Husbands, Parry; Zha, Hongyuan; Simon, Horst

    2001-10-01

    Two popular webpage ranking algorithms are HITS and PageRank. HITS emphasizes mutual reinforcement between authority and hub webpages, while PageRank emphasizes hyperlink weight normalization and web surfing based on random walk models. We systematically generalize/combine these concepts into a unified framework. The ranking framework contains a large algorithm space; HITS and PageRank are two extreme ends in this space. We study several normalized ranking algorithms which are intermediate between HITS and PageRank, and obtain closed-form solutions. We show that, to first order approximation, all ranking algorithms in this framework, including PageRank and HITS, lead to same ranking which is highly correlated with ranking by indegree. These results support the notion that in web resource ranking indegree and outdegree are of fundamental importance. Rankings of webgraphs of different sizes and queries are presented to illustrate our analysis.

  3. Ligand identification using electron-density map correlations

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

    2007-01-01

    An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

  4. Generalized PageRank on Directed Configuration Networks

    NARCIS (Netherlands)

    Chen, Ningyuan; Litvak, Nelli; Olvera-Cravioto, Mariana

    2017-01-01

    Note: formula is not displayed correctly. This paper studies the distribution of a family of rankings, which includes Google’s PageRank, on a directed configuration model. In particular, it is shown that the distribution of the rank of a randomly chosen node in the graph converges in distribution to

  5. Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination.

    Science.gov (United States)

    Wiese, Claudia; Hinz, John M; Tebbs, Robert S; Nham, Peter B; Urbin, Salustra S; Collins, David W; Thompson, Larry H; Schild, David

    2006-01-01

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks (ICLs). Ectopic expression of wild-type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  6. OutRank

    DEFF Research Database (Denmark)

    Müller, Emmanuel; Assent, Ira; Steinhausen, Uwe

    2008-01-01

    Outlier detection is an important data mining task for consistency checks, fraud detection, etc. Binary decision making on whether or not an object is an outlier is not appropriate in many applications and moreover hard to parametrize. Thus, recently, methods for outlier ranking have been proposed...

  7. Ranking Theory and Conditional Reasoning.

    Science.gov (United States)

    Skovgaard-Olsen, Niels

    2016-05-01

    Ranking theory is a formal epistemology that has been developed in over 600 pages in Spohn's recent book The Laws of Belief, which aims to provide a normative account of the dynamics of beliefs that presents an alternative to current probabilistic approaches. It has long been received in the AI community, but it has not yet found application in experimental psychology. The purpose of this paper is to derive clear, quantitative predictions by exploiting a parallel between ranking theory and a statistical model called logistic regression. This approach is illustrated by the development of a model for the conditional inference task using Spohn's (2013) ranking theoretic approach to conditionals. Copyright © 2015 Cognitive Science Society, Inc.

  8. The structure of completely positive matrices according to their CP-rank and CP-plus-rank

    NARCIS (Netherlands)

    Dickinson, Peter James Clair; Bomze, Immanuel M.; Still, Georg J.

    2015-01-01

    We study the topological properties of the cp-rank operator $\\mathrm{cp}(A)$ and the related cp-plus-rank operator $\\mathrm{cp}^+(A)$ (which is introduced in this paper) in the set $\\mathcal{S}^n$ of symmetric $n\\times n$-matrices. For the set of completely positive matrices, $\\mathcal{CP}^n$, we

  9. Identification and characterization of genes responsible for biosynthesis of kojic acid, an industrially important compound from Aspergillus oryzae.

    Science.gov (United States)

    Terabayashi, Yasunobu; Sano, Motoaki; Yamane, Noriko; Marui, Junichiro; Tamano, Koichi; Sagara, Junichi; Dohmoto, Mitsuko; Oda, Ken; Ohshima, Eiji; Tachibana, Kuniharu; Higa, Yoshitaka; Ohashi, Shinichi; Koike, Hideaki; Machida, Masayuki

    2010-12-01

    Kojic acid is produced in large amounts by Aspergillus oryzae as a secondary metabolite and is widely used in the cosmetic industry. Glucose can be converted to kojic acid, perhaps by only a few steps, but no genes for the conversion have thus far been revealed. Using a DNA microarray, gene expression profiles under three pairs of conditions significantly affecting kojic acid production were compared. All genes were ranked using an index parameter reflecting both high amounts of transcription and a high induction ratio under producing conditions. After disruption of nine candidate genes selected from the top of the list, two genes of unknown function were found to be responsible for kojic acid biosynthesis, one having an oxidoreductase motif and the other a transporter motif. These two genes are closely associated in the genome, showing typical characteristics of genes involved in secondary metabolism. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Nominal versus Attained Weights in Universitas 21 Ranking

    Science.gov (United States)

    Soh, Kaycheng

    2014-01-01

    Universitas 21 Ranking of National Higher Education Systems (U21 Ranking) is one of the three new ranking systems appearing in 2012. In contrast with the other systems, U21 Ranking uses countries as the unit of analysis. It has several features which lend it with greater trustworthiness, but it also shared some methodological issues with the other…

