WorldWideScience

Sample records for active site prediction

  1. Earthquake prediction activities and Damavand earthquake precursor test site in Iran

    Science.gov (United States)

    Mokhtari, Mohammad

    2010-01-01

    Iran has long been known as one of the most seismically active areas of the world, and it frequently suffers destructive and catastrophic earthquakes that cause heavy loss of human life and widespread damage. The Alborz region in the northern part of Iran is an active EW trending mountain belt of 100 km wide and 600 km long. The Alborz range is bounded by the Talesh Mountains to the west and the Kopet Dagh Mountains to the east and consists of several sedimentary and volcanic layers of Cambrian to Eocene ages that were deformed during the late Cenozoic collision. Several active faults affect the central Alborz. The main active faults are the North Tehran and Mosha faults. The Mosha fault is one of the major active faults in the central Alborz as shown by its strong historical seismicity and its clear morphological signature. Situated in the vicinity of Tehran city, this 150-km-long N100° E trending fault represents an important potential seismic source. For earthquake monitoring and possible future prediction/precursory purposes, a test site has been established in the Alborz mountain region. The proximity to the capital of Iran with its high population density, low frequency but high magnitude earthquake occurrence, and active faults with their historical earthquake events have been considered as the main criteria for this selection. In addition, within the test site, there are hot springs and deep water wells that can be used for physico-chemical and radon gas analysis for earthquake precursory studies. The present activities include magnetic measurements; application of methodology for identification of seismogenic nodes for earthquakes of M ≥ 6.0 in the Alborz region developed by International Institute of Earthquake Prediction Theory and Mathematical Geophysics, IIEPT RAS, Russian Academy of Science, Moscow (IIEPT&MG RAS); a feasibility study using a dense seismic network for identification of future locations of seismic monitoring stations and application

  2. Prediction of P53 mutants (multiple sites transcriptional activity based on structural (2D&3D properties.

    Directory of Open Access Journals (Sweden)

    R Geetha Ramani

    Full Text Available Prediction of secondary site mutations that reinstate mutated p53 to normalcy has been the focus of intense research in the recent past owing to the fact that p53 mutants have been implicated in more than half of all human cancers and restoration of p53 causes tumor regression. However laboratory investigations are more often laborious and resource intensive but computational techniques could well surmount these drawbacks. In view of this, we formulated a novel approach utilizing computational techniques to predict the transcriptional activity of multiple site (one-site to five-site p53 mutants. The optimal MCC obtained by the proposed approach on prediction of one-site, two-site, three-site, four-site and five-site mutants were 0.775,0.341,0.784,0.916 and 0.655 respectively, the highest reported thus far in literature. We have also demonstrated that 2D and 3D features generate higher prediction accuracy of p53 activity and our findings revealed the optimal results for prediction of p53 status, reported till date. We believe detection of the secondary site mutations that suppress tumor growth may facilitate better understanding of the relationship between p53 structure and function and further knowledge on the molecular mechanisms and biological activity of p53, a targeted source for cancer therapy. We expect that our prediction methods and reported results may provide useful insights on p53 functional mechanisms and generate more avenues for utilizing computational techniques in biological data analysis.

  3. Homology models of dipeptidyl peptidases 8 and 9 with a focus on loop predictions near the active site.

    Science.gov (United States)

    Rummey, Christian; Metz, Günther

    2007-01-01

    Dipeptidyl peptidase 4 (DP4) inhibitors are currently under intensive investigation in late-stage clinical trials as a treatment for type II diabetes. Lack of selectivity toward the related enzymes DP8 and DP9 has recently emerged as a possible source of drug-induced toxicity. Unlike DP4, X-ray structures of DP8 and DP9 are not yet available. As an aid to understanding the structural basis for selectivity, the authors have constructed homology models of DP8 and DP9 based on the X-ray coordinates of DP4. Accurate sequence alignment reveals common structural features indicative for a well-preserved overall fold comprising two domains, namely, a hydrolase domain and a so-called beta-propeller, which together form the active site deeply buried within the protein. The conformation of two loops inside this deep cavity is particularly relevant for the active sites. The authors used a published protocol for loop prediction based on conformational sampling and energy analysis to generate plausible solutions for these two loops. The predictive power of the approach was successfully evaluated for the template protein DP4 and two additional known structures from the same protein family, namely, FAP and DPX. The authors also show that inclusion of the covalent ligand NVP-728 greatly enhances the refinement. Based on the established evaluation protocol, the corresponding loops of DP8 and DP9 were predicted and the resulting active sites were compared with DP4. In particular, the authors conclude that differences in the P2-pocket are relevant for the design of selective DP4 inhibitors. The loss of key interactions in DP8 and DP9 as predicted from their models is consistent with the selectivity profile of the DP4 clinical candidate MK-431.

  4. In Silico Structure Prediction of Human Fatty Acid Synthase-Dehydratase: A Plausible Model for Understanding Active Site Interactions.

    Science.gov (United States)

    John, Arun; Umashankar, Vetrivel; Samdani, A; Sangeetha, Manoharan; Krishnakumar, Subramanian; Deepa, Perinkulam Ravi

    2016-01-01

    Fatty acid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate β-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate-active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high-throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro.

  5. In Silico Structure Prediction of Human Fatty Acid Synthase-Dehydratase: A Plausible Model for Understanding Active Site Interactions.

    Science.gov (United States)

    John, Arun; Umashankar, Vetrivel; Samdani, A; Sangeetha, Manoharan; Krishnakumar, Subramanian; Deepa, Perinkulam Ravi

    2016-01-01

    Fatty acid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate β-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate-active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high-throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro. PMID:27559295

  6. SitesIdentify: a protein functional site prediction tool

    Directory of Open Access Journals (Sweden)

    Doig Andrew J

    2009-11-01

    Full Text Available Abstract Background The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function is useful in order to gain information about its potential role. There are many available approaches to predict functional site, but many are not made available via a publicly-accessible application. Results Here we present a functional site prediction tool (SitesIdentify, based on combining sequence conservation information with geometry-based cleft identification, that is freely available via a web-server. We have shown that SitesIdentify compares favourably to other functional site prediction tools in a comparison of seven methods on a non-redundant set of 237 enzymes with annotated active sites. Conclusion SitesIdentify is able to produce comparable accuracy in predicting functional sites to its closest available counterpart, but in addition achieves improved accuracy for proteins with few characterised homologues. SitesIdentify is available via a webserver at http://www.manchester.ac.uk/bioinformatics/sitesidentify/

  7. LRRK2 Kinase Activity and Biology are Not Uniformly Predicted by its Autophosphorylation and Cellular Phosphorylation Site Status

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    April eReynolds

    2014-06-01

    Full Text Available Missense mutations in the Leucine Rich Repeat protein Kinase 2 (LRRK2 gene are the most common genetic predisposition to develop Parkinson’s disease (PD LRRK2 is a large multi-domain phosphoprotein with a GTPase domain and a serine/threonine protein kinase domain whose activity is implicated in neuronal toxicity; however the precise mechanism is unknown. LRRK2 autophosphorylates on several serine/threonine residues across the enzyme and is found constitutively phosphorylated on Ser910, Ser935, Ser955 and Ser973, which are proposed to be regulated by upstream kinases. Here we investigate the phosphoregulation at these sites by analyzing the effects of disease-associated mutations Arg1441Cys, Arg1441Gly, Ala1442Pro, Tyr1699Cys, Ile2012Thr, Gly2019Ser, and Ile2020Thr. We also studied alanine substitutions of phosphosite serines 910, 935, 955 and 973 and specific LRRK2 inhibition on autophosphorylation of LRRK2 Ser1292, Thr1491, Thr2483 and phosphorylation at the cellular sites. We found that mutants in the Roc-COR domains, including Arg1441Cys, Arg1441His, Ala1442Pro and Tyr1699Cys, can positively enhance LRRK2 kinase activity while concomitantly inducing the dephosphorylation of the cellular sites. Mutation of the cellular sites individually did not affect LRRK2 intrinsic kinase activity; however, Ser910/935/955/973Ala mutations trended toward increased kinase activity of LRRK2. Increased cAMP levels did not lead to increased LRRK2 cellular site phosphorylation, 14-3-3 binding or kinase activity. In cells, inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser1292 by Calyculin A and okadaic acid sensitive phosphatases, while the cellular sites are dephosphorylated by Calyculin A sensitive phosphatases. These findings indicate that comparative analysis of both Ser1292 and Ser910/935/955/973 phosphorylation sites will provide important and distinct measures of LRRK2 kinase and biological activity in vitro and in vivo.

  8. Habitat composition and connectivity predicts bat presence and activity at foraging sites in a large UK conurbation.

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    James D Hale

    Full Text Available BACKGROUND: Urbanization is characterized by high levels of sealed land-cover, and small, geometrically complex, fragmented land-use patches. The extent and density of urbanized land-use is increasing, with implications for habitat quality, connectivity and city ecology. Little is known about densification thresholds for urban ecosystem function, and the response of mammals, nocturnal and cryptic taxa are poorly studied in this respect. Bats (Chiroptera are sensitive to changing urban form at a species, guild and community level, so are ideal model organisms for analyses of this nature. METHODOLOGY/PRINCIPAL FINDINGS: We surveyed bats around urban ponds in the West Midlands conurbation, United Kingdom (UK. Sites were stratified between five urban land classes, representing a gradient of built land-cover at the 1 km(2 scale. Models for bat presence and activity were developed using land-cover and land-use data from multiple radii around each pond. Structural connectivity of tree networks was used as an indicator of the functional connectivity between habitats. All species were sensitive to measures of urban density. Some were also sensitive to landscape composition and structural connectivity at different spatial scales. These results represent new findings for an urban area. The activity of Pipistrellus pipistrellus (Schreber 1774 exhibited a non-linear relationship with the area of built land-cover, being much reduced beyond the threshold of ∼60% built surface. The presence of tree networks appears to mitigate the negative effects of urbanization for this species. CONCLUSIONS/SIGNIFICANCE: Our results suggest that increasing urban density negatively impacts the study species. This has implications for infill development policy, built density targets and the compact city debate. Bats were also sensitive to the composition and structure of the urban form at a range of spatial scales, with implications for land-use planning and management

  9. Probabilistic prediction models for aggregate quarry siting

    Science.gov (United States)

    Robinson, G.R.; Larkins, P.M.

    2007-01-01

    Weights-of-evidence (WofE) and logistic regression techniques were used in a GIS framework to predict the spatial likelihood (prospectivity) of crushed-stone aggregate quarry development. The joint conditional probability models, based on geology, transportation network, and population density variables, were defined using quarry location and time of development data for the New England States, North Carolina, and South Carolina, USA. The Quarry Operation models describe the distribution of active aggregate quarries, independent of the date of opening. The New Quarry models describe the distribution of aggregate quarries when they open. Because of the small number of new quarries developed in the study areas during the last decade, independent New Quarry models have low parameter estimate reliability. The performance of parameter estimates derived for Quarry Operation models, defined by a larger number of active quarries in the study areas, were tested and evaluated to predict the spatial likelihood of new quarry development. Population density conditions at the time of new quarry development were used to modify the population density variable in the Quarry Operation models to apply to new quarry development sites. The Quarry Operation parameters derived for the New England study area, Carolina study area, and the combined New England and Carolina study areas were all similar in magnitude and relative strength. The Quarry Operation model parameters, using the modified population density variables, were found to be a good predictor of new quarry locations. Both the aggregate industry and the land management community can use the model approach to target areas for more detailed site evaluation for quarry location. The models can be revised easily to reflect actual or anticipated changes in transportation and population features. ?? International Association for Mathematical Geology 2007.

  10. Text mining improves prediction of protein functional sites.

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    Karin M Verspoor

    Full Text Available We present an approach that integrates protein structure analysis and text mining for protein functional site prediction, called LEAP-FS (Literature Enhanced Automated Prediction of Functional Sites. The structure analysis was carried out using Dynamics Perturbation Analysis (DPA, which predicts functional sites at control points where interactions greatly perturb protein vibrations. The text mining extracts mentions of residues in the literature, and predicts that residues mentioned are functionally important. We assessed the significance of each of these methods by analyzing their performance in finding known functional sites (specifically, small-molecule binding sites and catalytic sites in about 100,000 publicly available protein structures. The DPA predictions recapitulated many of the functional site annotations and preferentially recovered binding sites annotated as biologically relevant vs. those annotated as potentially spurious. The text-based predictions were also substantially supported by the functional site annotations: compared to other residues, residues mentioned in text were roughly six times more likely to be found in a functional site. The overlap of predictions with annotations improved when the text-based and structure-based methods agreed. Our analysis also yielded new high-quality predictions of many functional site residues that were not catalogued in the curated data sources we inspected. We conclude that both DPA and text mining independently provide valuable high-throughput protein functional site predictions, and that integrating the two methods using LEAP-FS further improves the quality of these predictions.

  11. High precision prediction of functional sites in protein structures.

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    Ljubomir Buturovic

    Full Text Available We address the problem of assigning biological function to solved protein structures. Computational tools play a critical role in identifying potential active sites and informing screening decisions for further lab analysis. A critical parameter in the practical application of computational methods is the precision, or positive predictive value. Precision measures the level of confidence the user should have in a particular computed functional assignment. Low precision annotations lead to futile laboratory investigations and waste scarce research resources. In this paper we describe an advanced version of the protein function annotation system FEATURE, which achieved 99% precision and average recall of 95% across 20 representative functional sites. The system uses a Support Vector Machine classifier operating on the microenvironment of physicochemical features around an amino acid. We also compared performance of our method with state-of-the-art sequence-level annotator Pfam in terms of precision, recall and localization. To our knowledge, no other functional site annotator has been rigorously evaluated against these key criteria. The software and predictive models are incorporated into the WebFEATURE service at http://feature.stanford.edu/wf4.0-beta.

  12. SVM-based prediction of caspase substrate cleavage sites

    OpenAIRE

    Wee, Lawrence JK; Tan, Tin Wee; Ranganathan, Shoba

    2006-01-01

    Background Caspases belong to a class of cysteine proteases which function as critical effectors in apoptosis and inflammation by cleaving substrates immediately after unique sites. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. Recently, different computational methods have been developed to predict the cleavage sites of caspase substrates with varying degrees of success. As the support vector...

  13. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    CERN Document Server

    Amor, Benjamin R C; Yaliraki, Sophia N; Barahona, Mauricio

    2016-01-01

    Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for identifying allosteric sites and the mediating interactions that connect them to the active site. Using an atomistic graph with edges weighted by covalent and non-covalent bond energies, we obtain a bond-to-bond propensity that quantifies the effect of instantaneous bond fluctuations propagating through the protein. We use this propensity to detect the sites and communication pathways most strongly linked to the active site, assessing their significance through quantile regression and comparison against a reference set of 100 generic proteins. We exemplify our method in detail with three well-studied allosteric proteins: caspase-1, CheY, and h-Ras, correctly predicting the location of the allosteric site and identifying key allosteric interactions. Consistent prediction of...

  14. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data from a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating using predictive computational...

  15. Sequence- and structure-based prediction of eukaryotic proteinphosphorylation sites

    DEFF Research Database (Denmark)

    Blom, Nikolaj; Gammeltoft, Steen; Brunak, Søren

    1999-01-01

    Protein phosphorylation at serine, threonine or tyrosine residues affects a multitude of cellular signaling processes. Howis specificity in substrate recognition and phosphorylation by protein kinases achieved? Here, we present an artificialneural network method that predicts phosphorylation site...

  16. Two Predicted Transmembrane Domains Exclude Very Long Chain Fatty acyl-CoAs from the Active Site of Mouse Wax Synthase.

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    Steffen Kawelke

    Full Text Available Wax esters are used as coatings or storage lipids in all kingdoms of life. They are synthesized from a fatty alcohol and an acyl-CoA by wax synthases. In order to get insights into the structure-function relationships of a wax synthase from Mus musculus, a domain swap experiment between the mouse acyl-CoA:wax alcohol acyltransferase (AWAT2 and the homologous mouse acyl-CoA:diacylglycerol O-acyltransferase 2 (DGAT2 was performed. This showed that the substrate specificity of AWAT2 is partially determined by two predicted transmembrane domains near the amino terminus of AWAT2. Upon exchange of the two domains for the respective part of DGAT2, the resulting chimeric enzyme was capable of incorporating up to 20% of very long acyl chains in the wax esters upon expression in S. cerevisiae strain H1246. The amount of very long acyl chains in wax esters synthesized by wild type AWAT2 was negligible. The effect was narrowed down to a single amino acid position within one of the predicted membrane domains, the AWAT2 N36R variant. Taken together, we provide first evidence that two predicted transmembrane domains in AWAT2 are involved in determining its acyl chain length specificity.

  17. Flood Predictions Combining Regional and Single Site Hydrometric Information

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    Campos–Aranda

    2010-07-01

    Full Text Available Initially, the statistic benefit of flood predictions obtained by combining reliable regional and scarce site hydrometric data is pointed out. Then the mathematical equations for combining mean and standard deviation logarithms of regional and site data are exposed, as well as the necessary expressions for desired predictions, based on Student's t distribution. Later two numerical applications are described, the first one based in Carrizal hydrometric station located in Santiago River in Nayarit and the second one which makes use of five water gauging stations in Tempoal River in Veracruz. Finally, a conclusion is formulated pointing out the simplicity of that method and the accuracy of its predictions.

  18. The Binding Mode Prediction and Similar Ligand Potency in the Active Site of Vitamin D Receptor with QM/MM Interaction, MESP, and MD Simulation.

    Science.gov (United States)

    Selvaraman, Nagamani; Selvam, Saravana Kumar; Muthusamy, Karthikeyan

    2016-08-01

    Non-secosteroidal ligands are well-known vitamin D receptor (VDR) agonists. In this study, we described a combined QM/MM to define the protein-ligand interaction energy a strong positive correlation in both QM-MM interaction energy and binding free energy against the biological activity. The molecular dynamics simulation study was performed, and specific interactions were extensively studied. The molecular docking results and surface analysis shed light on steric and electrostatic complementarities of these non-secosteroidal ligands to VDR. Finally, the drug likeness properties were also calculated and found within the acceptable range. The results show that bulky group substitutions in side chain decrease the VDR activity, whereas a small substitution increased it. Functional analyses of H393A and H301A mutations substantiate their roles in the VDR agonistic and antagonistic activities. Apart from the His393 and His301, two other amino acids in the hinge region viz. Ser233 and Arg270 acted as an electron donor/acceptor specific to the agonist in the distinct ligand potency. The results from this study disclose the binding mechanism of VDR agonists and structural modifications required to improve the selectivity.

  19. The Binding Mode Prediction and Similar Ligand Potency in the Active Site of Vitamin D Receptor with QM/MM Interaction, MESP, and MD Simulation.

    Science.gov (United States)

    Selvaraman, Nagamani; Selvam, Saravana Kumar; Muthusamy, Karthikeyan

    2016-08-01

    Non-secosteroidal ligands are well-known vitamin D receptor (VDR) agonists. In this study, we described a combined QM/MM to define the protein-ligand interaction energy a strong positive correlation in both QM-MM interaction energy and binding free energy against the biological activity. The molecular dynamics simulation study was performed, and specific interactions were extensively studied. The molecular docking results and surface analysis shed light on steric and electrostatic complementarities of these non-secosteroidal ligands to VDR. Finally, the drug likeness properties were also calculated and found within the acceptable range. The results show that bulky group substitutions in side chain decrease the VDR activity, whereas a small substitution increased it. Functional analyses of H393A and H301A mutations substantiate their roles in the VDR agonistic and antagonistic activities. Apart from the His393 and His301, two other amino acids in the hinge region viz. Ser233 and Arg270 acted as an electron donor/acceptor specific to the agonist in the distinct ligand potency. The results from this study disclose the binding mechanism of VDR agonists and structural modifications required to improve the selectivity. PMID:26945790

  20. A systems biology approach to transcription factor binding site prediction.

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    Xiang Zhou

    Full Text Available BACKGROUND: The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates. METHODOLOGY/PRINCIPAL FINDINGS: We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data. CONCLUSIONS/SIGNIFICANCE: Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct

  1. Glycosylation site prediction using ensembles of Support Vector Machine classifiers

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    Silvescu Adrian

    2007-11-01

    Full Text Available Abstract Background Glycosylation is one of the most complex post-translational modifications (PTMs of proteins in eukaryotic cells. Glycosylation plays an important role in biological processes ranging from protein folding and subcellular localization, to ligand recognition and cell-cell interactions. Experimental identification of glycosylation sites is expensive and laborious. Hence, there is significant interest in the development of computational methods for reliable prediction of glycosylation sites from amino acid sequences. Results We explore machine learning methods for training classifiers to predict the amino acid residues that are likely to be glycosylated using information derived from the target amino acid residue and its sequence neighbors. We compare the performance of Support Vector Machine classifiers and ensembles of Support Vector Machine classifiers trained on a dataset of experimentally determined N-linked, O-linked, and C-linked glycosylation sites extracted from O-GlycBase version 6.00, a database of 242 proteins from several different species. The results of our experiments show that the ensembles of Support Vector Machine classifiers outperform single Support Vector Machine classifiers on the problem of predicting glycosylation sites in terms of a range of standard measures for comparing the performance of classifiers. The resulting methods have been implemented in EnsembleGly, a web server for glycosylation site prediction. Conclusion Ensembles of Support Vector Machine classifiers offer an accurate and reliable approach to automated identification of putative glycosylation sites in glycoprotein sequences.

  2. Prediction of PK-specific phosphorylation site based on information entropy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Phosphorylation is a crucial way to control the activity of proteins in many eukaryotic organisms in vivo. Experimental methods to determine phosphorylation sites in substrates are usually restricted by the in vitro condition of enzymes and very intensive in time and labor. Although some in silico methods and web servers have been introduced for automatic detection of phosphorylation sites, sophisticated methods are still in urgent demand to further improve prediction performances. Protein primary se-quences can help predict phosphorylation sites catalyzed by different protein kinase and most com-putational approaches use a short local peptide to make prediction. However, the useful information may be lost if only the conservative residues that are not close to the phosphorylation site are consid-ered in prediction, which would hamper the prediction results. A novel prediction method named IEPP (Information-Entropy based Phosphorylation Prediction) is presented in this paper for automatic de-tection of potential phosphorylation sites. In prediction, the sites around the phosphorylation sites are selected or excluded by their entropy values. The algorithm was compared with other methods such as GSP and PPSP on the ABL, MAPK and PKA PK families. The superior prediction accuracies were ob-tained in various measurements such as sensitivity (Sn) and specificity (Sp). Furthermore, compared with some online prediction web servers on the new discovered phosphorylation sites, IEPP also yielded the best performance. IEPP is another useful computational resource for identification of PK-specific phosphorylation sites and it also has the advantages of simpleness, efficiency and con-venience.

  3. Predicting web site audience demographics for web advertising targeting using multi-web site clickstream data

    OpenAIRE

    Bock, K W; D. VAN DEN POEL; S. MANIGART

    2009-01-01

    Several recent studies have explored the virtues of behavioral targeting and personalization for online advertising. In this paper, we add to this literature by proposing a cost-effective methodology for the prediction of demographic web site visitor profiles that can be used for web advertising targeting purposes. The methodology involves the transformation of web site visitors’ clickstream patterns to a set of features and the training of Random Forest classifiers that generate predictions ...

  4. Fast dynamics perturbation analysis for prediction of protein functional sites

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    Cohn Judith D

    2008-01-01

    Full Text Available Abstract Background We present a fast version of the dynamics perturbation analysis (DPA algorithm to predict functional sites in protein structures. The original DPA algorithm finds regions in proteins where interactions cause a large change in the protein conformational distribution, as measured using the relative entropy Dx. Such regions are associated with functional sites. Results The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that Dx in a normal-modes model is highly correlated with an entropic term that only depends on the eigenvalues of the normal modes. The eigenvalues are accurately estimated using first-order perturbation theory, resulting in a N-fold reduction in the overall computational requirements of the algorithm, where N is the number of residues in the protein. The performance of the original and Fast DPA algorithms was compared using protein structures from a standard small-molecule docking test set. For nominal implementations of each algorithm, top-ranked Fast DPA predictions overlapped the true binding site 94% of the time, compared to 87% of the time for original DPA. In addition, per-protein recall statistics (fraction of binding-site residues that are among predicted residues were slightly better for Fast DPA. On the other hand, per-protein precision statistics (fraction of predicted residues that are among binding-site residues were slightly better using original DPA. Overall, the performance of Fast DPA in predicting ligand-binding-site residues was comparable to that of the original DPA algorithm. Conclusion Compared to the original DPA algorithm, the decreased run time with comparable performance makes Fast DPA well-suited for implementation on a web server and for high-throughput analysis.

  5. An Overview of the Prediction of Protein DNA-Binding Sites

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    Jingna Si

    2015-03-01

    Full Text Available Interactions between proteins and DNA play an important role in many essential biological processes such as DNA replication, transcription, splicing, and repair. The identification of amino acid residues involved in DNA-binding sites is critical for understanding the mechanism of these biological activities. In the last decade, numerous computational approaches have been developed to predict protein DNA-binding sites based on protein sequence and/or structural information, which play an important role in complementing experimental strategies. At this time, approaches can be divided into three categories: sequence-based DNA-binding site prediction, structure-based DNA-binding site prediction, and homology modeling and threading. In this article, we review existing research on computational methods to predict protein DNA-binding sites, which includes data sets, various residue sequence/structural features, machine learning methods for comparison and selection, evaluation methods, performance comparison of different tools, and future directions in protein DNA-binding site prediction. In particular, we detail the meta-analysis of protein DNA-binding sites. We also propose specific implications that are likely to result in novel prediction methods, increased performance, or practical applications.

  6. Efficient oxygen electrocatalysis on special active sites

    DEFF Research Database (Denmark)

    Halck, Niels Bendtsen

    is used to explain the increase in activity observed for the OER catalyst ruthenium dioxide when it is mixed with nickel or cobalt. Manganese and cobalt oxides when in the vicinity of gold also display an increase in OER activity which can be explained by locally created special active sites. Density...

  7. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site...

  8. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

  9. Computational Prediction of RNA-Binding Proteins and Binding Sites.

    Science.gov (United States)

    Si, Jingna; Cui, Jing; Cheng, Jin; Wu, Rongling

    2015-01-01

    Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%-8% of all proteins are RNA-binding proteins (RBPs). Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein-RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein-RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  10. Computational Prediction of RNA-Binding Proteins and Binding Sites

    Directory of Open Access Journals (Sweden)

    Jingna Si

    2015-11-01

    Full Text Available Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%–8% of all proteins are RNA-binding proteins (RBPs. Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein–RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein–RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  11. Characterization of Reuse Activities at Contaminated Sites

    OpenAIRE

    Angela Vitulli; Charlotte Dougherty; Kimberly Bosworth

    2004-01-01

    Given the increased focus on reuse activity within EPA and state site cleanup programs, policy makers would benefit from looking across programs to better understand the extent and nature of reuse; examine site characteristics that influence reuse; leverage lessons learned; and coordinate reuse activities, data collection, and information management. This research paper begins to examine these issues. It reports the results of a preliminary review and analysis of available EPA and state progr...

  12. Fingerprinting differential active site constraints of ATPases

    OpenAIRE

    Hacker, Stephan M.; Hardt, Norman; Buntru, Alexander; Pagliarini, Dana; Möckel, Martin; Mayer, Thomas U; Scheffner, Martin; Hauck, Christof R.; Marx, Andreas

    2013-01-01

    The free energy provided by adenosine triphosphate (ATP) hydrolysis is central to many cellular processes and, therefore, the number of enzymes utilizing ATP as a substrate is almost innumerable. Modified analogues of ATP are a valuable means to understand the biological function of ATPases. Although these enzymes have evolved towards binding to ATP, large differences in active site architectures were found. In order to systematically access the specific active site constraints of different A...

  13. Glycosylation site prediction using ensembles of Support Vector Machine classifiers

    OpenAIRE

    Silvescu Adrian; Sinapov Jivko; Caragea Cornelia; Dobbs Drena; Honavar Vasant

    2007-01-01

    Abstract Background Glycosylation is one of the most complex post-translational modifications (PTMs) of proteins in eukaryotic cells. Glycosylation plays an important role in biological processes ranging from protein folding and subcellular localization, to ligand recognition and cell-cell interactions. Experimental identification of glycosylation sites is expensive and laborious. Hence, there is significant interest in the development of computational methods for reliable prediction of glyco...

  14. SITE-DIRECTED MUTAGENESIS OF PROPOSED ACTIVE-SITE RESIDUES OF PENICILLIN-BINDING PROTEIN-5 FROM ESCHERICHIA-COLI

    NARCIS (Netherlands)

    VANDERLINDEN, MPG; DEHAAN, L; DIDEBERG, O; KECK, W

    1994-01-01

    Alignment of the amino acid sequence of penicillin-binding protein 5 (PBP5) with the sequences of other members of the family of active-site-serine penicillin-interacting enzymes predicted the residues playing a role in the catalytic mechanism of PBP5. Apart from the active-site (Ser(44)), Lys(47),

  15. Seismic Hazard Assessment in Site Evaluation for Nuclear Installations: Ground Motion Prediction Equations and Site Response

    International Nuclear Information System (INIS)

    The objective of this publication is to provide the state-of-the-art practice and detailed technical elements related to ground motion evaluation by ground motion prediction equations (GMPEs) and site response in the context of seismic hazard assessments as recommended in IAEA Safety Standards Series No. SSG-9, Seismic Hazards in Site Evaluation for Nuclear Installations. The publication includes the basics of GMPEs, ground motion simulation, selection and adjustment of GMPEs, site characterization, and modelling of site response in order to improve seismic hazard assessment. The text aims at delineating the most important aspects of these topics (including current practices, criticalities and open problems) within a coherent framework. In particular, attention has been devoted to filling conceptual gaps. It is written as a reference text for trained users who are responsible for planning preparatory seismic hazard analyses for siting of all nuclear installations and/or providing constraints for anti-seismic design and retrofitting of existing structures

  16. MetWAMer: eukaryotic translation initiation site prediction

    Directory of Open Access Journals (Sweden)

    Brendel Volker

    2008-09-01

    Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.

  17. Activity Prediction: A Twitter-based Exploration

    OpenAIRE

    Weerkamp, W.; Rijke, de, M.

    2012-01-01

    Social media platforms allow users to share their messages with everyone else. In microblogs, e.g., Twitter, people mostly report on what they did, they talk about current activities, and mention things they plan to do in the near future. In this paper, we propose the task of activity prediction, that is, trying to establish a set of activities that are likely to become popular at a later time. We perform a small-scale initial experiment, in which we try to predict popular activities for the ...

  18. Dynamo theory prediction of solar activity

    Science.gov (United States)

    Schatten, Kenneth H.

    1988-01-01

    The dynamo theory technique to predict decadal time scale solar activity variations is introduced. The technique was developed following puzzling correlations involved with geomagnetic precursors of solar activity. Based upon this, a dynamo theory method was developed to predict solar activity. The method was used successfully in solar cycle 21 by Schatten, Scherrer, Svalgaard, and Wilcox, after testing with 8 prior solar cycles. Schatten and Sofia used the technique to predict an exceptionally large cycle, peaking early (in 1990) with a sunspot value near 170, likely the second largest on record. Sunspot numbers are increasing, suggesting that: (1) a large cycle is developing, and (2) that the cycle may even surpass the largest cycle (19). A Sporer Butterfly method shows that the cycle can now be expected to peak in the latter half of 1989, consistent with an amplitude comparable to the value predicted near the last solar minimum.

  19. Performance prediction for Grid workflow activities based on features-ranked RBF network

    Institute of Scientific and Technical Information of China (English)

    Wang Jie; Duan Rubing; Farrukh Nadeem

    2009-01-01

    Accurate performance prediction of Grid workflow activities can help Grid schedulers map activities to appropriate Grid sites. This paper describes an approach based on features-ranked RBF neural network to predict the performance of Grid workflow activities. Experimental results for two kinds of real world Grid workflow activities are presented to show effectiveness of our approach.

  20. Method of predicting Splice Sites based on signal interactions

    Directory of Open Access Journals (Sweden)

    Deogun Jitender S

    2006-04-01

    Full Text Available Abstract Background Predicting and proper ranking of canonical splice sites (SSs is a challenging problem in bioinformatics and machine learning communities. Any progress in SSs recognition will lead to better understanding of splicing mechanism. We introduce several new approaches of combining a priori knowledge for improved SS detection. First, we design our new Bayesian SS sensor based on oligonucleotide counting. To further enhance prediction quality, we applied our new de novo motif detection tool MHMMotif to intronic ends and exons. We combine elements found with sensor information using Naive Bayesian Network, as implemented in our new tool SpliceScan. Results According to our tests, the Bayesian sensor outperforms the contemporary Maximum Entropy sensor for 5' SS detection. We report a number of putative Exonic (ESE and Intronic (ISE Splicing Enhancers found by MHMMotif tool. T-test statistics on mouse/rat intronic alignments indicates, that detected elements are on average more conserved as compared to other oligos, which supports our assumption of their functional importance. The tool has been shown to outperform the SpliceView, GeneSplicer, NNSplice, Genio and NetUTR tools for the test set of human genes. SpliceScan outperforms all contemporary ab initio gene structural prediction tools on the set of 5' UTR gene fragments. Conclusion Designed methods have many attractive properties, compared to existing approaches. Bayesian sensor, MHMMotif program and SpliceScan tools are freely available on our web site. Reviewers This article was reviewed by Manyuan Long, Arcady Mushegian and Mikhail Gelfand.

  1. Better estimation of protein-DNA interaction parameters improve prediction of functional sites

    Directory of Open Access Journals (Sweden)

    O'Flanagan Ruadhan A

    2008-12-01

    Full Text Available Abstract Background Characterizing transcription factor binding motifs is a common bioinformatics task. For transcription factors with variable binding sites, we need to get many suboptimal binding sites in our training dataset to get accurate estimates of free energy penalties for deviating from the consensus DNA sequence. One procedure to do that involves a modified SELEX (Systematic Evolution of Ligands by Exponential Enrichment method designed to produce many such sequences. Results We analyzed low stringency SELEX data for E. coli Catabolic Activator Protein (CAP, and we show here that appropriate quantitative analysis improves our ability to predict in vitro affinity. To obtain large number of sequences required for this analysis we used a SELEX SAGE protocol developed by Roulet et al. The sequences obtained from here were subjected to bioinformatic analysis. The resulting bioinformatic model characterizes the sequence specificity of the protein more accurately than those sequence specificities predicted from previous analysis just by using a few known binding sites available in the literature. The consequences of this increase in accuracy for prediction of in vivo binding sites (and especially functional ones in the E. coli genome are also discussed. We measured the dissociation constants of several putative CAP binding sites by EMSA (Electrophoretic Mobility Shift Assay and compared the affinities to the bioinformatics scores provided by methods like the weight matrix method and QPMEME (Quadratic Programming Method of Energy Matrix Estimation trained on known binding sites as well as on the new sites from SELEX SAGE data. We also checked predicted genome sites for conservation in the related species S. typhimurium. We found that bioinformatics scores based on SELEX SAGE data does better in terms of prediction of physical binding energies as well as in detecting functional sites. Conclusion We think that training binding site detection

  2. Can one predict DNA Transcription Start Sites by studying bubbles?

    CERN Document Server

    Van Erp, T S; Hagmann, J G; Peyrard, M

    2005-01-01

    It has been speculated that bubble formation of several base-pairs due to thermal fluctuations is indicatory for biological active sites. Recent evidence, based on experiments and molecular dynamics (MD) simulations using the Peyrard-Bishop-Dauxois model, seems to point in this direction. However, sufficiently large bubbles appear only seldom which makes an accurate calculation difficult even for minimal models. In this letter, we introduce a new method that is orders of magnitude faster than MD. Using this method we are able to show that the present evidence is unsubstantiated.

  3. BET is active on Sellafield site

    International Nuclear Information System (INIS)

    Several companies, all part of BET Plant Services are carrying out work at the British Nuclear Fuels (BNFL) site at Sellafield, Cumbria, on one of the largest construction projects in Europe. The main development scheme is the THORP (Thermal Oxide Reprocessing Plant) buildings. One of the BET companies has the contract to paint the inside of the fuel storage ponds. It will also coat the surfaces of the MASWEP (Medium Active Solid Waste Encapsulation Plant) complex. Other work includes insulation and fire prevention installation. Scaffolding at the EARP (Enhanced Actinide Removal Plant) site is being provided on a common user basis so all the contractors can use the scaffolding and share the cost. Temporary office and living accommodation blocks have been provide by another BET company. (author)

  4. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    Science.gov (United States)

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-08-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

  5. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    Science.gov (United States)

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-01-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID:27561351

  6. Prediction of fine-tuned promoter activity from DNA sequence.

    Science.gov (United States)

    Siwo, Geoffrey; Rider, Andrew; Tan, Asako; Pinapati, Richard; Emrich, Scott; Chawla, Nitesh; Ferdig, Michael

    2016-01-01

    The quantitative prediction of transcriptional activity of genes using promoter sequence is fundamental to the engineering of biological systems for industrial purposes and understanding the natural variation in gene expression. To catalyze the development of new algorithms for this purpose, the Dialogue on Reverse Engineering Assessment and Methods (DREAM) organized a community challenge seeking predictive models of promoter activity given normalized promoter activity data for 90 ribosomal protein promoters driving expression of a fluorescent reporter gene. By developing an unbiased modeling approach that performs an iterative search for predictive DNA sequence features using the frequencies of various k-mers, inferred DNA mechanical properties and spatial positions of promoter sequences, we achieved the best performer status in this challenge. The specific predictive features used in the model included the frequency of the nucleotide G, the length of polymeric tracts of T and TA, the frequencies of 6 distinct trinucleotides and 12 tetranucleotides, and the predicted protein deformability of the DNA sequence. Our method accurately predicted the activity of 20 natural variants of ribosomal protein promoters (Spearman correlation r = 0.73) as compared to 33 laboratory-mutated variants of the promoters (r = 0.57) in a test set that was hidden from participants. Notably, our model differed substantially from the rest in 2 main ways: i) it did not explicitly utilize transcription factor binding information implying that subtle DNA sequence features are highly associated with gene expression, and ii) it was entirely based on features extracted exclusively from the 100 bp region upstream from the translational start site demonstrating that this region encodes much of the overall promoter activity. The findings from this study have important implications for the engineering of predictable gene expression systems and the evolution of gene expression in naturally occurring

  7. CERAPP: Collaborative estrogen receptor activity prediction project

    DEFF Research Database (Denmark)

    Mansouri, Kamel; Abdelaziz, Ahmed; Rybacka, Aleksandra;

    2016-01-01

    Background: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER......). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. oBjectives: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project......) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. Methods: CERAPP combined multiple models developed in collaboration with 17 groups in the United...

  8. Prediction of flow and drawdown for the site characterization and validation site in the Stripa mine

    International Nuclear Information System (INIS)

    Geophysical and hydrologic data from a location in the Stripa mine in Sweden, called the Site Characterization and Validation (SCV) block, has been used to create a series of models for flow through the fracture network. The models can be characterized as 'equivalent discontinuum' models. Equivalent discontinuum models are derived starting from a specified lattice or 'template'. An inverse analysis called 'simulated annealing' is used to make a random search through the elements of the lattice to find a configuration that can reproduce the measured responses. Evidence at Stripa points to hydrology which is dominated by fracture zones. These have been identified and located through extensive characterization efforts. Lattice templates were arranged to lie on the fracture zones identified by Black and Olsson. The fundamental goal of this project was to build a fracture flow model based on an initial data set, and use this model to make predictions of the flow behavior during a new test. Then given data from the new test, predict a second test, etc. The first data set was an interference test called C1-2. Both a two-dimensional and a three-dimensional model were annealed to the C1-2 data and use this model to predict the behavior of the Simulated Drift Experiment (SDE). The SDE measured the flow into, and drawdown due to reducing the pressure in a group of 6 parallel boreholes. Then both the C1-2 and SDE data were used to predict the flow into a drawdown due to an excavation, the Validation Drift (VD), made through the boreholes. Finally, all the data was used to predict the hydrologic response to opening another hole, T1. Annealing to the C1-2 test gave an excellent prediction of the SDE. The VD effects were dominated by near-field physics that were not predictable. However, the calculations and measurements could be used to postulate that a dramatic decrease in hydraulic conductivity near the drift was due to degassing of nitrogen as the inflowing water was

  9. Prediction of nucleosome positioning based on transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Xianfu Yi

    Full Text Available BACKGROUND: The DNA of all eukaryotic organisms is packaged into nucleosomes, the basic repeating units of chromatin. The nucleosome consists of a histone octamer around which a DNA core is wrapped and the linker histone H1, which is associated with linker DNA. By altering the accessibility of DNA sequences, the nucleosome has profound effects on all DNA-dependent processes. Understanding the factors that influence nucleosome positioning is of great importance for the study of genomic control mechanisms. Transcription factors (TFs have been suggested to play a role in nucleosome positioning in vivo. PRINCIPAL FINDINGS: Here, the minimum redundancy maximum relevance (mRMR feature selection algorithm, the nearest neighbor algorithm (NNA, and the incremental feature selection (IFS method were used to identify the most important TFs that either favor or inhibit nucleosome positioning by analyzing the numbers of transcription factor binding sites (TFBSs in 53,021 nucleosomal DNA sequences and 50,299 linker DNA sequences. A total of nine important families of TFs were extracted from 35 families, and the overall prediction accuracy was 87.4% as evaluated by the jackknife cross-validation test. CONCLUSIONS: Our results are consistent with the notion that TFs are more likely to bind linker DNA sequences than the sequences in the nucleosomes. In addition, our results imply that there may be some TFs that are important for nucleosome positioning but that play an insignificant role in discriminating nucleosome-forming DNA sequences from nucleosome-inhibiting DNA sequences. The hypothesis that TFs play a role in nucleosome positioning is, thus, confirmed by the results of this study.