  11. A Nuclear Ribosomal DNA Phylogeny of Acer Inferred with Maximum Likelihood, Splits Graphs, and Motif Analysis of 606 Sequences

    Directory of Open Access Journals (Sweden)

    Guido W. Grimm

    2006-01-01

    Full Text Available The multi-copy internal transcribed spacer (ITS region of nuclear ribosomal DNA is widely used to infer phylogenetic relationships among closely related taxa. Here we use maximum likelihood (ML and splits graph analyses to extract phylogenetic information from ~ 600 mostly cloned ITS sequences, representing 81 species and subspecies of Acer, and both species of its sister Dipteronia. Additional analyses compared sequence motifs in Acer and several hundred Anacardiaceae, Burseraceae, Meliaceae, Rutaceae, and Sapindaceae ITS sequences in GenBank. We also assessed the effects of using smaller data sets of consensus sequences with ambiguity coding (accounting for within-species variation instead of the full (partly redundant original sequences. Neighbor-nets and bipartition networks were used to visualize conflict among character state patterns. Species clusters observed in the trees and networks largely agree with morphology-based classifications; of de Jong’s (1994 16 sections, nine are supported in neighbor-net and bipartition networks, and ten by sequence motifs and the ML tree; of his 19 series, 14 are supported in networks, motifs, and the ML tree. Most nodes had higher bootstrap support with matrices of 105 or 40 consensus sequences than with the original matrix. Within-taxon ITS divergence did not differ between diploid and polyploid Acer, and there was little evidence of differentiated parental ITS haplotypes, suggesting that concerted evolution in Acer acts rapidly.

  12. A Nuclear Ribosomal DNA Phylogeny of Acer Inferred with Maximum Likelihood, Splits Graphs, and Motif Analysis of 606 Sequences

    Science.gov (United States)

    Grimm, Guido W.; Renner, Susanne S.; Stamatakis, Alexandros; Hemleben, Vera

    2007-01-01

    The multi-copy internal transcribed spacer (ITS) region of nuclear ribosomal DNA is widely used to infer phylogenetic relationships among closely related taxa. Here we use maximum likelihood (ML) and splits graph analyses to extract phylogenetic information from ~ 600 mostly cloned ITS sequences, representing 81 species and subspecies of Acer, and both species of its sister Dipteronia. Additional analyses compared sequence motifs in Acer and several hundred Anacardiaceae, Burseraceae, Meliaceae, Rutaceae, and Sapindaceae ITS sequences in GenBank. We also assessed the effects of using smaller data sets of consensus sequences with ambiguity coding (accounting for within-species variation) instead of the full (partly redundant) original sequences. Neighbor-nets and bipartition networks were used to visualize conflict among character state patterns. Species clusters observed in the trees and networks largely agree with morphology-based classifications; of de Jong’s (1994) 16 sections, nine are supported in neighbor-net and bipartition networks, and ten by sequence motifs and the ML tree; of his 19 series, 14 are supported in networks, motifs, and the ML tree. Most nodes had higher bootstrap support with matrices of 105 or 40 consensus sequences than with the original matrix. Within-taxon ITS divergence did not differ between diploid and polyploid Acer, and there was little evidence of differentiated parental ITS haplotypes, suggesting that concerted evolution in Acer acts rapidly. PMID:19455198

  13. A Comprehensive Analysis of Marketing Journal Rankings

    Science.gov (United States)

    Steward, Michelle D.; Lewis, Bruce R.

    2010-01-01

    The purpose of this study is to offer a comprehensive assessment of journal standings in Marketing from two perspectives. The discipline perspective of rankings is obtained from a collection of published journal ranking studies during the past 15 years. The studies in the published ranking stream are assessed for reliability by examining internal…

  14. Mutual Fund Tournament: Risk Taking Incentives Induced by Ranking Objectives

    OpenAIRE

    Goriaev, A.P.; Palomino, F.A.; Prat, A.

    2000-01-01

    There is now extensive empirical evidence showing that fund managers have relative performance objectives and adapt their investment strategy in the last part of the calendar year to their performance in the early part of the year. However, emphasis was put on returns in excess of some exogenous benchmark return.In this paper, we investigate whether fund managers have ranking objectives (as in a tournament).First, in a two-period model, we analyze the game played by two risk-neutral fund mana...

  15. The BiPublishers ranking: Main results and methodological problems when constructing rankings of academic publishers

    Directory of Open Access Journals (Sweden)