  10. Prediction control of active power filters

    Institute of Scientific and Technical Information of China (English)

    王莉娜; 罗安

    2003-01-01

    A prediction method to obtain harmonic reference for active power filter is presented. It is a new use ofthe adaptive predictive filter based on FIR. The delay inherent in digital controller is successfully compensated by u-sing the proposed method, and the computing load is not very large compared with the conventional method. Moreo-ver, no additional hardware is needed. Its DSP-based realization is also presented, which is characterized by time-va-riant rate sampling, quasi synchronous sampling, and synchronous operation among the line frequency, PWM gener-ating and sampling in A/D unit. Synchronous operation releases the limitation on PWM modulation ratio and guar-antees that the electrical noises resulting from the switching operation of IGBTs do not interfere with the sampledcurrent. The simulation and experimental results verify the satisfactory performance of the proposed method.

  11. Establishing a predictive maintenance program at the Hanford Site

    International Nuclear Information System (INIS)

    This document contains information about a new Predictive Maintenance Program being developed and implemented at the Hanford Reservation. Details of the document include: background on persons developing the program, history of predictive maintenance, implementation of new program, engineering task analysis, network development and new software, issues to be resolved, benefits expected, and appendix gives information about the symposium from which this paper is based

  12. Computational prediction of cAMP receptor protein (CRP) binding sites in cyanobacterial genomes

    Science.gov (United States)

    Xu, Minli; Su, Zhengchang

    2009-01-01

    Background Cyclic AMP receptor protein (CRP), also known as catabolite gene activator protein (CAP), is an important transcriptional regulator widely distributed in many bacteria. The biological processes under the regulation of CRP are highly diverse among different groups of bacterial species. Elucidation of CRP regulons in cyanobacteria will further our understanding of the physiology and ecology of this important group of microorganisms. Previously, CRP has been experimentally studied in only two cyanobacterial strains: Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120; therefore, a systematic genome-scale study of the potential CRP target genes and binding sites in cyanobacterial genomes is urgently needed. Results We have predicted and analyzed the CRP binding sites and regulons in 12 sequenced cyanobacterial genomes using a highly effective cis-regulatory binding site scanning algorithm. Our results show that cyanobacterial CRP binding sites are very similar to those in E. coli; however, the regulons are very different from that of E. coli. Furthermore, CRP regulons in different cyanobacterial species/ecotypes are also highly diversified, ranging from photosynthesis, carbon fixation and nitrogen assimilation, to chemotaxis and signal transduction. In addition, our prediction indicates that crp genes in modern cyanobacteria are likely inherited from a common ancestral gene in their last common ancestor, and have adapted various cellular functions in different environments, while some cyanobacteria lost their crp genes as well as CRP binding sites during the course of evolution. Conclusion The CRP regulons in cyanobacteria are highly diversified, probably as a result of divergent evolution to adapt to various ecological niches. Cyanobacterial CRPs may function as lineage-specific regulators participating in various cellular processes, and are important in some lineages. However, they are dispensable in some other lineages. The loss of CRPs in these species

  13. Computational prediction of cAMP receptor protein (CRP binding sites in cyanobacterial genomes

    Directory of Open Access Journals (Sweden)

    Su Zhengchang

    2009-01-01

    Full Text Available Abstract Background Cyclic AMP receptor protein (CRP, also known as catabolite gene activator protein (CAP, is an important transcriptional regulator widely distributed in many bacteria. The biological processes under the regulation of CRP are highly diverse among different groups of bacterial species. Elucidation of CRP regulons in cyanobacteria will further our understanding of the physiology and ecology of this important group of microorganisms. Previously, CRP has been experimentally studied in only two cyanobacterial strains: Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120; therefore, a systematic genome-scale study of the potential CRP target genes and binding sites in cyanobacterial genomes is urgently needed. Results We have predicted and analyzed the CRP binding sites and regulons in 12 sequenced cyanobacterial genomes using a highly effective cis-regulatory binding site scanning algorithm. Our results show that cyanobacterial CRP binding sites are very similar to those in E. coli; however, the regulons are very different from that of E. coli. Furthermore, CRP regulons in different cyanobacterial species/ecotypes are also highly diversified, ranging from photosynthesis, carbon fixation and nitrogen assimilation, to chemotaxis and signal transduction. In addition, our prediction indicates that crp genes in modern cyanobacteria are likely inherited from a common ancestral gene in their last common ancestor, and have adapted various cellular functions in different environments, while some cyanobacteria lost their crp genes as well as CRP binding sites during the course of evolution. Conclusion The CRP regulons in cyanobacteria are highly diversified, probably as a result of divergent evolution to adapt to various ecological niches. Cyanobacterial CRPs may function as lineage-specific regulators participating in various cellular processes, and are important in some lineages. However, they are dispensable in some other lineages. The

  14. Study the active site of flavonoid applying radiation chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Wu Jilan; Sun Gang; Zhang Fugen; He Yongke; Li Jiuqiang [Department of Technical Physics, Peking Univ., Beijing (China)

    2000-03-01

    Flavonoid are a large and important class of naturally occurring, low molecular weight benzo-{gamma}-pyrone derivatives which are reported to have a myriad of biological activities, but the study on the active sites of flavonoids is still ambiguous. In this paper, rutin, quercetin and baicalin have been selected as model compounds. It is well known that rutin is used in inhibiting arteriosclerosis and baicalin is antibacterial and antiviral. They have similar basic structure, but their medicinal properties are so different, why? As most flavonoids contain carbonyl group, which can capture electron effectively, we predict that flavonoids can capture electron to form radical anion. The formation of anion radical may have influence on the mitochondrial electron transport chain. The difference in the ability of forming anion radical may cause the difference in their medicinal effects. (author)

  15. SSFinder: High Throughput CRISPR-Cas Target Sites Prediction Tool

    OpenAIRE

    Santosh Kumar Upadhyay; Shailesh Sharma

    2014-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system facilitates targeted genome editing in organisms. Despite high demand of this system, finding a reliable tool for the determination of specific target sites in large genomic data remained challenging. Here, we report SSFinder, a python script to perform high throughput detection of specific target sites in large nucleotide datasets. The SSFinder is a user-friendly tool, compatible wit...

  16. Predicting functional sites with an automated algorithm suitable for heterogeneous datasets

    Directory of Open Access Journals (Sweden)

    Livesay Dennis R

    2005-05-01

    Full Text Available Abstract Background In a previous report (La et al., Proteins, 2005, we have demonstrated that the identification of phylogenetic motifs, protein sequence fragments conserving the overall familial phylogeny, represent a promising approach for sequence/function annotation. Across a structurally and functionally heterogeneous dataset, phylogenetic motifs have been demonstrated to correspond to a wide variety of functional site archetypes, including those defined by surface loops, active site clefts, and less exposed regions. However, in our original demonstration of the technique, phylogenetic motif identification is dependent upon a manually determined similarity threshold, prohibiting large-scale application of the technique. Results In this report, we present an algorithmic approach that determines thresholds without human subjectivity. The approach relies on significant raw data preprocessing to improve signal detection. Subsequently, Partition Around Medoids Clustering (PAMC of the similarity scores assesses sequence fragments where functional annotation remains in question. The accuracy of the approach is confirmed through comparisons to our previous (manual results and structural analyses. Triosephosphate isomerase and arginyl-tRNA synthetase are discussed as exemplar cases. A quantitative functional site prediction assessment algorithm indicates that the phylogenetic motif predictions, which require sequence information only, are nearly as good as those from evolutionary trace methods that do incorporate structure. Conclusion The automated threshold detection algorithm has been incorporated into MINER, our web-based phylogenetic motif identification server. MINER is freely available on the web at http://www.pmap.csupomona.edu/MINER/. Pre-calculated functional site predictions of the COG database and an implementation of the threshold detection algorithm, in the R statistical language, can also be accessed at the website.

  17. A Mechanism-Based Model for the Prediction of the Metabolic Sites of Steroids Mediated by Cytochrome P450 3A4

    Directory of Open Access Journals (Sweden)

    Zi-Ru Dai

    2015-06-01

    Full Text Available Early prediction of xenobiotic metabolism is essential for drug discovery and development. As the most important human drug-metabolizing enzyme, cytochrome P450 3A4 has a large active cavity and metabolizes a broad spectrum of substrates. The poor substrate specificity of CYP3A4 makes it a huge challenge to predict the metabolic site(s on its substrates. This study aimed to develop a mechanism-based prediction model based on two key parameters, including the binding conformation and the reaction activity of ligands, which could reveal the process of real metabolic reaction(s and the site(s of modification. The newly established model was applied to predict the metabolic site(s of steroids; a class of CYP3A4-preferred substrates. 38 steroids and 12 non-steroids were randomly divided into training and test sets. Two major metabolic reactions, including aliphatic hydroxylation and N-dealkylation, were involved in this study. At least one of the top three predicted metabolic sites was validated by the experimental data. The overall accuracy for the training and test were 82.14% and 86.36%, respectively. In summary, a mechanism-based prediction model was established for the first time, which could be used to predict the metabolic site(s of CYP3A4 on steroids with high predictive accuracy.

  18. Prediction of protein hydration sites from sequence by modular neural networks

    DEFF Research Database (Denmark)

    Ehrlich, L.; Reczko, M.; Bohr, Henrik;

    1998-01-01

    The hydration properties of a protein are important determinants of its structure and function. Here, modular neural networks are employed to predict ordered hydration sites using protein sequence information. First, secondary structure and solvent accessibility are predicted from sequence with t...... provide insight into the mutual interdependencies between the location of ordered water sites and the structural and chemical characteristics of the protein residues.......The hydration properties of a protein are important determinants of its structure and function. Here, modular neural networks are employed to predict ordered hydration sites using protein sequence information. First, secondary structure and solvent accessibility are predicted from sequence with two...... structure and solvent accessibility and, using actual values of these properties, redidue hydration can be predicted to 77% accuracy with a Metthews coefficient of 0.43. However, predicted property data with an accuracy of 60-70% result in less than half the improvement in predictive performance observed...

  19. Bivalent-like chromatin markers are predictive for transcription start site distribution in human.

    Directory of Open Access Journals (Sweden)

    Zhihua Zhang

    Full Text Available Deep sequencing of 5' capped transcripts has revealed a variety of transcription initiation patterns, from narrow, focused promoters to wide, broad promoters. Attempts have already been made to model empirically classified patterns, but virtually no quantitative models for transcription initiation have been reported. Even though both genetic and epigenetic elements have been associated with such patterns, the organization of regulatory elements is largely unknown. Here, linear regression models were derived from a pool of regulatory elements, including genomic DNA features, nucleosome organization, and histone modifications, to predict the distribution of transcription start sites (TSS. Importantly, models including both active and repressive histone modification markers, e.g. H3K4me3 and H4K20me1, were consistently found to be much more predictive than models with only single-type histone modification markers, indicating the possibility of "bivalent-like" epigenetic control of transcription initiation. The nucleosome positions are proposed to be coded in the active component of such bivalent-like histone modification markers. Finally, we demonstrated that models trained on one cell type could successfully predict TSS distribution in other cell types, suggesting that these models may have a broader application range.

  20. RADIOLYTIC HYDROGEN GENERATION INSAVANNAH RIVER SITE (SRS) HIGH LEVEL WASTETANKS COMPARISON OF SRS AND HANFORDMODELING PREDICTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, C; Ned Bibler, N

    2009-04-15

    In the high level waste tanks at the Savannah River Site (SRS), hydrogen is produced continuously by interaction of the radiation in the tank with water in the waste. Consequently, the vapor spaces of the tanks are purged to prevent the accumulation of H{sub 2} and possible formation of a flammable mixture in a tank. Personnel at SRS have developed an empirical model to predict the rate of H{sub 2} formation in a tank. The basis of this model is the prediction of the G value for H{sub 2} production. This G value is the number of H{sub 2} molecules produced per 100 eV of radiolytic energy absorbed by the waste. Based on experimental studies it was found that the G value for H{sub 2} production from beta radiation and from gamma radiation were essentially equal. The G value for H{sub 2} production from alpha radiation was somewhat higher. Thus, the model has two equations, one for beta/gamma radiation and one for alpha radiation. Experimental studies have also indicated that both G values are decreased by the presence of nitrate and nitrite ions in the waste. These are the main scavengers for the precursors of H{sub 2} in the waste; thus the equations that were developed predict G values for hydrogen production as a function of the concentrations of these two ions in waste. Knowing the beta/gamma and alpha heat loads in the waste allows one to predict the total generation rate for hydrogen in a tank. With this prediction a ventilation rate can be established for each tank to ensure that a flammable mixture is not formed in the vapor space in a tank. Recently personnel at Hanford have developed a slightly different model for predicting hydrogen G values. Their model includes the same precursor for H{sub 2} as the SRS model but also includes an additional precursor not in the SRS model. Including the second precursor for H{sub 2} leads to different empirical equations for predicting the G values for H{sub 2} as a function of the nitrate and nitrite concentrations in

  1. DAPPLE 2: a Tool for the Homology-Based Prediction of Post-Translational Modification Sites.

    Science.gov (United States)

    Trost, Brett; Maleki, Farhad; Kusalik, Anthony; Napper, Scott

    2016-08-01

    The post-translational modification of proteins is critical for regulating their function. Although many post-translational modification sites have been experimentally determined, particularly in certain model organisms, experimental knowledge of these sites is severely lacking for many species. Thus, it is important to be able to predict sites of post-translational modification in such species. Previously, we described DAPPLE, a tool that facilitates the homology-based prediction of one particular post-translational modification, phosphorylation, in an organism of interest using known phosphorylation sites from other organisms. Here, we describe DAPPLE 2, which expands and improves upon DAPPLE in three major ways. First, it predicts sites for many post-translational modifications (20 different types) using data from several sources (15 online databases). Second, it has the ability to make predictions approximately 2-7 times faster than DAPPLE depending on the database size and the organism of interest. Third, it simplifies and accelerates the process of selecting predicted sites of interest by categorizing them based on gene ontology terms, keywords, and signaling pathways. We show that DAPPLE 2 can successfully predict known human post-translational modification sites using, as input, known sites from species that are either closely (e.g., mouse) or distantly (e.g., yeast) related to humans. DAPPLE 2 can be accessed at http://saphire.usask.ca/saphire/dapple2 . PMID:27367363

  2. Crystallographic B factor of critical residues at enzyme active site

    Institute of Scientific and Technical Information of China (English)

    张海龙; 宋时英; 林政炯

    1999-01-01

    Thirty-seven sets of crystallographic enzyme data were selected from Protein Data Bank (PDB, 1995). The average temperature factors (B) of the critical residues at the active site and the whole molecule of those enzymes were calculated respectively. The statistical results showed that the critical residues at the active site of most of the enzymes had lower B factors than did the whole molecules, indicating that in the crystalline state the critical residues at the active site of the natural enzymes possess more stable conformation than do the whole molecules. The flexibility of the active site during the unfolding by denaturing was also discussed.

  3. A computational approach for prediction of donor splice sites with improved accuracy.

    Science.gov (United States)

    Meher, Prabina Kumar; Sahu, Tanmaya Kumar; Rao, A R; Wahi, S D

    2016-09-01

    Identification of splice sites is important due to their key role in predicting the exon-intron structure of protein coding genes. Though several approaches have been developed for the prediction of splice sites, further improvement in the prediction accuracy will help predict gene structure more accurately. This paper presents a computational approach for prediction of donor splice sites with higher accuracy. In this approach, true and false splice sites were first encoded into numeric vectors and then used as input in artificial neural network (ANN), support vector machine (SVM) and random forest (RF) for prediction. ANN and SVM were found to perform equally and better than RF, while tested on HS3D and NN269 datasets. Further, the performance of ANN, SVM and RF were analyzed by using an independent test set of 50 genes and found that the prediction accuracy of ANN was higher than that of SVM and RF. All the predictors achieved higher accuracy while compared with the existing methods like NNsplice, MEM, MDD, WMM, MM1, FSPLICE, GeneID and ASSP, using the independent test set. We have also developed an online prediction server (PreDOSS) available at http://cabgrid.res.in:8080/predoss, for prediction of donor splice sites using the proposed approach. PMID:27302911

  4. The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction.

    Science.gov (United States)

    Roche, Daniel B; Buenavista, Maria T; Tetchner, Stuart J; McGuffin, Liam J

    2011-07-01

    The IntFOLD server is a novel independent server that integrates several cutting edge methods for the prediction of structure and function from sequence. Our guiding principles behind the server development were as follows: (i) to provide a simple unified resource that makes our prediction software accessible to all and (ii) to produce integrated output for predictions that can be easily interpreted. The output for predictions is presented as a simple table that summarizes all results graphically via plots and annotated 3D models. The raw machine readable data files for each set of predictions are also provided for developers, which comply with the Critical Assessment of Methods for Protein Structure Prediction (CASP) data standards. The server comprises an integrated suite of five novel methods: nFOLD4, for tertiary structure prediction; ModFOLD 3.0, for model quality assessment; DISOclust 2.0, for disorder prediction; DomFOLD 2.0 for domain prediction; and FunFOLD 1.0, for ligand binding site prediction. Predictions from the IntFOLD server were found to be competitive in several categories in the recent CASP9 experiment. The IntFOLD server is available at the following web site: http://www.reading.ac.uk/bioinf/IntFOLD/.

  5. Savannah River Site prioritization of transition activities

    International Nuclear Information System (INIS)

    Effective management of SRS conversion from primarily a production facility to other missions (or Decontamination and Decommissioning (D ampersand D)) requires a systematic and consistent method of prioritizing the transition activities. This report discusses the design of a prioritizing method developed to achieve systematic and consistent methods of prioritizing these activities

  6. Savannah River Site prioritization of transition activities

    Energy Technology Data Exchange (ETDEWEB)

    Finley, R.H.

    1993-11-01

    Effective management of SRS conversion from primarily a production facility to other missions (or Decontamination and Decommissioning (D&D)) requires a systematic and consistent method of prioritizing the transition activities. This report discusses the design of a prioritizing method developed to achieve systematic and consistent methods of prioritizing these activities.

  7. Safety Oversight of Decommissioning Activities at DOE Nuclear Sites

    International Nuclear Information System (INIS)

    The Defense Nuclear Facilities Safety Board (Board) is an independent federal agency established by Congress in 1988 to provide nuclear safety oversight of activities at U.S. Department of Energy (DOE) defense nuclear facilities. The activities under the Board's jurisdiction include the design, construction, startup, operation, and decommissioning of defense nuclear facilities at DOE sites. This paper reviews the Board's safety oversight of decommissioning activities at DOE sites, identifies the safety problems observed, and discusses Board initiatives to improve the safety of decommissioning activities at DOE sites. The decommissioning of former defense nuclear facilities has reduced the risk of radioactive material contamination and exposure to the public and site workers. In general, efforts to perform decommissioning work at DOE defense nuclear sites have been successful, and contractors performing decommissioning work have a good safety record. Decommissioning activities have recently been completed at sites identified for closure, including the Rocky Flats Environmental Technology Site, the Fernald Closure Project, and the Miamisburg Closure Project (the Mound site). The Rocky Flats and Fernald sites, which produced plutonium parts and uranium materials for defense needs (respectively), have been turned into wildlife refuges. The Mound site, which performed R and D activities on nuclear materials, has been converted into an industrial and technology park called the Mound Advanced Technology Center. The DOE Office of Legacy Management is responsible for the long term stewardship of these former EM sites. The Board has reviewed many decommissioning activities, and noted that there are valuable lessons learned that can benefit both DOE and the contractor. As part of its ongoing safety oversight responsibilities, the Board and its staff will continue to review the safety of DOE and contractor decommissioning activities at DOE defense nuclear sites

  8. Conserved functional motifs and homology modelling to predict hidden moonlighting functional sites

    Directory of Open Access Journals (Sweden)

    Helen R Irving

    2015-06-01

    Full Text Available Moonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here we review how hidden moonlighting functional centers which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico which in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.

  9. Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites

    KAUST Repository

    Wong, Aloysius Tze

    2015-06-09

    Moonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here, we review how hidden moonlighting functional centers, which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico, which, in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.

  10. The balance of flexibility and rigidity in the active site residues of hen egg white lysozyme

    Institute of Scientific and Technical Information of China (English)

    Qi Jian-Xun; Jiang Fan

    2011-01-01

    The crystallographic temperature factors (B factor) of individual atoms contain important information about the thermal motion of the atoms in a macromolecule. Previously the theory of flexibility of active site has been established based on the observation that the enzyme activity is sensitive to low concentration denaturing agents. It has been found that the loss of enzyme activity occurs well before the disruption of the three-dimensional structural scaffold of the enzyme. To test the theory of conformational flexibility of enzyme active site, crystal structures were perturbed by soaking in low concentration guanidine hydrochloride solutions. It was found that many lysozyme crystals tested could still diffract until the concentration of guanidine hydrochloride reached 3 M. It was also found that the B factors averaged over individually collected data sets were more accurate. Thus it suggested that accurate measurement of crystal temperature factors could be achieved for medium-high or even medium resolution crystals by averaging over multiple data sets. Furthermore, we found that the correctly predicted active sites included not only the more flexible residues, but also some more rigid residues. Both the flexible and the rigid residues in the active site played an important role in forming the active site residue network, covering the majority of the substrate binding residues. Therefore, this experimental prediction method may be useful for characterizing the binding site and the function of a protein, such as drug targeting.

  11. Identification of promiscuous ene-reductase activity by mining structural databases using active site constellations.

    Science.gov (United States)

    Steinkellner, Georg; Gruber, Christian C; Pavkov-Keller, Tea; Binter, Alexandra; Steiner, Kerstin; Winkler, Christoph; Lyskowski, Andrzej; Schwamberger, Orsolya; Oberer, Monika; Schwab, Helmut; Faber, Kurt; Macheroux, Peter; Gruber, Karl

    2014-01-01

    The exploitation of catalytic promiscuity and the application of de novo design have recently opened the access to novel, non-natural enzymatic activities. Here we describe a structural bioinformatic method for predicting catalytic activities of enzymes based on three-dimensional constellations of functional groups in active sites ('catalophores'). As a proof-of-concept we identify two enzymes with predicted promiscuous ene-reductase activity (reduction of activated C-C double bonds) and compare them with known ene-reductases, that is, members of the Old Yellow Enzyme family. Despite completely different amino acid sequences, overall structures and protein folds, high-resolution crystal structures reveal equivalent binding modes of typical Old Yellow Enzyme substrates and ligands. Biochemical and biocatalytic data show that the two enzymes indeed possess ene-reductase activity and reveal an inverted stereopreference compared with Old Yellow Enzymes for some substrates. This method could thus be a tool for the identification of viable starting points for the development and engineering of novel biocatalysts. PMID:24954722

  12. NetPhosYeast: prediction of protein phosphorylation sites in yeast

    DEFF Research Database (Denmark)

    Ingrell, C.R.; Miller, Martin Lee; Jensen, O.N.;

    2007-01-01

    We here present a neural network-based method for the prediction of protein phosphorylation sites in yeast-an important model organism for basic research. Existing protein phosphorylation site predictors are primarily based on mammalian data and show reduced sensitivity on yeast phosphorylation...... sites compared to those in humans, suggesting the need for an yeast-specific phosphorylation site predictor. NetPhosYeast achieves a correlation coefficient close to 0.75 with a sensitivity of 0.84 and specificity of 0.90 and outperforms existing predictors in the identification of phosphorylation sites...... in yeast....

  13. Ensemble approach combining multiple methods improves human transcription start site prediction.

    LENUS (Irish Health Repository)

    Dineen, David G

    2010-01-01

    The computational prediction of transcription start sites is an important unsolved problem. Some recent progress has been made, but many promoters, particularly those not associated with CpG islands, are still difficult to locate using current methods. These methods use different features and training sets, along with a variety of machine learning techniques and result in different prediction sets.

  14. Prediction of Human Activity by Discovering Temporal Sequence Patterns.

    Science.gov (United States)

    Li, Kang; Fu, Yun

    2014-08-01

    Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units. PMID:26353344

  15. Genome-wide prediction, display and refinement of binding sites with information theory-based models

    Directory of Open Access Journals (Sweden)

    Leeder J Steven

    2003-09-01

    Full Text Available Abstract Background We present Delila-genome, a software system for identification, visualization and analysis of protein binding sites in complete genome sequences. Binding sites are predicted by scanning genomic sequences with information theory-based (or user-defined weight matrices. Matrices are refined by adding experimentally-defined binding sites to published binding sites. Delila-Genome was used to examine the accuracy of individual information contents of binding sites detected with refined matrices as a measure of the strengths of the corresponding protein-nucleic acid interactions. The software can then be used to predict novel sites by rescanning the genome with the refined matrices. Results Parameters for genome scans are entered using a Java-based GUI interface and backend scripts in Perl. Multi-processor CPU load-sharing minimized the average response time for scans of different chromosomes. Scans of human genome assemblies required 4–6 hours for transcription factor binding sites and 10–19 hours for splice sites, respectively, on 24- and 3-node Mosix and Beowulf clusters. Individual binding sites are displayed either as high-resolution sequence walkers or in low-resolution custom tracks in the UCSC genome browser. For large datasets, we applied a data reduction strategy that limited displays of binding sites exceeding a threshold information content to specific chromosomal regions within or adjacent to genes. An HTML document is produced listing binding sites ranked by binding site strength or chromosomal location hyperlinked to the UCSC custom track, other annotation databases and binding site sequences. Post-genome scan tools parse binding site annotations of selected chromosome intervals and compare the results of genome scans using different weight matrices. Comparisons of multiple genome scans can display binding sites that are unique to each scan and identify sites with significantly altered binding strengths

  16. Using site-specific soil samples as a substitution for improved hydrological and nonpoint source predictions.

    Science.gov (United States)

    Chen, Lei; Wang, Guobo; Zhong, Yucen; Zhao, Xin; Shen, Zhenyao

    2016-08-01

    Soil databases are one of the most important inputs for watershed models, and the quality of soil properties affects how well a model performs. The objectives of this study were to (1) quantify the sensitivity of model outputs to soil properties and to (2) use site-specific soil properties as a substitution for more accurate hydrological and nonpoint source (H/NPS) predictions. Soil samples were collected from a typical mountainous watershed in China, and the impacts of soil sample parameters on H/NPS predictions were quantified using the Soil and Water Assessment Tool (SWAT). The most sensitive parameters related to predicting flow, sediment, and total phosphorus (TP) mainly were the soil hydrological, the channel erosion processes, and the initial soil chemical environment, respectively. When the site-specific soil properties were used, the uncertainties (coefficient of variation) related to predicting the hydrology, sediment and TP decreased by 75∼80 %, 75∼84 %, and 46∼61 %, respectively. Based on changes in the Nash-Sutcliff coefficient, the model performance improved by 4.9 and 19.45 % for the hydrological and sediment model, accordingly. However, site-specific soil properties did not contribute to better TP predictions because of the high spatial variability of the soil P concentrations across the large watershed. Thus, although site-specific soil samples can be used to obtain more accurate H/NPS predictions, more sampling sites are required to apply this method in large watersheds.

  17. Using site-specific soil samples as a substitution for improved hydrological and nonpoint source predictions.

    Science.gov (United States)

    Chen, Lei; Wang, Guobo; Zhong, Yucen; Zhao, Xin; Shen, Zhenyao

    2016-08-01

    Soil databases are one of the most important inputs for watershed models, and the quality of soil properties affects how well a model performs. The objectives of this study were to (1) quantify the sensitivity of model outputs to soil properties and to (2) use site-specific soil properties as a substitution for more accurate hydrological and nonpoint source (H/NPS) predictions. Soil samples were collected from a typical mountainous watershed in China, and the impacts of soil sample parameters on H/NPS predictions were quantified using the Soil and Water Assessment Tool (SWAT). The most sensitive parameters related to predicting flow, sediment, and total phosphorus (TP) mainly were the soil hydrological, the channel erosion processes, and the initial soil chemical environment, respectively. When the site-specific soil properties were used, the uncertainties (coefficient of variation) related to predicting the hydrology, sediment and TP decreased by 75∼80 %, 75∼84 %, and 46∼61 %, respectively. Based on changes in the Nash-Sutcliff coefficient, the model performance improved by 4.9 and 19.45 % for the hydrological and sediment model, accordingly. However, site-specific soil properties did not contribute to better TP predictions because of the high spatial variability of the soil P concentrations across the large watershed. Thus, although site-specific soil samples can be used to obtain more accurate H/NPS predictions, more sampling sites are required to apply this method in large watersheds. PMID:27146539

  18. The Surface Groups and Active Site of Fibrous Mineral Materials

    Institute of Scientific and Technical Information of China (English)

    DONG Fa-qin; WAN Pu; FENG Qi-ming; SONG Gong-bao; PENG Tong-jiang; LI Ping; LI Guo-wu

    2004-01-01

    The exposed and transformed groups of fibrous brucite,wollastonite,chrysotile asbestos,sepiolite,palygorskite,clinoptilolite,crocidolite and diatomaceous earth mineral materials are analyzed by IR spectra after acid and alikali etching,strong mechanical and polarity molecular interaction.The results show the active sites concentrate on the ends in stick mineral materials and on the defect or hole edge in pipe mineral materials.The inside active site of mineral materials plays a main role in small molecular substance.The shape of minerals influence their distribution and density of active site.The strong mechanical impulsion and weak chemical force change the active site feature of minerals,the powder process enables minerals exposed more surface group and more combined types.The surface processing with the small polarity molecular or the brand of middle molecular may produce ionation and new coordinate bond,and change the active properties and level of original mineral materials.

  19. TarPmiR: a new approach for microRNA target site prediction

    Science.gov (United States)

    Ding, Jun; Li, Xiaoman; Hu, Haiyan

    2016-01-01

    Motivation: The identification of microRNA (miRNA) target sites is fundamentally important for studying gene regulation. There are dozens of computational methods available for miRNA target site prediction. Despite their existence, we still cannot reliably identify miRNA target sites, partially due to our limited understanding of the characteristics of miRNA target sites. The recently published CLASH (crosslinking ligation and sequencing of hybrids) data provide an unprecedented opportunity to study the characteristics of miRNA target sites and improve miRNA target site prediction methods. Results: Applying four different machine learning approaches to the CLASH data, we identified seven new features of miRNA target sites. Combining these new features with those commonly used by existing miRNA target prediction algorithms, we developed an approach called TarPmiR for miRNA target site prediction. Testing on two human and one mouse non-CLASH datasets, we showed that TarPmiR predicted more than 74.2% of true miRNA target sites in each dataset. Compared with three existing approaches, we demonstrated that TarPmiR is superior to these existing approaches in terms of better recall and better precision. Availability and Implementation: The TarPmiR software is freely available at http://hulab.ucf.edu/research/projects/miRNA/TarPmiR/. Contacts: haihu@cs.ucf.edu or xiaoman@mail.ucf.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27207945

  20. RNA:(guanine-N2 methyltransferases RsmC/RsmD and their homologs revisited – bioinformatic analysis and prediction of the active site based on the uncharacterized Mj0882 protein structure

    Directory of Open Access Journals (Sweden)

    Rychlewski Leszek

    2002-04-01

    Full Text Available Abstract Background Escherichia coli guanine-N2 (m2G methyltransferases (MTases RsmC and RsmD modify nucleosides G1207 and G966 of 16S rRNA. They possess a common MTase domain in the C-terminus and a variable region in the N-terminus. Their C-terminal domain is related to the YbiN family of hypothetical MTases, but nothing is known about the structure or function of the N-terminal domain. Results Using a combination of sequence database searches and fold recognition methods it has been demonstrated that the N-termini of RsmC and RsmD are related to each other and that they represent a "degenerated" version of the C-terminal MTase domain. Novel members of the YbiN family from Archaea and Eukaryota were also indentified. It is inferred that YbiN and both domains of RsmC and RsmD are closely related to a family of putative MTases from Gram-positive bacteria and Archaea, typified by the Mj0882 protein from M. jannaschii (1dus in PDB. Based on the results of sequence analysis and structure prediction, the residues involved in cofactor binding, target recognition and catalysis were identified, and the mechanism of the guanine-N2 methyltransfer reaction was proposed. Conclusions Using the known Mj0882 structure, a comprehensive analysis of sequence-structure-function relationships in the family of genuine and putative m2G MTases was performed. The results provide novel insight into the mechanism of m2G methylation and will serve as a platform for experimental analysis of numerous uncharacterized N-MTases.

  1. Predicting Polymerase Ⅱ Core Promoters by Cooperating Transcription Factor Binding Sites in Eukaryotic Genes

    Institute of Scientific and Technical Information of China (English)

    Xiao-Tu MA; Min-Ping QIAN; Hai-Xu TANG

    2004-01-01

    Several discriminate functions for predicting core promoters that based on the potential cooperation between transcription factor binding sites (TFBSs) are discussed. It is demonstrated that the promoter predicting accuracy is improved when the cooperation among TFBSs is taken into consideration.The core promoter region of a newly discovered gene CKLFSF1 is predicted to locate more than 1.5 kb far away from the 5′ end of the transcript and in the last intron of its upstream gene, which is experimentally confirmed later. The core promoters of 3402 human RefSeq sequences, obtained by extending the mRNAs in human genome sequences, are predicted by our algorithm, and there are about 60% of the predicted core promoters locating within the ± 500 bp region relative to the annotated transcription start site.

  2. Cell-type specificity of ChIP-predicted transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Håndstad Tony

    2012-08-01

    Full Text Available Abstract Background Context-dependent transcription factor (TF binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding? Results We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity. Conclusions Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.

  3. Regression applied to protein binding site prediction and comparison with classification

    Directory of Open Access Journals (Sweden)

    Gala Jean-Luc

    2009-09-01

    Full Text Available Abstract Background The structural genomics centers provide hundreds of protein structures of unknown function. Therefore, developing methods enabling the determination of a protein function automatically is imperative. The determination of a protein function can be achieved by studying the network of its physical interactions. In this context, identifying a potential binding site between proteins is of primary interest. In the literature, methods for predicting a potential binding site location generally are based on classification tools. The aim of this paper is to show that regression tools are more efficient than classification tools for patches based binding site predictors. For this purpose, we developed a patches based binding site localization method usable with either regression or classification tools. Results We compared predictive performances of regression tools with performances of machine learning classifiers. Using leave-one-out cross-validation, we showed that regression tools provide better predictions than classification ones. Among regression tools, Multilayer Perceptron ranked highest in the quality of predictions. We compared also the predictive performance of our patches based method using Multilayer Perceptron with the performance of three other methods usable through a web server. Our method performed similarly to the other methods. Conclusion Regression is more efficient than classification when applied to our binding site localization method. When it is possible, using regression instead of classification for other existing binding site predictors will probably improve results. Furthermore, the method presented in this work is flexible because the size of the predicted binding site is adjustable. This adaptability is useful when either false positive or negative rates have to be limited.

  4. Activity, exposure rate and spectrum prediction with Java programming

    International Nuclear Information System (INIS)

    In order to envision the radiation exposure during Neutron Activation Analysis (NAA) experiments, a software called Activity Predictor is developed using JavaTM programming language. The Activity Predictor calculates activities, exposure rates and gamma spectra of activated samples for NAA experiments performed at Radiation Science and Engineering Center (RSEC), Penn State Breazeale Reactor (PSBR). The calculation procedure for predictions involves both analytical and Monte Carlo methods. The Activity Predictor software is validated with a series of activation experiments. It has been found that Activity Predictor software calculates the activities and exposure rates precisely. The software also predicts gamma spectrum for each measurement. The predicted spectra agreed partially with measured spectra. The error in net photo peak areas varied from 4.8 to 51.29%, which is considered to be due to simplistic modeling, statistical fluctuations and unknown contaminants in the samples. (author)

  5. Computational predictions suggest that structural similarity in viral polymerases may lead to comparable allosteric binding sites.

    Science.gov (United States)

    Brown, Jodian A; Espiritu, Marie V; Abraham, Joel; Thorpe, Ian F

    2016-08-15

    The identification of ligand-binding sites is often the first step in drug targeting and design. To date there are numerous computational tools available to predict ligand binding sites. These tools can guide or mitigate the need for experimental methods to identify binding sites, which often require significant resources and time. Here, we evaluate four ligand-binding site predictor (LBSP) tools for their ability to predict allosteric sites within the Hepatitis C Virus (HCV) polymerase. Our results show that the LISE LBSP is able to identify all three target allosteric sites within the HCV polymerase as well as a known allosteric site in the Coxsackievirus polymerase. LISE was then employed to identify novel binding sites within the polymerases of the Dengue, West Nile, and Foot-and-mouth Disease viruses. Our results suggest that all three viral polymerases have putative sites that share structural or chemical similarities with allosteric pockets of the HCV polymerase. Thus, these binding locations may represent an evolutionarily conserved structural feature of several viral polymerases that could be exploited for the development of small molecule therapeutics. PMID:27262620

  6. Fluorescence energy transfer studies on the active site of papain

    OpenAIRE

    Henes, Jill B.; Briggs, Martha S.; Sligar, Stephen G.; Fruton, Joseph S.

    1980-01-01

    Measurements have been performed of the excited-state lifetimes and fluorescence yields of papain tryptophan units when acyl derivatives of Phe-glycinal are bound at the active site of the enzyme. The enhancement of tryptophan fluorescence in complexes of papain with the acetyl or benzyloxycarbonyl derivatives is not stereospecific with respect to the configuration of the phenylalanyl residue, and the L and D isomers are equally effective as active-site-directed inhibitors of papain action. E...

  7. Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks.

    Science.gov (United States)

    Pettie, Kade P; Dresch, Jacqueline M; Drewell, Robert A

    2016-08-01

    In the development of the Drosophila embryo, gene expression is directed by the sequence-specific interactions of a large network of protein transcription factors (TFs) and DNA cis-regulatory binding sites. Once the identity of the typically 8-10bp binding sites for any given TF has been determined by one of several experimental procedures, the sequences can be represented in a position weight matrix (PWM) and used to predict the location of additional TF binding sites elsewhere in the genome. Often, alignments of large (>200bp) genomic fragments that have been experimentally determined to bind the TF of interest in Chromatin Immunoprecipitation (ChIP) studies are trimmed under the assumption that the majority of the binding sites are located near the center of all the aligned fragments. In this study, ChIP/chip datasets are analyzed using the corresponding PWMs for the well-studied TFs; CAUDAL, HUNCHBACK, KNIRPS and KRUPPEL, to determine the distribution of predicted binding sites. All four TFs are critical regulators of gene expression along the anterio-posterior axis in early Drosophila development. For all four TFs, the ChIP peaks contain multiple binding sites that are broadly distributed across the genomic region represented by the peak, regardless of the prediction stringency criteria used. This result suggests that ChIP peak trimming may exclude functional binding sites from subsequent analyses.

  8. Predicting mining activity with parallel genetic algorithms

    Science.gov (United States)

    Talaie, S.; Leigh, R.; Louis, S.J.; Raines, G.L.

    2005-01-01

    We explore several different techniques in our quest to improve the overall model performance of a genetic algorithm calibrated probabilistic cellular automata. We use the Kappa statistic to measure correlation between ground truth data and data predicted by the model. Within the genetic algorithm, we introduce a new evaluation function sensitive to spatial correctness and we explore the idea of evolving different rule parameters for different subregions of the land. We reduce the time required to run a simulation from 6 hours to 10 minutes by parallelizing the code and employing a 10-node cluster. Our empirical results suggest that using the spatially sensitive evaluation function does indeed improve the performance of the model and our preliminary results also show that evolving different rule parameters for different regions tends to improve overall model performance. Copyright 2005 ACM.

  9. Key messages from active CO2 storage sites

    Energy Technology Data Exchange (ETDEWEB)

    Wildenborg, T.; Wollenweber, J. [TNO, Princetonlaan 6, 3584 CB Utrecht (Netherlands); Chadwick, A. [BGS, Environmental Science Centre, Keyworth, Nottingham, NG12 5GG (United Kingdom); Deflandre, J.P. [IFP Energies nouvelles, 1-4 avenue de Bois Preau, 92852 Rueil-Malmaison (France); Eiken, O. [Statoil Research Centre, Rotvoll, Arkitekt Ebbells vei 10, 7005 Trondheim (Norway); Mathieson, A. [BP, Alternative Energy, Chertsey Road, Sunbury on Thames (United Kingdom); Metcalfe, R. [QUINTESSA, The Hub, 14 Station Road, Henley-on-Thames, Oxfordshire (United Kingdom); Schmidt Hattenberger, C. [GFZ German Research Centre for Geosciences, Centre for CO2Storage, Potsdam (Germany)

    2013-07-01

    An extensive programme of modelling, monitoring and verification activities was deployed at a set of active storage sites worldwide including Sleipner, In Salah, Ketzin, Weyburn, K12-B and Snoehvit (EU CO2ReMoVe project). All investigated storage sites were well managed and did not have a negative impact on humans or the environment. Time-lapse seismic and pressure monitoring are key in verifying the deep subsurface performance of the storage sites. Evidence gathered during the site characterisation and operational phases is key to handover responsibility of the storage site to governmental authorities after injection has definitely ceased, which is the focus of the follow-up EU project CO2CARE.