    Torres-Salinas, Daniel

    2015-12-01

    Full Text Available We present the results of the Bibliometric Indicators for Publishers project (also known as BiPublishers. This project represents the first attempt to systematically develop bibliometric publisher rankings. The data for this project was derived from the Book Citation Index and the study time period was 2009-2013. We have developed 42 rankings: 4 by fields and 38 by disciplines. We display six indicators for publishers divided into three types: output, impact and publisher’s profile. The aim is to capture different characteristics of the research performance of publishers. 254 publishers were processed and classified according to publisher type: commercial publishers and university presses. We present the main publishers by field and then discuss the principal challenges presented when developing this type of tool. The BiPublishers ranking is an on-going project which aims to develop and explore new data sources and indicators to better capture and define the research impact of publishers.Presentamos los resultados del proyecto Bibliometric Indicators for Publishers (BiPublishers. Es el primer proyecto que desarrolla de manera sistemática rankings bibliométricos de editoriales. La fuente de datos empleada es el Book Citation Index y el periodo de análisis 2009-2013. Se presentan 42 rankings: 4 por áreas y 38 por disciplinas. Mostramos seis indicadores por editorial divididos según su tipología: producción, impacto y características editoriales. Se procesaron 254 editoriales y se clasificaron según el tipo: comerciales y universitarias. Se presentan las principales editoriales por áreas. Después, se discuten los principales retos a superar en el desarrollo de este tipo de herramientas. El ranking Bipublishers es un proyecto en desarrollo que persigue analizar y explorar nuevas fuentes de datos e indicadores para captar y definir el impacto de las editoriales académicas.

  16. Ranking Spain's medical schools by their performance in the national residency examination.

    Science.gov (United States)

    Lopez-Valcarcel, B G; Ortún, V; Barber, P; Harris, J E; García, B

    2013-12-01

    Medical school graduates in Spain must take a uniform national exam (called "examen MIR") in order to enter postgraduate training in a specialty. Its results offer a unique opportunity to rank medical schools according to this exam. We measured differences in the MIR exam results among Spanish medical schools and assessed the stability of the MIR-based rankings for the period 2003-2011. In the year 2011 a total of 6873 residency positions nationwide were offered by the Spanish Ministry of Health, Social Services and Equality. These positions covered 47 specialties distributed over 231 training centers. A total of 11,550 medical graduates (including 1997 foreign graduates) took the MIR examination. Marked differences among medical schools were evident. The median graduate from medical school #1 and #29 occupied the positions 1477 and 5383, respectively. These figures correspond to a standardized ranking of 21 out of 100 for medical school #1 (that is, 1477/6873; half of medical school #1 obtained better [below position 21%] and half worse [over position 21%] results) and a standardized ranking of 70 out of 100 for medical school #29. While 81% of the medical school #1 graduates were amongst the best 3000 MIR exams and only 5% above the 5000 position the corresponding figures for medical school #29 graduates were 21% and 44%, respectively. The ranking position of the 29 medical schools was very stable between the years 2003 and 2011. There are marked differences in medical schools in Spain and these differences are very consistent over the years 2003-2011. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  17. PageRank in scale-free random graphs

    NARCIS (Netherlands)

    Chen, Ningyuan; Litvak, Nelli; Olvera-Cravioto, Mariana; Bonata, Anthony; Chung, Fan; Pralat, Paweł

    2014-01-01

    We analyze the distribution of PageRank on a directed configuration model and show that as the size of the graph grows to infinity, the PageRank of a randomly chosen node can be closely approximated by the PageRank of the root node of an appropriately constructed tree. This tree approximation is in

  18. 46 CFR 282.11 - Ranking of flags.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Ranking of flags. 282.11 Section 282.11 Shipping... COMMERCE OF THE UNITED STATES Foreign-Flag Competition § 282.11 Ranking of flags. The operators under each... priority of costs which are representative of the flag. For liner cargo vessels, the ranking of operators...

  19. Proteome-level assessment of origin, prevalence and function of Leucine-Aspartic Acid (LD) motifs

    KAUST Repository

    Alam, Tanvir; Alazmi, Meshari; Naser, Rayan Mohammad Mahmoud; Huser, Franceline; Momin, Afaque Ahmad Imtiyaz; Walkiewicz, Katarzyna Wiktoria; Canlas, Christian; Huser, Raphaë l; Ali, Amal J.; Merzaban, Jasmeen; Bajic, Vladimir B.; Gao, Xin; Arold, Stefan T.

    2018-01-01

    and migration, and revealed a new type of inverse LD motif consensus. Our evolutionary analysis suggested that LD motif signalling originated in the common unicellular ancestor of opisthokonts and amoebozoa by co-opting nuclear export sequences. Inter

  20. TOPDOM: database of conservatively located domains and motifs in proteins.

    Science.gov (United States)

    Varga, Julia; Dobson, László; Tusnády, Gábor E

    2016-09-01

    The TOPDOM database-originally created as a collection of domains and motifs located consistently on the same side of the membranes in α-helical transmembrane proteins-has been updated and extended by taking into consideration consistently localized domains and motifs in globular proteins, too. By taking advantage of the recently developed CCTOP algorithm to determine the type of a protein and predict topology in case of transmembrane proteins, and by applying a thorough search for domains and motifs as well as utilizing the most up-to-date version of all source databases, we managed to reach a 6-fold increase in the size of the whole database and a 2-fold increase in the number of transmembrane proteins. TOPDOM database is available at http://topdom.enzim.hu The webpage utilizes the common Apache, PHP5 and MySQL software to provide the user interface for accessing and searching the database. The database itself is generated on a high performance computer. tusnady.gabor@ttk.mta.hu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.