  10. Ensemble Prediction and Uncertainty Quantification of the Propagation of Weak Seismic Pulses with Minimal Site Characterization

    Science.gov (United States)

    Vecherin, S.; Ketcham, S.; Parker, M.; Picucci, J.

    2015-12-01

    To make a prediction for the propagation of seismic pulses, one needs to specify physical properties and subsurface ground structure of the site. This information is frequently unknown or estimated with significant uncertainty. We developed a methodology for the ensemble prediction of the propagation of weak seismic pulses for short ranges. The ranges of interest are 10-100 of meters, and the pulse bandwidth is up to 200 Hz. Instead of specifying specific values for viscoelastic site properties, the methodology operates with probability distribution functions of the inputs. This yields ensemble realizations of the pulse at specified locations, where mean, median, and maximum likelihood predictions can be made, and confidence intervals are estimated. Starting with the site's Vs30, the methodology creates an ensemble of plausible vertically stratified Vs profiles for the site. The number and thickness of the layers are modeled using inhomogeneous Poisson process, and the Vs values in the layers are modeled by Gaussian correlated process. The Poisson expectation rate and Vs correlation between adjacent layers take into account layers depth and thickness, and are specific for a site class, as defined by the Federal Emergency Management Agency (FEMA). High-fidelity three-dimension thin layer method (TLM) is used to yield an ensemble of frequency response functions. Comparison with experiments revealed that measured signals are not always within the predicted ensemble. Variance-based global sensitivity analysis has shown that the most significant parameter in the TLM for the prediction of the pulse energy is the shear quality factor, Qs. Some strategies how to account for significant uncertainty in this parameter and to improve accuracy of the ensemble predictions for a specific site are investigated and discussed.

  11. Predicting evolutionary site variability from structure in viral proteins: buriedness, flexibility, and design

    CERN Document Server

    Shahmoradi, Amir; Spielman, Stephanie J; Jackson, Eleisha L; Dawson, Eric T; Meyer, Austin G; Wilke, Claus O

    2014-01-01

    Several recent works have shown that protein structure can predict site-specific evolutionary sequence variation. In particular, sites that are buried and/or have many contacts with other sites in a structure have been shown to evolve more slowly, on average, than surface sites with few contacts. Here, we present a comprehensive study of the extent to which numerous structural properties can predict sequence variation. The structural properties we considered include buriedness (relative solvent accessibility and contact number), structural flexibility (B factors, root-mean-square fluctuations, and variation in dihedral angles), and variability in designed structures. We obtained structural flexibility measures both from molecular dynamics simulations performed on 9 non-homologous viral protein structures and from variation in homologous variants of those proteins, where available. We obtained measures of variability in designed structures from flexible-backbone design in the Rosetta software. We found that mo...

  12. Analysis and prediction of gene splice sites in four Aspergillus genomes

    DEFF Research Database (Denmark)

    Wang, Kai; Ussery, David; Brunak, Søren

    2009-01-01

    , splice site prediction program called NetAspGene, for the genus Aspergillus. Gene sequences from Aspergillus fumigatus, the most common mould pathogen, were used to build and test our model. Compared to many animals and plants, Aspergillus contains smaller introns; thus we have applied a larger window...... better splice site prediction than other available tools. NetAspGene will be very helpful for the study in Aspergillus splice sites and especially in alternative splicing. A webpage for NetAspGene is publicly available at http://www.cbs.dtu.dk/services/NetAspGene....... size on single local networks for training, to cover both donor and acceptor site information. We have applied NetAspGene to other Aspergilli, including Aspergillus nidulans, Aspergillus oryzae, and Aspergillus niger. Evaluation with independent data sets reveal that NetAspGene performs substantially...

  13. GPS-SNO: computational prediction of protein S-nitrosylation sites with a modified GPS algorithm.

    Directory of Open Access Journals (Sweden)

    Yu Xue

    Full Text Available As one of the most important and ubiquitous post-translational modifications (PTMs of proteins, S-nitrosylation plays important roles in a variety of biological processes, including the regulation of cellular dynamics and plasticity. Identification of S-nitrosylated substrates with their exact sites is crucial for understanding the molecular mechanisms of S-nitrosylation. In contrast with labor-intensive and time-consuming experimental approaches, prediction of S-nitrosylation sites using computational methods could provide convenience and increased speed. In this work, we developed a novel software of GPS-SNO 1.0 for the prediction of S-nitrosylation sites. We greatly improved our previously developed algorithm and released the GPS 3.0 algorithm for GPS-SNO. By comparison, the prediction performance of GPS 3.0 algorithm was better than other methods, with an accuracy of 75.80%, a sensitivity of 53.57% and a specificity of 80.14%. As an application of GPS-SNO 1.0, we predicted putative S-nitrosylation sites for hundreds of potentially S-nitrosylated substrates for which the exact S-nitrosylation sites had not been experimentally determined. In this regard, GPS-SNO 1.0 should prove to be a useful tool for experimentalists. The online service and local packages of GPS-SNO were implemented in JAVA and are freely available at: http://sno.biocuckoo.org/.

  14. Predicting the Mutating Distribution at Antigenic Sites of the Influenza Virus

    OpenAIRE

    Hongyang Xu; Yiyan Yang; Shuning Wang; Ruixin Zhu; Tianyi Qiu; Jingxuan Qiu; Qingchen Zhang; Li Jin; Yungang He; Kailin Tang; Zhiwei Cao

    2016-01-01

    Mutations of the influenza virus lead to antigenic changes that cause recurrent epidemics and vaccine resistance. Preventive measures would benefit greatly from the ability to predict the potential distribution of new antigenic sites in future strains. By leveraging the extensive historical records of HA sequences for 90 years, we designed a computational model to simulate the dynamic evolution of antigenic sites in A/H1N1. With templates of antigenic sequences, the model can effectively pred...

  15. Establishing a predictive maintenance (PdM) program at the Hanford Site

    International Nuclear Information System (INIS)

    The production reactors have been shut down for some time. But for the rest of the site, there is currently about 16,000 people engaged in a multi-billion dollar effort to safely process wastes which have been stored at the site since the 1940's. This effort also includes demolition of some older facilities and environmental restoration of much of the site. This is expected to take approximately 30 to 40 years. The concept of a site-wide predictive maintenance (PdM) program began to form in early 1993. Several informal studies showed that the stand alone predictive maintenance groups which had prevailed on site to date were less than 15% effective at trending equipment conditions and predicting failures. To improve the effectiveness of PdM within the company, an engineering analysis by Rick Winslow confirmed that utilization of software networking technology which was now available would significantly overcome many of these built in handicaps. A site-wide predictive maintenance network would make PdM technology accessible to all of the areas and facilities at the site regardless of geographical distances and company division lines. Site resident vibration experts can easily be located and provide consultations on the network. However, it was recognized that strong leadership and management skills would be required within each of the two organizations for effective implementation. To start this process, a letter of understanding and agreement between the facilities and Tank Farm divisions was drafted and endorsed by company management. The agreement assigned the primary responsibility of acquiring the network software and licensee to the Tank Farms division. The acquisition and installation of the network server would be the responsibility of the facilities division. This paper describes the rest of the network development and implementation process

  16. Prediction of Signal Peptide Cleavage Sites with Subsite-Coupled and Template Matching Fusion Algorithm.

    Science.gov (United States)

    Zhang, Shao-Wu; Zhang, Ting-He; Zhang, Jun-Nan; Huang, Yufei

    2014-03-01

    Fast and effective prediction of signal peptides (SP) and their cleavage sites is of great importance in computational biology. The approaches developed to predict signal peptide can be roughly divided into machine learning based, and sliding windows based. In order to further increase the prediction accuracy and coverage of organism for SP cleavage sites, we propose a novel method for predicting SP cleavage sites called Signal-CTF that utilizes machine learning and sliding windows, and is designed for N-termial secretory proteins in a large variety of organisms including human, animal, plant, virus, bacteria, fungi and archaea. Signal-CTF consists of three distinct elements: (1) a subsite-coupled and regularization function with a scaled window of fixed width that selects a set of candidates of possible secretion-cleavable segment for a query secretory protein; (2) a sum fusion system that integrates the outcomes from aligning the cleavage site template sequence with each of the aforementioned candidates in a scaled window of fixed width to determine the best candidate cleavage sites for the query secretory protein; (3) a voting system that identifies the ultimate signal peptide cleavage site among all possible results derived from using scaled windows of different width. When compared with Signal-3L and SignalP 4.0 predictors, the prediction accuracy of Signal-CTF is 4-12 %, 10-25 % higher than that of Signal-3L for human, animal and eukaryote, and SignalP 4.0 for eukaryota, Gram-positive bacteria and Gram-negative bacteria, respectively. Comparing with PRED-SIGNAL and SignalP 4.0 predictors on the 32 archaea secretory proteins of used in Bagos's paper, the prediction accuracy of Signal-CTF is 12.5 %, 25 % higher than that of PRED-SIGNAL and SignalP 4.0, respectively. The predicting results of several long signal peptides show that the Signal-CTF can better predict cleavage sites for long signal peptides than SignalP, Phobius, Philius, SPOCTOPUS, Signal

  17. SITE-94. Discrete-feature modelling of the Aespoe Site: 3. Predictions of hydrogeological parameters for performance assessment

    Energy Technology Data Exchange (ETDEWEB)

    Geier, J.E. [Golder Associates AB, Uppsala (Sweden)

    1996-12-01

    A 3-dimensional, discrete-feature hydrological model is developed. The model integrates structural and hydrologic data for the Aespoe site, on scales ranging from semi regional fracture zones to individual fractures in the vicinity of the nuclear waste canisters. Predicted parameters for the near field include fracture spacing, fracture aperture, and Darcy velocity at each of forty canister deposition holes. Parameters for the far field include discharge location, Darcy velocity, effective longitudinal dispersion coefficient and head gradient, flow porosity, and flow wetted surface, for each canister source that discharges to the biosphere. Results are presented in the form of statistical summaries for a total of 42 calculation cases, which treat a set of 25 model variants in various combinations. The variants for the SITE-94 Reference Case model address conceptual and parametric uncertainty related to the site-scale hydrogeologic model and its properties, the fracture network within the repository, effective semi regional boundary conditions for the model, and the disturbed-rock zone around the repository tunnels and shafts. Two calculation cases simulate hydrologic conditions that are predicted to occur during future glacial episodes. 30 refs.

  18. SITE-94. Discrete-feature modelling of the Aespoe Site: 3. Predictions of hydrogeological parameters for performance assessment

    International Nuclear Information System (INIS)

    A 3-dimensional, discrete-feature hydrological model is developed. The model integrates structural and hydrologic data for the Aespoe site, on scales ranging from semi regional fracture zones to individual fractures in the vicinity of the nuclear waste canisters. Predicted parameters for the near field include fracture spacing, fracture aperture, and Darcy velocity at each of forty canister deposition holes. Parameters for the far field include discharge location, Darcy velocity, effective longitudinal dispersion coefficient and head gradient, flow porosity, and flow wetted surface, for each canister source that discharges to the biosphere. Results are presented in the form of statistical summaries for a total of 42 calculation cases, which treat a set of 25 model variants in various combinations. The variants for the SITE-94 Reference Case model address conceptual and parametric uncertainty related to the site-scale hydrogeologic model and its properties, the fracture network within the repository, effective semi regional boundary conditions for the model, and the disturbed-rock zone around the repository tunnels and shafts. Two calculation cases simulate hydrologic conditions that are predicted to occur during future glacial episodes. 30 refs

  19. Dashboard applications to monitor experiment activities at sites

    Science.gov (United States)

    Andreeva, Julia; Belforte, Stefano; Boehm, Max; Casajus, Adrian; Flix, Josep; Gaidioz, Benjamin; Grigoras, Costin; Kokoszkiewicz, Lukasz; Lanciotti, Elisa; Rocha, Ricardo; Saiz, Pablo; Santinelli, Roberto; Sidorova, Irina; Sciabà, Andrea; Tsaregorodtsev, Andrei

    2010-04-01

    In the framework of a distributed computing environment, such as WLCG, monitoring has a key role in order to keep under control activities going on in sites located in different countries and involving people based in many different sites. To be able to cope with such a large scale heterogeneous infrastructure, it is necessary to have monitoring tools providing a complete and reliable view of the overall performance of the sites. Moreover, the structure of a monitoring system critically depends on the object to monitor and on the users it is addressed to. In this article we will describe two different monitoring systems both aimed to monitor activities and services provided in the WLCG framework, but designed in order to meet the requirements of different users: Site Status Board has an overall view of the services available in all the sites supporting an experiment, whereas Siteview provides a complete view of all the activities going on at a site, for all the experiments supported by the site.

  20. Dashboard applications to monitor experiment activities at sites

    CERN Document Server

    Andreeva, J; Boehm, M; Casajus, A; Flix, J; Gaidioz, B; Grigoras, C; Kokoszkiewicz, L; Lanciotti, E; Rocha, R; Saiz, P; Santinelli, R; Sidorova, I; Sciabà, A; Tsaregorodtsev, A

    2010-01-01

    In the framework of a distributed computing environment, such as WLCG, monitoring has a key role in order to keep under control activities going on in sites located in different countries and involving people based in many different sites. To be able to cope with such a large scale heterogeneous infrastructure, it is necessary to have monitoring tools providing a complete and reliable view of the overall performance of the sites. Moreover, the structure of a monitoring system critically depends on the object to monitor and on the users it is addressed to. In this article we will describe two different monitoring systems both aimed to monitor activities and services provided in the WLCG framework, but designed in order to meet the requirements of different users: Site Status Board has an overall view of the services available in all the sites supporting an experiment, whereas Siteview provides a complete view of all the activities going on at a site, for all the experiments supported by the site.

  1. Dashboard applications to monitor experiment activities at sites

    International Nuclear Information System (INIS)

    In the framework of a distributed computing environment, such as WLCG, monitoring has a key role in order to keep under control activities going on in sites located in different countries and involving people based in many different sites. To be able to cope with such a large scale heterogeneous infrastructure, it is necessary to have monitoring tools providing a complete and reliable view of the overall performance of the sites. Moreover, the structure of a monitoring system critically depends on the object to monitor and on the users it is addressed to. In this article we will describe two different monitoring systems both aimed to monitor activities and services provided in the WLCG framework, but designed in order to meet the requirements of different users: Site Status Board has an overall view of the services available in all the sites supporting an experiment, whereas Siteview provides a complete view of all the activities going on at a site, for all the experiments supported by the site.

  2. Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site.

    Science.gov (United States)

    Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

    2016-04-20

    Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide.

  3. Predicting RNA-binding sites of proteins using support vector machines and evolutionary information

    Directory of Open Access Journals (Sweden)

    Su Emily

    2008-12-01

    Full Text Available Abstract Background RNA-protein interaction plays an essential role in several biological processes, such as protein synthesis, gene expression, posttranscriptional regulation and viral infectivity. Identification of RNA-binding sites in proteins provides valuable insights for biologists. However, experimental determination of RNA-protein interaction remains time-consuming and labor-intensive. Thus, computational approaches for prediction of RNA-binding sites in proteins have become highly desirable. Extensive studies of RNA-binding site prediction have led to the development of several methods. However, they could yield low sensitivities in trade-off for high specificities. Results We propose a method, RNAProB, which incorporates a new smoothed position-specific scoring matrix (PSSM encoding scheme with a support vector machine model to predict RNA-binding sites in proteins. Besides the incorporation of evolutionary information from standard PSSM profiles, the proposed smoothed PSSM encoding scheme also considers the correlation and dependency from the neighboring residues for each amino acid in a protein. Experimental results show that smoothed PSSM encoding significantly enhances the prediction performance, especially for sensitivity. Using five-fold cross-validation, our method performs better than the state-of-the-art systems by 4.90%~6.83%, 0.88%~5.33%, and 0.10~0.23 in terms of overall accuracy, specificity, and Matthew's correlation coefficient, respectively. Most notably, compared to other approaches, RNAProB significantly improves sensitivity by 7.0%~26.9% over the benchmark data sets. To prevent data over fitting, a three-way data split procedure is incorporated to estimate the prediction performance. Moreover, physicochemical properties and amino acid preferences of RNA-binding proteins are examined and analyzed. Conclusion Our results demonstrate that smoothed PSSM encoding scheme significantly enhances the performance of RNA

  4. Gideaa study site. Scope of activities and main results

    International Nuclear Information System (INIS)

    During the period from 1977-1986 SKB (Swedish Nuclear Fuel and Waste Management Co) performed surface and borehole investigations of 14 study sites for the purpose of assessing their suitability for a repository of spent nuclear fuel. The next phase in the SKB site selection programme will be to perform detailed characterization, including characterization from shafts and/or tunnels, of two or three sites. The detailed investigations will continue over several years to provide all the data needed for a licensing application to build a repository. Such an application is foreseen to be given to the authorities around the year 2003. It is presently not clear if anyone of the study sites will be selected as a site for detailed characterization. Other site with geological and/or socio-economical characteristics judged more favourable may very well be the ones selected. However, as a part of the background documentation needed for the site selection studies to come, summary reports will be prepared for most study sites. These reports will include scope of activities, main results, uncertainties and need of complementary investigations. This report concerns the Gideaa study site. (au)

  5. Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes

    Science.gov (United States)

    Zhang, Shaoqiang; Xu, Minli; Su, Zhengchang

    2009-01-01

    Although cis-regulatory binding sites (CRBSs) are at least as important as the coding sequences in a genome, our general understanding of them in most sequenced genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization, which has largely hindered our understanding of many important biological processes. In this article, we describe a novel algorithm for genome-wide de novo prediction of CRBSs with high accuracy. We designed our algorithm to circumvent three identified difficulties for CRBS prediction using comparative genomics principles based on a new method for the selection of reference genomes, a new metric for measuring the similarity of CRBSs, and a new graph clustering procedure. When operon structures are correctly predicted, our algorithm can predict 81% of known individual binding sites belonging to 94% of known cis-regulatory motifs in the Escherichia coli K12 genome, while achieving high prediction specificity. Our algorithm has also achieved similar prediction accuracy in the Bacillus subtilis genome, suggesting that it is very robust, and thus can be applied to any other sequenced prokaryotic genome. When compared with the prior state-of-the-art algorithms, our algorithm outperforms them in both prediction sensitivity and specificity. PMID:19383880

  6. Ensemble approach combining multiple methods improves human transcription start site prediction

    LENUS (Irish Health Repository)

    Dineen, David G

    2010-11-30

    Abstract Background The computational prediction of transcription start sites is an important unsolved problem. Some recent progress has been made, but many promoters, particularly those not associated with CpG islands, are still difficult to locate using current methods. These methods use different features and training sets, along with a variety of machine learning techniques and result in different prediction sets. Results We demonstrate the heterogeneity of current prediction sets, and take advantage of this heterogeneity to construct a two-level classifier (\\'Profisi Ensemble\\') using predictions from 7 programs, along with 2 other data sources. Support vector machines using \\'full\\' and \\'reduced\\' data sets are combined in an either\\/or approach. We achieve a 14% increase in performance over the current state-of-the-art, as benchmarked by a third-party tool. Conclusions Supervised learning methods are a useful way to combine predictions from diverse sources.

  7. Application of GIS in prediction and assessment system of off-site accident consequence for NPP

    International Nuclear Information System (INIS)

    The assessment and prediction software system of off-site accident consequence for Guangdong Nuclear Power Plant (GNARD2.0) is a GIS-based software system. The spatial analysis of radioactive materials and doses with geographic information is available in this system. The structure and functions of the GNARD system and the method of applying ArcView GIS are presented

  8. Proteins and Their Interacting Partners: An Introduction to Protein-Ligand Binding Site Prediction Methods.

    Science.gov (United States)

    Roche, Daniel Barry; Brackenridge, Danielle Allison; McGuffin, Liam James

    2015-12-15

    Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein-ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein-ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein-ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

  9. Improving the prediction of protein binding sites by combining heterogeneous data and Voronoi diagrams

    Directory of Open Access Journals (Sweden)

    Fernandez-Fuentes Narcis

    2011-08-01

    Full Text Available Abstract Background Protein binding site prediction by computational means can yield valuable information that complements and guides experimental approaches to determine the structure of protein complexes. Predictions become even more relevant and timely given the current resolution of protein interaction maps, where there is a very large and still expanding gap between the available information on: (i which proteins interact and (ii how proteins interact. Proteins interact through exposed residues that present differential physicochemical properties, and these can be exploited to identify protein interfaces. Results Here we present VORFFIP, a novel method for protein binding site prediction. The method makes use of broad set of heterogeneous data and defined of residue environment, by means of Voronoi Diagrams that are integrated by a two-steps Random Forest ensemble classifier. Four sets of residue features (structural, energy terms, sequence conservation, and crystallographic B-factors used in different combinations together with three definitions of residue environment (Voronoi Diagrams, sequence sliding window, and Euclidian distance have been analyzed in order to maximize the performance of the method. Conclusions The integration of different forms information such as structural features, energy term, evolutionary conservation and crystallographic B-factors, improves the performance of binding site prediction. Including the information of neighbouring residues also improves the prediction of protein interfaces. Among the different approaches that can be used to define the environment of exposed residues, Voronoi Diagrams provide the most accurate description. Finally, VORFFIP compares favourably to other methods reported in the recent literature.

  10. Proteins and Their Interacting Partners: An Introduction to Protein–Ligand Binding Site Prediction Methods

    Directory of Open Access Journals (Sweden)

    Daniel Barry Roche

    2015-12-01

    Full Text Available Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein–ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein–ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein–ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP and the Continuous Automated Model EvaluatiOn (CAMEO projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

  11. PREDICTION OF SITE RESPONSE SPECTRUM UNDER EARTHQUAKE VIBRATION USING AN OPTIMIZED DEVELOPED ARTIFICIAL NEURAL NETWORK MODEL

    Directory of Open Access Journals (Sweden)

    Reza Esmaeilabadi

    2016-06-01

    Full Text Available Site response spectrum is one of the key factors to determine the maximum acceleration and displacement, as well as structure behavior analysis during earthquake vibrations. The main objective of this paper is to develop an optimized model based on artificial neural network (ANN using five different training algorithms to predict nonlinear site response spectrum subjected to Silakhor earthquake vibrations is. The model output was tested for a specified area in west of Iran. The performance and quality of optimized model under all training algorithms have been examined by various statistical, analytical and graph analyses criteria as well as a comparison with numerical methods. The observed adaptabilities in results indicate a feasible and satisfactory engineering alternative method for predicting the analysis of nonlinear site response.

  12. Snoring Sounds Predict Obstruction Sites and Surgical Response in Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

    Science.gov (United States)

    Lee, Li-Ang; Lo, Yu-Lun; Yu, Jen-Fang; Lee, Gui-She; Ni, Yung-Lun; Chen, Ning-Hung; Fang, Tuan-Jen; Huang, Chung-Guei; Cheng, Wen-Nuan; Li, Hsueh-Yu

    2016-01-01

    Snoring sounds generated by different vibrators of the upper airway may be useful indicators of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study aimed to investigate associations between snoring sounds, obstruction sites, and surgical responses (≥50% reduction in the apnea-hypopnea index [AHI] and Hz; odds ratio [OR], 1.25, 95% confidence interval [CI] 1.05-1.49) and body mass index (OR, 1.48, 95% CI 1.02-2.15) after logistic regression analysis. Tonsil obstruction was significantly, inversely correlated with mean snoring sound intensity (301-850 Hz; OR, 0.84, 95% CI 0.74-0.96). Moreover, baseline tonsil obstruction detected by either DISE or mean snoring sound intensity (301-850 Hz), and AHI could significantly predict the surgical response. Our findings suggest that snoring sound detection may be helpful in determining obstruction sites and predict surgical responses. PMID:27471038

  13. Active chemisorption sites in functionalized ionic liquids for carbon capture.

    Science.gov (United States)

    Cui, Guokai; Wang, Jianji; Zhang, Suojiang

    2016-07-25

    Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined.

  14. Active chemisorption sites in functionalized ionic liquids for carbon capture.

    Science.gov (United States)

    Cui, Guokai; Wang, Jianji; Zhang, Suojiang

    2016-07-25

    Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined. PMID:27243042

  15. Probing the active sites for CO dissociation on ruthenium nanoparticles

    DEFF Research Database (Denmark)

    Strebel, Christian Ejersbo; Murphy, Shane; Nielsen, Rasmus Munksgård;

    2012-01-01

    The active sites for CO dissociation were probed on mass-selected Ru nanoparticles on a HOPG support by temperature programmed desorption spectroscopy using isotopically labelled CO. Combined with transmission electron microscopy we gain insight on how the size and morphology of the nanoparticles...... microscopy. Surprisingly, it was found that larger particles were more active per surface area for CO dissociation. It is suggested that this is due to larger particles exposing a more rough surface than the smaller particles, giving rise to a higher relative amount of under-coordinated adsorption sites...

  16. Prediction of functional sites based on the fuzzy oil drop model.

    Directory of Open Access Journals (Sweden)

    Michał Bryliński

    2007-05-01

    Full Text Available A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. Currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localization of active sites in proteins. This paper describes a computational model that can be used to identify potential areas that are able to interact with other molecules (ligands, substrates, inhibitors, etc.. The model for active site recognition is based on the analysis of hydrophobicity distribution in protein molecules. It is shown, based on the analyses of proteins with known biological activity and of proteins of unknown function, that the region of significantly irregular hydrophobicity distribution in proteins appears to be function related.

  17. Prediction of mutant activity and its application in molecular design of tumor necrosis factor-a

    Institute of Scientific and Technical Information of China (English)

    唐卫东; 奚涛; 王波; 郭冬林; 徐贤秀; 朱德煦

    1997-01-01

    Two models for prediction of the activity and stability of site-directed mutagenesis on tumor necrosis factor-α are established. The models are based on straightforward structural considerations, which do not require the elaboration of site-directed mutagenesis on the protein core and the hydrophobic surface area by analyzing the properties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-α (TNF-α) whose two leucine residues (L29, L157) were mutated. Based on these models, a TNF-α mutant with high activity was created by molecular design.

  18. A kinetic description for sodium and potassium effects on (Na+ plus K+)-adenosine triphosphatase: a model for a two-nonequivalent site potassium activation and an analysis of multiequivalent site models for sodium activation.

    Science.gov (United States)

    Lindenmayer, G E; Schwartz, A; Thompson, H K

    1974-01-01

    1. Dissociation constants for sodium and potassium of a site that modulates the rate of ouabain-(Na(+)+K(+))-ATPase interaction were applied to models for potassium activation of (Na(+)+K(+))-ATPase. The constants for potassium (0.213 mM) and for sodium (13.7 mM) were defined, respectively, as activation constant, K(a) and inhibitory constant, K(i).2. Tests of the one- and the two-equivalent site models, that describe sodium and potassium competition, revealed that neither model adequately predicts the activation effects of potassium in the presence of 100 or 200 mM sodium.3. The potassium-activation data, obtained at low potassium and high sodium, were explained by a two-nonequivalent site model where the dissociation constants of the first site are 0.213 mM for potassium and 13.7 mM for sodium. The second site was characterized by dissociation constants of 0.091 mM for potassium and 74.1 mM for sodium.4. The two-nonequivalent site model adequately predicted the responses to concentrations of potassium between 0.25 and 5 mM in the presence of 100-500 mM sodium. At lower sodium concentrations the predicted responses formed an upper limit for the function of observed activities. This limit was reached at lower concentrations of potassium and higher concentrations of sodium, which inferred saturation of the sodium-activation sites with sodium.5. Sodium-activation data were corrected for sodium interaction with potassium-activation sites by use of the two-nonequivalent site model for potassium activation. Tests of equivalent site models suggested that the corrected data for sodium activation may be most consistent with a model that has three-equivalent sites. Other multiequivalent site models (n = 2, 4, 5 or 6), however, cannot be statistically eliminated as possibilities. The three-equivalent site activation model was characterized by dissociation constants of 1.39 mM for sodium and 11.7 mM for potassium. The system theoretically would be half-maximally activated by

  19. SPE-5 Ground-Motion Prediction at Far-Field Geophone and Accelerometer Array Sites and SPE-5 Moment and Corner-Frequency Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoning [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Patton, Howard John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chen, Ting [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-03-25

    This report offers predictions for the SPE-5 ground-motion and accelerometer array sites. These predictions pertain to the waveform and spectral amplitude at certain geophone sites using Denny&Johnson source model and a source model derived from SPE data; waveform, peak velocity and peak acceleration at accelerometer sites using the SPE source model and the finite-difference simulation with LLNL 3D velocity model; and the SPE-5 moment and corner frequency.

  20. Predicting Physical Activity in Arab American School Children

    Science.gov (United States)

    Martin, Jeffrey J.; McCaughtry, Nate; Shen, Bo

    2008-01-01

    Theoretically grounded research on the determinants of Arab American children's physical activity is virtually nonexistent. Thus, the purpose of our investigation was to evaluate the ability of the theory of planned behavior (TPB) and social cognitive theory (SCT) to predict Arab American children's moderate-to-vigorous physical activity (MVPA).…

  1. Improved Species-Specific Lysine Acetylation Site Prediction Based on a Large Variety of Features Set.

    Science.gov (United States)

    Wuyun, Qiqige; Zheng, Wei; Zhang, Yanping; Ruan, Jishou; Hu, Gang

    2016-01-01

    Lysine acetylation is a major post-translational modification. It plays a vital role in numerous essential biological processes, such as gene expression and metabolism, and is related to some human diseases. To fully understand the regulatory mechanism of acetylation, identification of acetylation sites is first and most important. However, experimental identification of protein acetylation sites is often time consuming and expensive. Therefore, the alternative computational methods are necessary. Here, we developed a novel tool, KA-predictor, to predict species-specific lysine acetylation sites based on support vector machine (SVM) classifier. We incorporated different types of features and employed an efficient feature selection on each type to form the final optimal feature set for model learning. And our predictor was highly competitive for the majority of species when compared with other methods. Feature contribution analysis indicated that HSE features, which were firstly introduced for lysine acetylation prediction, significantly improved the predictive performance. Particularly, we constructed a high-accurate structure dataset of H.sapiens from PDB to analyze the structural properties around lysine acetylation sites. Our datasets and a user-friendly local tool of KA-predictor can be freely available at http://sourceforge.net/p/ka-predictor. PMID:27183223

  2. STarMir Tools for Prediction of microRNA Binding Sites.

    Science.gov (United States)

    Kanoria, Shaveta; Rennie, William; Liu, Chaochun; Carmack, C Steven; Lu, Jun; Ding, Ye

    2016-01-01

    MicroRNAs (miRNAs) are a class of endogenous short noncoding RNAs that regulate gene expression by targeting messenger RNAs (mRNAs), which results in translational repression and/or mRNA degradation. As regulatory molecules, miRNAs are involved in many mammalian biological processes and also in the manifestation of certain human diseases. As miRNAs play central role in the regulation of gene expression, understanding miRNA-binding patterns is essential to gain an insight of miRNA mediated gene regulation and also holds promise for therapeutic applications. Computational prediction of miRNA binding sites on target mRNAs facilitates experimental investigation of miRNA functions. This chapter provides protocols for using the STarMir web server for improved predictions of miRNA binding sites on a target mRNA. As an application module of the Sfold RNA package, the current version of STarMir is an implementation of logistic prediction models developed with high-throughput miRNA binding data from cross-linking immunoprecipitation (CLIP) studies. The models incorporated comprehensive thermodynamic, structural, and sequence features, and were found to make improved predictions of both seed and seedless sites, in comparison to the established algorithms (Liu et al., Nucleic Acids Res 41:e138, 2013). Their broad applicability was indicated by their good performance in cross-species validation. STarMir is freely available at http://sfold.wadsworth.org/starmir.html . PMID:27665594

  3. Activation of phenylalanine hydroxylase by phenylalanine does not require binding in the active site.

    Science.gov (United States)

    Roberts, Kenneth M; Khan, Crystal A; Hinck, Cynthia S; Fitzpatrick, Paul F

    2014-12-16

    Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The k(cat)/K(phe) value is down 10⁴ for the mutant enzyme, and the K(m) value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain.

  4. Active Sites Environmental Monitoring Program: FY 1990 annual report

    Energy Technology Data Exchange (ETDEWEB)

    Wickliff, D.S.; Morrissey, C.M.; Ashwood, T.L.

    1991-10-01

    Chapter 3 of US Department of Energy (DOE) Order 5820.2A (DOE 1988) sets forth requirements for environmental monitoring of active low-level waste (LLW) disposal sites. Active sites are defined as those LLW facilities that were in use on or after the date of the order (September 1988). The transuranic (TRU) waste storage areas in Solid Waste Storage Area (SWSA) 5 North are covered by Chap. 2 of the order. In both chapters, monitoring is required to provide for early warning of leaks before those leaks pose a threat to human health or the environment. Chapter 3 also requires that monitoring be conducted to evaluate the short- and long-term performance of LLW disposal facilities. In accordance with this order, the Solid Waste Operations Department at Oak Ridge National Laboratory (ORNL) has established an Active Sites Environmental Monitoring Program (ASEMP) that is implemented by staff of the Environmental Sciences Division (ESD) at ORNL. This report summarizes data from ASEMP monitoring activities for the final 6 months of FY 1990. A brief summary of the monitoring methodology for each site is presented also.

  5. Active site modeling in copper azurin molecular dynamics simulations

    NARCIS (Netherlands)

    Rizzuti, B; Swart, M; Sportelli, L; Guzzi, R

    2004-01-01

    Active site modeling in molecular dynamics simulations is investigated for the reduced state of copper azurin. Five simulation runs (5 ns each) were performed at room temperature to study the consequences of a mixed electrostatic/constrained modeling for the coordination between the metal and the po

  6. Chemical Modification of Papain and Subtilisin: An Active Site Comparison

    Science.gov (United States)

    St-Vincent, Mireille; Dickman, Michael

    2004-01-01

    An experiment using methyle methanethiosulfonate (MMTS) and phenylmethylsulfonyl flouride (PMSF) to specifically modify the cysteine and serine residues in the active sites of papain and subtilism respectively is demonstrated. The covalent modification of these enzymes and subsequent rescue of papain shows the beginning biochemist that proteins…

  7. The nature of the active site in heterogeneous metal catalysis

    DEFF Research Database (Denmark)

    Nørskov, Jens Kehlet; Bligaard, Thomas; Larsen, Britt Hvolbæk;

    2008-01-01

    This tutorial review, of relevance for the surface science and heterogeneous catalysis communities, provides a molecular-level discussion of the nature of the active sites in metal catalysis. Fundamental concepts such as "Bronsted-Evans-Polanyi relations'' and "volcano curves'' are introduced...

  8. Improving N(6)-methyladenosine site prediction with heuristic selection of nucleotide physical-chemical properties.

    Science.gov (United States)

    Zhang, Ming; Sun, Jia-Wei; Liu, Zi; Ren, Ming-Wu; Shen, Hong-Bin; Yu, Dong-Jun

    2016-09-01

    N(6)-methyladenosine (m(6)A) is one of the most common and abundant post-transcriptional RNA modifications found in viruses and most eukaryotes. m(6)A plays an essential role in many vital biological processes to regulate gene expression. Because of its widespread distribution across the genomes, the identification of m(6)A sites from RNA sequences is of significant importance for better understanding the regulatory mechanism of m(6)A. Although progress has been achieved in m(6)A site prediction, challenges remain. This article aims to further improve the performance of m(6)A site prediction by introducing a new heuristic nucleotide physical-chemical property selection (HPCS) algorithm. The proposed HPCS algorithm can effectively extract an optimized subset of nucleotide physical-chemical properties under the prescribed feature representation for encoding an RNA sequence into a feature vector. We demonstrate the efficacy of the proposed HPCS algorithm under different feature representations, including pseudo dinucleotide composition (PseDNC), auto-covariance (AC), and cross-covariance (CC). Based on the proposed HPCS algorithm, we implemented an m(6)A site predictor, called M6A-HPCS, which is freely available at http://csbio.njust.edu.cn/bioinf/M6A-HPCS. Experimental results over rigorous jackknife tests on benchmark datasets demonstrated that the proposed M6A-HPCS achieves higher success rates and outperforms existing state-of-the-art sequence-based m(6)A site predictors. PMID:27293216

  9. A Python analytical pipeline to identify prohormone precursors and predict prohormone cleavage sites

    Directory of Open Access Journals (Sweden)

    Bruce Southey

    2008-12-01

    Full Text Available Neuropeptides and hormones are signaling molecules that support cell-cell communication in the central nervous system. Experimentally characterizing neuropeptides requires significant efforts because of the complex and variable processing of prohormone precursor proteins into neuropeptides and hormones. We demonstrate the power and flexibility of the Python language to develop components of an bioinformatic analytical pipeline to identify precursors from genomic data and to predict cleavage as these precursors are en route to the final bioactive peptides. We identified 75 precursors in the rhesus genome, predicted cleavage sites using support vector machines and compared the rhesus predictions to putative assignments based on homology to human sequences. The correct classification rate of cleavage using the support vector machines was over 97% for both human and rhesus data sets. The functionality of Python has been important to develop and maintain NeuroPred (http://neuroproteomics.scs.uiuc.edu/neuropred.html, a user-centered web application for the neuroscience community that provides cleavage site prediction from a wide range of models, precision and accuracy statistics, post-translational modifications, and the molecular mass of potential peptides. The combined results illustrate the suitability of the Python language to implement an all-inclusive bioinformatics approach to predict neuropeptides that encompasses a large number of interdependent steps, from scanning genomes for precursor genes to identification of potential bioactive neuropeptides.

  10. A python analytical pipeline to identify prohormone precursors and predict prohormone cleavage sites.

    Science.gov (United States)

    Southey, Bruce R; Sweedler, Jonathan V; Rodriguez-Zas, Sandra L

    2008-01-01

    Neuropeptides and hormones are signaling molecules that support cell-cell communication in the central nervous system. Experimentally characterizing neuropeptides requires significant efforts because of the complex and variable processing of prohormone precursor proteins into neuropeptides and hormones. We demonstrate the power and flexibility of the Python language to develop components of an bioinformatic analytical pipeline to identify precursors from genomic data and to predict cleavage as these precursors are en route to the final bioactive peptides. We identified 75 precursors in the rhesus genome, predicted cleavage sites using support vector machines and compared the rhesus predictions to putative assignments based on homology to human sequences. The correct classification rate of cleavage using the support vector machines was over 97% for both human and rhesus data sets. The functionality of Python has been important to develop and maintain NeuroPred (http://neuroproteomics.scs.uiuc.edu/neuropred.html), a user-centered web application for the neuroscience community that provides cleavage site prediction from a wide range of models, precision and accuracy statistics, post-translational modifications, and the molecular mass of potential peptides. The combined results illustrate the suitability of the Python language to implement an all-inclusive bioinformatics approach to predict neuropeptides that encompasses a large number of interdependent steps, from scanning genomes for precursor genes to identification of potential bioactive neuropeptides.

  11. Nonlinear Predictive Control of Semi-Active Landing Gear System

    OpenAIRE

    Wu, Dongsu; Gu, Hongbin; Liu, Hui

    2010-01-01

    The application of model predictive control and constructive nonlinear control methodology to semi-active landing gear system is studied in this paper. A unified shock absorber mathematical model incorporates solenoid valve’s electromechanical and magnetic dynamics is built to facilitate simulation and controller design. Then we propose a hierarchical control structure to deal with the high nonlinearity. A dual mode model predictive controller as an outer loop controller is developed to gen...

  12. Suction Drain Tip Culture after Spine Surgery: Can It Predict a Surgical Site Infection?

    OpenAIRE

    Ahn, Jae-Sung; Lee, Ho-Jin; Park, Eugene; Park, Il-Young; Lee, Jae Won

    2015-01-01

    Study Design Retrospective clinical study. Purpose To assess the diagnostic value of suction drain tip culture in patients undergoing primary posterior spine surgery. Overview of Literature To date, the diagnostic value of suction drain tip culture for predicting surgical site infection (SSI) has not been firmly established in orthopedic or spinal surgery. Methods In total, 133 patients who underwent primary posterior spine surgery from January 2013 to April 2015 were included in this retrosp...

  13. Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes

    OpenAIRE

    Zhang, Shaoqiang; Xu, Minli; Li, Shan; Su, Zhengchang

    2009-01-01

    Although cis-regulatory binding sites (CRBSs) are at least as important as the coding sequences in a genome, our general understanding of them in most sequenced genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization, which has largely hindered our understanding of many important biological processes. In this article, we describe a novel algorithm for genome-wide de novo prediction of CRBSs with high accuracy. We desi...

  14. Teenagers and social network sites: Do off-line inequalities predict their online social networks?

    OpenAIRE

    Ahn, June

    2011-01-01

    This study analyzes a data set of 701 U.S. teenagers (ages 12-18) that merges an online survey of social network site (SNS) preferences with administrative records from their public school districts. Using a multinomial logistic model, I examine whether offline divides across gender, ethnicity, socioeconomic status, self-esteem, and social capital predict teenagers’ membership into the popular SNSs, Facebook and Myspace. The results show that the characteristics of teens that use Facebook, ...

  15. How well do cognitive and environmental variables predict active commuting?

    Directory of Open Access Journals (Sweden)

    Godin Gaston

    2009-03-01

    Full Text Available Abstract Background In recent years, there has been growing interest in theoretical studies integrating cognitions and environmental variables in the prediction of behaviour related to the obesity epidemic. This is the approach adopted in the present study in reference to the theory of planned behaviour. More precisely, the aim of this study was to determine the contribution of cognitive and environmental variables in the prediction of active commuting to get to and from work or school. Methods A prospective study was carried out with 130 undergraduate and graduate students (93 females; 37 males. Environmental, cognitive and socio-demographic variables were evaluated at baseline by questionnaire. Two weeks later, active commuting (walking/bicycling to get to and from work or school was self-reported by questionnaire. Hierarchical multiple regression analyses were performed to predict intention and behaviour. Results The model predicting behaviour based on cognitive variables explained more variance than the model based on environmental variables (37.4% versus 26.8%; Z = 3.86, p p p Conclusion The results showed that cognitive variables play a more important role than environmental variables in predicting and explaining active commuting. When environmental variables were significant, they were mediated by cognitive variables. Therefore, individual cognitions should remain one of the main focuses of interventions promoting active commuting among undergraduate and graduate students.

  16. Predicting carbon dioxide and energy fluxes across global FLUXNET sites with regression algorithms

    Science.gov (United States)

    Tramontana, Gianluca; Jung, Martin; Schwalm, Christopher R.; Ichii, Kazuhito; Camps-Valls, Gustau; Ráduly, Botond; Reichstein, Markus; Altaf Arain, M.; Cescatti, Alessandro; Kiely, Gerard; Merbold, Lutz; Serrano-Ortiz, Penelope; Sickert, Sven; Wolf, Sebastian; Papale, Dario

    2016-07-01

    Spatio-temporal fields of land-atmosphere fluxes derived from data-driven models can complement simulations by process-based land surface models. While a number of strategies for empirical models with eddy-covariance flux data have been applied, a systematic intercomparison of these methods has been missing so far. In this study, we performed a cross-validation experiment for predicting carbon dioxide, latent heat, sensible heat and net radiation fluxes across different ecosystem types with 11 machine learning (ML) methods from four different classes (kernel methods, neural networks, tree methods, and regression splines). We applied two complementary setups: (1) 8-day average fluxes based on remotely sensed data and (2) daily mean fluxes based on meteorological data and a mean seasonal cycle of remotely sensed variables. The patterns of predictions from different ML and experimental setups were highly consistent. There were systematic differences in performance among the fluxes, with the following ascending order: net ecosystem exchange (R2 0.6), gross primary production (R2> 0.7), latent heat (R2 > 0.7), sensible heat (R2 > 0.7), and net radiation (R2 > 0.8). The ML methods predicted the across-site variability and the mean seasonal cycle of the observed fluxes very well (R2 > 0.7), while the 8-day deviations from the mean seasonal cycle were not well predicted (R2 Fluxes were better predicted at forested and temperate climate sites than at sites in extreme climates or less represented by training data (e.g., the tropics). The evaluated large ensemble of ML-based models will be the basis of new global flux products.

  17. Making DDL Engaging Through Advance Organizers and Prediction Activities

    Institute of Scientific and Technical Information of China (English)

    金忍冬

    2012-01-01

      This paper addresses some of the requirements of the advance organizers and prediction activities for DDL (Data-Driv⁃en Learning) based on multi-modal corpora for learning English as a second language. It analyzes preliminary advantages and dis⁃advantages of using multi-modal corpora for DDL and focuses on key methodological issues related to self-guided learning and corpus operation. Pedagogical suggestions are provided on how to make the multi-modal corpora based DDL engaging in accor⁃dance with Krashen’ s Language Input Hypothesis with the assistance of advance organizers and prediction activities.

  18. A neural network model for olfactory glomerular activity prediction

    Science.gov (United States)

    Soh, Zu; Tsuji, Toshio; Takiguchi, Noboru; Ohtake, Hisao

    2012-12-01

    Recently, the importance of odors and methods for their evaluation have seen increased emphasis, especially in the fragrance and food industries. Although odors can be characterized by their odorant components, their chemical information cannot be directly related to the flavors we perceive. Biological research has revealed that neuronal activity related to glomeruli (which form part of the olfactory system) is closely connected to odor qualities. Here we report on a neural network model of the olfactory system that can predict glomerular activity from odorant molecule structures. We also report on the learning and prediction ability of the proposed model.

  19. On splice site prediction using weight array models: a comparison of smoothing techniques

    Science.gov (United States)

    Taher, Leila; Meinicke, Peter; Morgenstern, Burkhard

    2007-11-01

    In most eukaryotic genes, protein-coding exons are separated by non-coding introns which are removed from the primary transcript by a process called "splicing". The positions where introns are cut and exons are spliced together are called "splice sites". Thus, computational prediction of splice sites is crucial for gene finding in eukaryotes. Weight array models are a powerful probabilistic approach to splice site detection. Parameters for these models are usually derived from m-tuple frequencies in trusted training data and subsequently smoothed to avoid zero probabilities. In this study we compare three different ways of parameter estimation for m-tuple frequencies, namely (a) non-smoothed probability estimation, (b) standard pseudo counts and (c) a Gaussian smoothing procedure that we recently developed.

  20. On splice site prediction using weight array models: a comparison of smoothing techniques

    International Nuclear Information System (INIS)

    In most eukaryotic genes, protein-coding exons are separated by non-coding introns which are removed from the primary transcript by a process called 'splicing'. The positions where introns are cut and exons are spliced together are called 'splice sites'. Thus, computational prediction of splice sites is crucial for gene finding in eukaryotes. Weight array models are a powerful probabilistic approach to splice site detection. Parameters for these models are usually derived from m-tuple frequencies in trusted training data and subsequently smoothed to avoid zero probabilities. In this study we compare three different ways of parameter estimation for m-tuple frequencies, namely (a) non-smoothed probability estimation, (b) standard pseudo counts and (c) a Gaussian smoothing procedure that we recently developed

  1. Prediction and assignment of site occupation and energy levels for Pb2+ ions in crystal hosts

    International Nuclear Information System (INIS)

    The environmental factor he of the host was calculated quantitatively in Pb2+-doped 23 compounds based on the dielectric theory of chemical bond for complex crystals. The relationship between the A band energy EA of Pb2+ and the environmental factor he was intensively studied. The results indicate that EA of Pb2+ decreases linearly with increasing of he. A linear model was proposed which allows us to correctly predict and assign the site occupations and the position of A band for Pb2+-doped compounds if the crystal structure and the refraction index were known. Applied to SrGa2O4:Pb2+, CaAl2B2O7:Pb2+ and SrAl2B2O7:Pb2+, the theoretical predictions are in very good agreement with the experimental data. In SrGa2O4:Pb2+, the excitation spectrum of Pb2+ from two different cation sites was identified: the higher energy band of A (265 nm) from the site of Sr2, and the lower ones (280 nm) from the site of Sr1. - Graphical abstract: The A band energy EA of Pb2+ has linear relationship with environmental factor he.

  2. Position-specific prediction of methylation sites from sequence conservation based on information theory.

    Science.gov (United States)

    Shi, Yinan; Guo, Yanzhi; Hu, Yayun; Li, Menglong

    2015-07-23

    Protein methylation plays vital roles in many biological processes and has been implicated in various human diseases. To fully understand the mechanisms underlying methylation for use in drug design and work in methylation-related diseases, an initial but crucial step is to identify methylation sites. The use of high-throughput bioinformatics methods has become imperative to predict methylation sites. In this study, we developed a novel method that is based only on sequence conservation to predict protein methylation sites. Conservation difference profiles between methylated and non-methylated peptides were constructed by the information entropy (IE) in a wider neighbor interval around the methylation sites that fully incorporated all of the environmental information. Then, the distinctive neighbor residues were identified by the importance scores of information gain (IG). The most representative model was constructed by support vector machine (SVM) for Arginine and Lysine methylation, respectively. This model yielded a promising result on both the benchmark dataset and independent test set. The model was used to screen the entire human proteome, and many unknown substrates were identified. These results indicate that our method can serve as a useful supplement to elucidate the mechanism of protein methylation and facilitate hypothesis-driven experimental design and validation.

  3. Protein function annotation with Structurally Aligned Local Sites of Activity (SALSAs

    Directory of Open Access Journals (Sweden)

    Wang Zhouxi

    2013-02-01

    Full Text Available Abstract Background The prediction of biochemical function from the 3D structure of a protein has proved to be much more difficult than was originally foreseen. A reliable method to test the likelihood of putative annotations and to predict function from structure would add tremendous value to structural genomics data. We report on a new method, Structurally Aligned Local Sites of Activity (SALSA, for the prediction of biochemical function based on a local structural match at the predicted catalytic or binding site. Results Implementation of the SALSA method is described. For the structural genomics protein PY01515 (PDB ID 2aqw from Plasmodium yoelii, it is shown that the putative annotation, Orotidine 5'-monophosphate decarboxylase (OMPDC, is most likely correct. SALSA analysis of YP_001304206.1 (PDB ID 3h3l, a putative sugar hydrolase from Parabacteroides distasonis, shows that its active site does not bear close resemblance to any previously characterized member of its superfamily, the Concanavalin A-like lectins/glucanases. It is noted that three residues in the active site of the thermophilic beta-1,4-xylanase from Nonomuraea flexuosa (PDB ID 1m4w, Y78, E87, and E176, overlap with POOL-predicted residues of similar type, Y168, D153, and E232, in YP_001304206.1. The substrate recognition regions of the two proteins are rather different, suggesting that YP_001304206.1 is a new functional type within the superfamily. A structural genomics protein from Mycobacterium avium (PDB ID 3q1t has been reported to be an enoyl-CoA hydratase (ECH, but SALSA analysis shows a poor match between the predicted residues for the SG protein and those of known ECHs. A better local structural match is obtained with Anabaena beta-diketone hydrolase (ABDH, a known β-diketone hydrolase from Cyanobacterium anabaena (PDB ID 2j5s. This suggests that the reported ECH function of the SG protein is incorrect and that it is more likely a β-diketone hydrolase. Conclusions

  4. Complementing computationally predicted regulatory sites in Tractor_DB using a pattern matching approach.

    Science.gov (United States)

    Guía, Marylens Hernández; Pérez, Abel González; Angarica, Vladimir Espinosa; Vasconcelos, Ana T; Collado-Vides, Julio

    2005-01-01

    Prokaryotic genomes annotation has focused on genes location and function. The lack of regulatory information has limited the knowledge on cellular transcriptional regulatory networks. However, as more phylogenetically close genomes are sequenced and annotated, the implementation of phylogenetic footprinting strategies for the recognition of regulators and their regulons becomes more important. In this paper we describe a comparative genomics approach to the prediction of new gamma-proteobacterial regulon members. We take advantage of the phylogenetic proximity of Escherichia coli and other 16 organisms of this subdivision and the intensive search of the space sequence provided by a pattern-matching strategy. Using this approach we complement predictions of regulatory sites made using statistical models currently stored in Tractor_DB, and increase the number of transcriptional regulators with predicted binding sites up to 86. All these computational predictions may be reached at Tractor_DB (www.bioinfo.cu/Tractor_DB, www.tractor.lncc.br, www.ccg.unam.mx/Computational_Genomics/tractorDB/). We also take a first step in this paper towards the assessment of the conservation of the architecture of the regulatory network in the gamma-proteobacteria through evaluating the conservation of the overall connectivity of the network. PMID:15972018

  5. High DNA melting temperature predicts transcription start site location in human and mouse.

    LENUS (Irish Health Repository)

    Dineen, David G

    2009-12-01

    The accurate computational prediction of transcription start sites (TSS) in vertebrate genomes is a difficult problem. The physicochemical properties of DNA can be computed in various ways and a many combinations of DNA features have been tested in the past for use as predictors of transcription. We looked in detail at melting temperature, which measures the temperature, at which two strands of DNA separate, considering the cooperative nature of this process. We find that peaks in melting temperature correspond closely to experimentally determined transcription start sites in human and mouse chromosomes. Using melting temperature alone, and with simple thresholding, we can predict TSS with accuracy that is competitive with the most accurate state-of-the-art TSS prediction methods. Accuracy is measured using both experimentally and manually determined TSS. The method works especially well with CpG island containing promoters, but also works when CpG islands are absent. This result is clear evidence of the important role of the physical properties of DNA in the process of transcription. It also points to the importance for TSS prediction methods to include melting temperature as prior information.

  6. NBA-Palm: prediction of palmitoylation site implemented in Naïve Bayes algorithm

    Directory of Open Access Journals (Sweden)

    Jin Changjiang

    2006-10-01

    Full Text Available Abstract Background Protein palmitoylation, an essential and reversible post-translational modification (PTM, has been implicated in cellular dynamics and plasticity. Although numerous experimental studies have been performed to explore the molecular mechanisms underlying palmitoylation processes, the intrinsic feature of substrate specificity has remained elusive. Thus, computational approaches for palmitoylation prediction are much desirable for further experimental design. Results In this work, we present NBA-Palm, a novel computational method based on Naïve Bayes algorithm for prediction of palmitoylation site. The training data is curated from scientific literature (PubMed and includes 245 palmitoylated sites from 105 distinct proteins after redundancy elimination. The proper window length for a potential palmitoylated peptide is optimized as six. To evaluate the prediction performance of NBA-Palm, 3-fold cross-validation, 8-fold cross-validation and Jack-Knife validation have been carried out. Prediction accuracies reach 85.79% for 3-fold cross-validation, 86.72% for 8-fold cross-validation and 86.74% for Jack-Knife validation. Two more algorithms, RBF network and support vector machine (SVM, also have been employed and compared with NBA-Palm. Conclusion Taken together, our analyses demonstrate that NBA-Palm is a useful computational program that provides insights for further experimentation. The accuracy of NBA-Palm is comparable with our previously described tool CSS-Palm. The NBA-Palm is freely accessible from: http://www.bioinfo.tsinghua.edu.cn/NBA-Palm.

  7. Mapping the active site of vaccinia virus RNA triphosphatase

    International Nuclear Information System (INIS)

    The RNA triphosphatase component of vaccinia virus mRNA capping enzyme (the product of the viral D1 gene) belongs to a family of metal-dependent phosphohydrolases that includes the RNA triphosphatases of fungi, protozoa, Chlorella virus, and baculoviruses. The family is defined by two glutamate-containing motifs (A and C) that form the metal-binding site. Most of the family members resemble the fungal and Chlorella virus enzymes, which have a complex active site located within the hydrophilic interior of a topologically closed eight-stranded β barrel (the so-called ''triphosphate tunnel''). Here we queried whether vaccinia virus capping enzyme is a member of the tunnel subfamily, via mutational mapping of amino acids required for vaccinia triphosphatase activity. We identified four new essential side chains in vaccinia D1 via alanine scanning and illuminated structure-activity relationships by conservative substitutions. Our results, together with previous mutational data, highlight a constellation of six acidic and three basic amino acids that likely compose the vaccinia triphosphatase active site (Glu37, Glu39, Arg77, Lys107, Glu126, Asp159, Lys161, Glu192, and Glu194). These nine essential residues are conserved in all vertebrate and invertebrate poxvirus RNA capping enzymes. We discerned no pattern of clustering of the catalytic residues of the poxvirus triphosphatase that would suggest structural similarity to the tunnel proteins (exclusive of motifs A and C). We infer that the poxvirus triphosphatases are a distinct lineage within the metal-dependent RNA triphosphatase family. Their unique active site, which is completely different from that of the host cell's capping enzyme, recommends the poxvirus RNA triphosphatase as a molecular target for antipoxviral drug discovery

  8. Stock Price Change Rate Prediction by Utilizing Social Network Activities

    Directory of Open Access Journals (Sweden)

    Shangkun Deng

    2014-01-01

    Full Text Available Predicting stock price change rates for providing valuable information to investors is a challenging task. Individual participants may express their opinions in social network service (SNS before or after their transactions in the market; we hypothesize that stock price change rate is better predicted by a function of social network service activities and technical indicators than by a function of just stock market activities. The hypothesis is tested by accuracy of predictions as well as performance of simulated trading because success or failure of prediction is better measured by profits or losses the investors gain or suffer. In this paper, we propose a hybrid model that combines multiple kernel learning (MKL and genetic algorithm (GA. MKL is adopted to optimize the stock price change rate prediction models that are expressed in a multiple kernel linear function of different types of features extracted from different sources. GA is used to optimize the trading rules used in the simulated trading by fusing the return predictions and values of three well-known overbought and oversold technical indicators. Accumulated return and Sharpe ratio were used to test the goodness of performance of the simulated trading. Experimental results show that our proposed model performed better than other models including ones using state of the art techniques.

  9. Predicting the macroseismic intensity from early radiated P wave energy for on-site earthquake early warning in Italy

    Science.gov (United States)

    Brondi, P.; Picozzi, M.; Emolo, A.; Zollo, A.; Mucciarelli, M.

    2015-10-01

    Earthquake Early Warning Systems (EEWS) are potentially effective tools for risk mitigation in active seismic regions. The present study explores the possibility of predicting the macroseismic intensity within EEW timeframes using the squared velocity integral (IV2) measured on the early P wave signals, a proxy for the P wave radiated energy of earthquakes. This study shows that IV2 correlates better than the peak displacement measured on P waves with both the peak ground velocity and the Housner Intensity, with the latter being recognized by engineers as a reliable proxy for damage assessment. Therefore, using the strong motion recordings of the Italian Accelerometric Archive, a novel relationship between the parameter IV2 and the macroseismic intensity (IM) has been derived. The validity of this relationship has been assessed using the strong motion recordings of the Istituto Nazionale di Geofisica e Vulcanologia Strong Motion Data and Osservatorio Sismico delle Strutture databases, as well as, in the case of the MW 6, 29 May 2012 Emilia earthquake (Italy), comparing the predicted intensities with the ones observed after a macroseismic survey. Our results indicate that P wave IV2 can become a key parameter for the design of on-site EEWS, capable of proving real-time predictions of the IM at target sites.

  10. Using Tree-Ring Width Data From 1000 Sites to Predict how American Forests Will Respond to Climate Change

    Science.gov (United States)

    Williams, P.; Still, C. J.; Leavitt, S. W.; Fischer, D. T.

    2007-12-01

    Beginning in the early 1900s, tree-ring scientists began analyzing the relative widths of annual growth rings preserved in the cross-sections of trees. Over the years, many ring-width index chronologies, each representing a specific site and species, have been developed and analyzed to infer details regarding past climate, growth response to environmental fluctuation, fire activity, logging practices by past societies, and more. Of the many ring-width chronologies constructed, 1035 represent sites within the continental United States and have been published online within The International Tree-Ring Data Bank as of September 2007 (ITRDB, http://www.ncdc.noaa.gov/paleo/treering.html). Approximately 85% of these sites are located west of the Mississippi River. Here we present results from a three-step study, using this large reserve of tree-growth data to determine how various tree species in various regions have responded to climate fluctuations in the past and how they can be expected to respond to future change. In the first step, we used linear regression to compare each time series of ring-width index values to a suite of local monthly climate variables that may influence tree growth, such as rainfall, temperature, and drought severity (PDSI). We identified the range of months (of a 24- month period) during which each climate parameter most strongly affects growth by comparing Pearson correlation coefficients. In the second step, we identified all sites where at least one climate parameter, during some rage of months, correlates significantly (95% confidence) with ring-width index values. For each of these sites, we constructed a growth model that uses each significantly correlating climate parameter as a growth predictor. In the third step, we applied the growth model to predict the next 100 years of growth response to a monthly climate forecast created by the Hadley Centre for Climate Prediction and Research. This forecast (HadCM3 IS92a) assumes a business as

  11. Decommissioning and decontamination activity, Gnome Site, Eddy County, New Mexico

    International Nuclear Information System (INIS)

    The purpose of this assessment is to present a brief description of the proposed activity and its potential impacts on the environment. This assessment will constitute an evaluation as to whether or not a formal Environmental Statement need be prepared. As background to the proposed activity, Project Gnome was an underground nuclear test conducted in December 1961 as part of the PLOWSHARE Program. The project site is located about 25 miles southeast of Carlsbad, New Mexico. By means of an excavated shaft and tunnel, a 3-kiloton nuclear explosive was emplaced and detonated in a salt bed about 1200 feet below the surface. The uncontaminated rock and salt muck from the original excavation and subsequent contaminated muck and minor construction debris from reentry activities into the nuclear cavity is commingled and stored in a pile near the Gnome/Coach Shaft. Other areas on the site are known to have been contaminated. In 1969, a program was conducted to cleanup and dispose of all surface contamination to whatever depth it occurred in excess of 0.1 mR/hr. Contaminated materials and soil were collected and disposed into the Gnome shaft, which was filled and sealed. Since then, NV has proposed to DOE/HQ much lower criteria for residual radioactive contamination for the Gnome Site. These proposed criteria were to collect and dispose of surficial materials which contain more than 2 x 10-5 microcuries per gram of soil for beta/gamma emitters and 3 x 10-2 microcuries per milliliter of tritium in soil moisture. According to the latest reconnaissance in 1972, low concentrations of Cs-137, Sr-90 and tritium were present at various locations on the site in excess of these proposed guidelines. Other operational areas within the site are suspected of containing radioactive contamination in much lesser volume, which are to be determined by careful probing and monitoring, as described in the next section

  12. Active serine involved in the stabilization of the active site loop in the Humicola lanuginosa lipase

    DEFF Research Database (Denmark)

    Peters, Günther H.j.; Svendsen, A.; Langberg, H.;

    1998-01-01

    reveal that the hinges of the active site lid are more flexible in the wild-type Hll than in S146A. In contrast, larger fluctuations are observed in the middle region of the active site loop in S 146A than in Hll. These findings reveal that the single mutation (S146A) of the active site serine leads......We have investigated the binding properties of and dynamics in Humicola lanuginosa lipase (HII) and the inactive mutant S146A (active Ser146 substituted with Ala) using fluorescence spectroscopy and molecular dynamics simulations, respectively. Hll and S146A show significantly different binding......, whereas only small changes are observed for I-Ill suggesting that the active site Lid in the latter opens more easily and hence more lipase molecules are bound to the liposomes. These observations are in agreement with molecular dynamics simulations and subsequent essential dynamics analyses. The results...

  13. Combining features in a graphical model to predict protein binding sites.

    Science.gov (United States)

    Wierschin, Torsten; Wang, Keyu; Welter, Marlon; Waack, Stephan; Stanke, Mario

    2015-05-01

    Large efforts have been made in classifying residues as binding sites in proteins using machine learning methods. The prediction task can be translated into the computational challenge of assigning each residue the label binding site or non-binding site. Observational data comes from various possibly highly correlated sources. It includes the structure of the protein but not the structure of the complex. The model class of conditional random fields (CRFs) has previously successfully been used for protein binding site prediction. Here, a new CRF-approach is presented that models the dependencies of residues using a general graphical structure defined as a neighborhood graph and thus our model makes fewer independence assumptions on the labels than sequential labeling approaches. A novel node feature "change in free energy" is introduced into the model, which is then denoted by ΔF-CRF. Parameters are trained with an online large-margin algorithm. Using the standard feature class relative accessible surface area alone, the general graph-structure CRF already achieves higher prediction accuracy than the linear chain CRF of Li et al. ΔF-CRF performs significantly better on a large range of false positive rates than the support-vector-machine-based program PresCont of Zellner et al. on a homodimer set containing 128 chains. ΔF-CRF has a broader scope than PresCont since it is not constrained to protein subgroups and requires no multiple sequence alignment. The improvement is attributed to the advantageous combination of the novel node feature with the standard feature and to the adopted parameter training method.

  14. The purification of affinity-labelled active-site peptides

    International Nuclear Information System (INIS)

    The isolation of the labelled peptide from the protein digest, following the affinity labelling of the active sites of enzymes or antibodies, is described. Single-step affinity chromatography utilises the affinity of the native enzymes or antibody for the ligand used to label the same protein. The labelled peptide is the only one in the digest that displays affinity for the immobilised protein and can be released with eluants that dissociate the protein-ligand complex. (Auth.)

  15. Active sites in char gasification: Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, M.; Lilly, W.D.; Perkins, M.T.; Hradil, G.; Calo, J.M.; Suuberg, E.M.

    1987-09-01

    Among the key variables in the design of gasifiers and combustors is the reactivity of the chars which must be gasified or combusted. Significant loss of unburned char is unacceptable in virtually any process; the provision of sufficient residence time for complete conversion is essential. A very wide range of reactivities are observed, depending upon the nature of the char in a process. The current work focuses on furthering the understanding of gasification reactivities of chars. It has been well established that the reactivity of char to gasification generally depends upon three principal factors: (1) the concentration of ''active sites'' in the char; (2) mass transfer within the char; and (3) the type and concentration of catalytic impurities in the char. The present study primarily addresses the first factor. The subject of this research is the origin, nature, and fate of active sites in chars derived from parent hydrocarbons with coal-like structure. The nature and number of the active sites and their reactivity towards oxygen are examined in ''model'' chars derived from phenol-formaldehyde type resins. How the active sites are lost by the process of thermal annealing during heat treatment of chars are studied, and actual rate for the annealing process is derived. Since intrinsic char reactivities are of primary interest in the present study, a fair amount of attention was given to the model char synthesis and handling so that the effect of catalytic impurities and oxygen-containing functional groups in the chemical structure of the material were minimized, if not completely eliminated. The project would not be considered complete without comparing characteristic features of synthetic chars with kinetic behavior exhibited by natural chars, including coal chars.

  16. Exploiting Innocuous Activity for Correlating Users Across Sites

    OpenAIRE

    Goga, Oana; Lei, Howard; Parthasarathi, Sree Hari Krishnan; Friedland, Gerald; Sommer, Robin; Teixeira, Renata

    2013-01-01

    International audience We study how potential attackers can identify accounts on different social network sites that all belong to the same user, exploiting only innocuous activity that inherently comes with posted content. We examine three specific features on Yelp, Flickr, and Twitter: the geo-location attached to a user's posts, the timestamp of posts, and the user's writing style as captured by language models. We show that among these three features the location of posts is the most po...

  17. Inhibition and active-site modelling of prolidase.

    Science.gov (United States)

    King, G F; Crossley, M J; Kuchel, P W

    1989-03-15

    Consideration of the active-site model of prolidase led us to examine azetidine, pyrrolidine and piperidine substrate analogs as potential in vivo inhibitors of the enzyme. One of these, N-benzyloxycarbonyl-L-proline, was shown to be a potent competitive inhibitor of porcine kidney prolidase (Ki = 90 microM); its rapid protein-mediated permeation of human and sheep erythrocytes suggests that it may be effective in vivo. The higher homolog, N-benzyloxycarbonyl-L-pipecolic acid, was also a potent inhibitor of the enzyme while the antihypertensive drugs, captopril and enalaprilat, were shown to have mild and no inhibitory effects, respectively. Analysis of inhibitor action and consideration of X-ray crystallographic data of relevant Mn2+ complexes allowed the active-site model of prolidase to be further refined; a new model is presented in which the substrate acts as a bidentate ligand towards the active-site manganous ion. Various aspects of the new model help to explain why Mn2+ has been 'chosen' by the enzyme in preference to other biologically available metal ions. PMID:2924773

  18. Rapid and accurate prediction and scoring of water molecules in protein binding sites.

    Directory of Open Access Journals (Sweden)

    Gregory A Ross

    Full Text Available Water plays a critical role in ligand-protein interactions. However, it is still challenging to predict accurately not only where water molecules prefer to bind, but also which of those water molecules might be displaceable. The latter is often seen as a route to optimizing affinity of potential drug candidates. Using a protocol we call WaterDock, we show that the freely available AutoDock Vina tool can be used to predict accurately the binding sites of water molecules. WaterDock was validated using data from X-ray crystallography, neutron diffraction and molecular dynamics simulations and correctly predicted 97% of the water molecules in the test set. In addition, we combined data-mining, heuristic and machine learning techniques to develop probabilistic water molecule classifiers. When applied to WaterDock predictions in the Astex Diverse Set of protein ligand complexes, we could identify whether a water molecule was conserved or displaced to an accuracy of 75%. A second model predicted whether water molecules were displaced by polar groups or by non-polar groups to an accuracy of 80%. These results should prove useful for anyone wishing to undertake rational design of new compounds where the displacement of water molecules is being considered as a route to improved affinity.

  19. Prediction of functional sites based on the fuzzy oil drop model.

    OpenAIRE

    Michał Bryliński; Katarzyna Prymula; Wiktor Jurkowski; Marek Kochańczyk; Ewa Stawowczyk; Leszek Konieczny; Irena Roterman

    2007-01-01

    A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. Currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localiza...

  20. Prediction of Functional Sites Based on the Fuzzy Oil Drop Model

    OpenAIRE

    Bryliński, Michał; Prymula, Katarzyna; Jurkowski, Wiktor; Kochańczyk, Marek; Stawowczyk, Ewa; Konieczny, Leszek; Roterman, Irena

    2007-01-01

    A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. Currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localiza...

  1. SABER: a computational method for identifying active sites for new reactions.

    Science.gov (United States)

    Nosrati, Geoffrey R; Houk, K N

    2012-05-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified.

  2. Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy

    Science.gov (United States)

    Dierksen, Gregory; Betensky, Rebecca; Gidicsin, Christopher; Halpin, Amy; Becker, Alex; Carmasin, Jeremy; Ayres, Alison; Schwab, Kristin; Viswanathan, Anand; Salat, David; Rosand, Jonathan; Johnson, Keith A.; Greenberg, Steven M.

    2012-01-01

    Objective: We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA). Methods: We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at “simulated” hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained. Results: Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1–9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23–1.46) than simulated lesions (1.14, 95% CI 1.07–1.22, p < 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p < 0.0001). Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p = 0.003). Conclusions: Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA. PMID:22786597

  3. Short communication: genetic variability in the predicted microRNA target sites of caprine casein genes.

    Science.gov (United States)

    Zidi, A; Amills, M; Tomás, A; Vidal, O; Ramírez, O; Carrizosa, J; Urrutia, B; Serradilla, J M; Clop, A

    2010-04-01

    The main goal of the current work was to identify single nucleotide polymorphisms (SNP) that might create or disrupt microRNA (miRNA) target sites in the caprine casein genes. The 3' untranslated regions of the goat alpha(S1)-, alpha(S2)-, beta-, and kappa-casein genes (CSN1S1, CSN1S2, CSN2, and CSN3, respectively) were resequenced in 25 individuals of the Murciano-Granadina, Cashmere, Canarian, Saanen, and Sahelian breeds. Five SNP were identified through this strategy: c.175C>T at CSN1S1; c.109T>C, c.139G>C, and c.160T>C at CSN1S2; and c.216C>T at CSN2. Analysis with the Patrocles Finder tool predicted that all of these SNP are located within regions complementary to the seed of diverse miRNA sequences. These in silico results suggest that polymorphism at miRNA target sites might have some effect on casein expression. We explored this issue by genotyping the c.175C>T SNP (CSN1S1) in 85 Murciano-Granadina goats with records for milk CSN1S1 concentrations. This substitution destroys a putative target site for miR-101, a miRNA known to be expressed in the bovine mammary gland. Although TT goats had higher levels (6.25 g/L) of CSN1S1 than their CT (6.05 g/L) and CC (6.04 g/L) counterparts, these differences were not significant. Experimental confirmation of the miRNA target sites predicted in the current work and performance of additional association analyses in other goat populations will be an essential step to find out if polymorphic miRNA target sites constitute an important source of variation in casein expression.

  4. Seismic activity parameters of the Finnish potential repository sites

    Energy Technology Data Exchange (ETDEWEB)

    Saari, J. [Fortum Engineering Oy, Vantaa (Finland)

    2000-10-01

    Posiva Oy has started a project for estimating the possible earthquake induced rock movements on the deposition holes containing canisters of spent nuclear fuel. These estimates will be made for the four investigation sites, Romuvaara, Kivetty, Olkiluoto and Haestholmen. This study deals with the current and future seismicity associated with the above mentioned sites. Seismic belts that participate the seismic behaviour of the studied sites have been identified and the magnitude-frequency distributions of these belts have been estimated. The seismic activity parameters of the sites have been deduced from the characteristics of the seismic belts in order to forecast the seismicity during the next 100,000 years. The report discusses the possible earthquakes induced by future glaciation. The seismic interpretation seems to indicate that the previous postglacial faults in Finnish Lapland have been generated in compressional environment. The orientation of the rather uniform compression has been NW-SE, which coincide with the current stress field. It seems that, although the impact of postglacial crustal rebound must have been significant, the impact of plate tectonics has been dominant. A major assumption of this study has been that future seismicity will generally resemble the current seismicity. However, when the postglacial seismicity is concerned, the magnitude-frequency distribution is likely different and the expected maximum magnitude will be higher. Maximum magnitudes of future postglacial earthquakes have been approximated by strain release examinations. Seismicity has been examined within the framework of the lineament maps, in order to associate the future significant earthquakes with active fault zones in the vicinity of the potential repository sites. (orig.)

  5. Evaluation of WEPP for runoff and sediment yield prediction on natural gas well sites

    Science.gov (United States)

    Natural gas exploration and production, with nearly 30,000 new wells drilled each year in the US, requires land disturbing activities that can accelerate soil loss. Erosion modeling has been successfully used for decades to predict soil loss and conservation effects on agricultural fields, rangelan...

  6. Impediments to predicting site response: Seismic property estimation and modeling simplifications

    Science.gov (United States)

    Thompson, E.M.; Baise, L.G.; Kayen, R.E.; Guzina, B.B.

    2009-01-01

    We compare estimates of the empirical transfer function (ETF) to the plane SH-wave theoretical transfer function (TTF) within a laterally constant medium for invasive and noninvasive estimates of the seismic shear-wave slownesses at 13 Kiban-Kyoshin network stations throughout Japan. The difference between the ETF and either of the TTFs is substantially larger than the difference between the two TTFs computed from different estimates of the seismic properties. We show that the plane SH-wave TTF through a laterally homogeneous medium at vertical incidence inadequately models observed amplifications at most sites for both slowness estimates, obtained via downhole measurements and the spectral analysis of surface waves. Strategies to improve the predictions can be separated into two broad categories: improving the measurement of soil properties and improving the theory that maps the 1D soil profile onto spectral amplification. Using an example site where the 1D plane SH-wave formulation poorly predicts the ETF, we find a more satisfactory fit to the ETF by modeling the full wavefield and incorporating spatially correlated variability of the seismic properties. We conclude that our ability to model the observed site response transfer function is limited largely by the assumptions of the theoretical formulation rather than the uncertainty of the soil property estimates.

  7. A homology-based pipeline for global prediction of post-translational modification sites

    Science.gov (United States)

    Chen, Xiang; Shi, Shao-Ping; Xu, Hao-Dong; Suo, Sheng-Bao; Qiu, Jian-Ding

    2016-05-01

    The pathways of protein post-translational modifications (PTMs) have been shown to play particularly important roles for almost any biological process. Identification of PTM substrates along with information on the exact sites is fundamental for fully understanding or controlling biological processes. Alternative computational strategies would help to annotate PTMs in a high-throughput manner. Traditional algorithms are suited for identifying the common organisms and tissues that have a complete PTM atlas or extensive experimental data. While annotation of rare PTMs in most organisms is a clear challenge. In this work, to this end we have developed a novel homology-based pipeline named PTMProber that allows identification of potential modification sites for most of the proteomes lacking PTMs data. Cross-promotion E-value (CPE) as stringent benchmark has been used in our pipeline to evaluate homology to known modification sites. Independent-validation tests show that PTMProber achieves over 58.8% recall with high precision by CPE benchmark. Comparisons with other machine-learning tools show that PTMProber pipeline performs better on general predictions. In addition, we developed a web-based tool to integrate this pipeline at http://bioinfo.ncu.edu.cn/PTMProber/index.aspx. In addition to pre-constructed prediction models of PTM, the website provides an extensional functionality to allow users to customize models.

  8. The Prediction of Calpain Cleavage Sites with the mRMR and IFS Approaches

    Directory of Open Access Journals (Sweden)

    Wenyi Zhang

    2013-01-01

    Full Text Available Calpains are an important family of the Ca2+-dependent cysteine proteases which catalyze the limited proteolysis of many specific substrates. Calpains play crucial roles in basic physiological and pathological processes, and identification of the calpain cleavage sites may facilitate the understanding of the molecular mechanisms and biological function. But traditional experiment approaches to predict the sites are accurate, and are always labor-intensive and time-consuming. Thus, it is common to see that computational methods receive increasing attention due to their convenience and fast speed in recent years. In this study, we develop a new predictor based on the support vector machine (SVM with the maximum relevance minimum redundancy (mRMR method followed by incremental feature selection (IFS. And we concern the feature of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure, and solvent accessibility to represent the calpain cleavage sites. Experimental results show that the performance of our predictor is better than several other state-of- the-art predictors, whose average prediction accuracy is 79.49%, sensitivity is 62.31%, and specificity is 88.12%. Since user-friendly and publicly accessible web servers represent the future direction for developing practically more useful predictors, here we have provided a web-server for the method presented in this paper.

  9. A homology-based pipeline for global prediction of post-translational modification sites.

    Science.gov (United States)

    Chen, Xiang; Shi, Shao-Ping; Xu, Hao-Dong; Suo, Sheng-Bao; Qiu, Jian-Ding

    2016-01-01

    The pathways of protein post-translational modifications (PTMs) have been shown to play particularly important roles for almost any biological process. Identification of PTM substrates along with information on the exact sites is fundamental for fully understanding or controlling biological processes. Alternative computational strategies would help to annotate PTMs in a high-throughput manner. Traditional algorithms are suited for identifying the common organisms and tissues that have a complete PTM atlas or extensive experimental data. While annotation of rare PTMs in most organisms is a clear challenge. In this work, to this end we have developed a novel homology-based pipeline named PTMProber that allows identification of potential modification sites for most of the proteomes lacking PTMs data. Cross-promotion E-value (CPE) as stringent benchmark has been used in our pipeline to evaluate homology to known modification sites. Independent-validation tests show that PTMProber achieves over 58.8% recall with high precision by CPE benchmark. Comparisons with other machine-learning tools show that PTMProber pipeline performs better on general predictions. In addition, we developed a web-based tool to integrate this pipeline at http://bioinfo.ncu.edu.cn/PTMProber/index.aspx. In addition to pre-constructed prediction models of PTM, the website provides an extensional functionality to allow users to customize models.

  10. SUMOhydro: a novel method for the prediction of sumoylation sites based on hydrophobic properties.

    Science.gov (United States)

    Chen, Yong-Zi; Chen, Zhen; Gong, Yu-Ai; Ying, Guoguang

    2012-01-01

    Sumoylation is one of the most essential mechanisms of reversible protein post-translational modifications and is a crucial biochemical process in the regulation of a variety of important biological functions. Sumoylation is also closely involved in various human diseases. The accurate computational identification of sumoylation sites in protein sequences aids in experimental design and mechanistic research in cellular biology. In this study, we introduced amino acid hydrophobicity as a parameter into a traditional binary encoding scheme and developed a novel sumoylation site prediction tool termed SUMOhydro. With the assistance of a support vector machine, the proposed method was trained and tested using a stringent non-redundant sumoylation dataset. In a leave-one-out cross-validation, the proposed method yielded an excellent performance with a correlation coefficient, specificity, sensitivity and accuracy equal to 0.690, 98.6%, 71.1% and 97.5%, respectively. In addition, SUMOhydro has been benchmarked against previously described predictors based on an independent dataset, thereby suggesting that the introduction of hydrophobicity as an additional parameter could assist in the prediction of sumoylation sites. Currently, SUMOhydro is freely accessible at http://protein.cau.edu.cn/others/SUMOhydro/. PMID:22720073

  11. LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation

    Directory of Open Access Journals (Sweden)

    Schroeder Michael

    2006-09-01

    Full Text Available Abstract Background Identifying pockets on protein surfaces is of great importance for many structure-based drug design applications and protein-ligand docking algorithms. Over the last ten years, many geometric methods for the prediction of ligand-binding sites have been developed. Results We present LIGSITEcsc, an extension and implementation of the LIGSITE algorithm. LIGSITEcsc is based on the notion of surface-solvent-surface events and the degree of conservation of the involved surface residues. We compare our algorithm to four other approaches, LIGSITE, CAST, PASS, and SURFNET, and evaluate all on a dataset of 48 unbound/bound structures and 210 bound-structures. LIGSITEcsc performs slightly better than the other tools and achieves a success rate of 71% and 75%, respectively. Conclusion The use of the Connolly surface leads to slight improvements, the prediction re-ranking by conservation to significant improvements of the binding site predictions. A web server for LIGSITEcsc and its source code is available at scoppi.biotec.tu-dresden.de/pocket.

  12. Prediction of TF target sites based on atomistic models of protein-DNA complexes

    Directory of Open Access Journals (Sweden)

    Collado-Vides Julio

    2008-10-01

    Full Text Available Abstract Background The specific recognition of genomic cis-regulatory elements by transcription factors (TFs plays an essential role in the regulation of coordinated gene expression. Studying the mechanisms determining binding specificity in protein-DNA interactions is thus an important goal. Most current approaches for modeling TF specific recognition rely on the knowledge of large sets of cognate target sites and consider only the information contained in their primary sequence. Results Here we describe a structure-based methodology for predicting sequence motifs starting from the coordinates of a TF-DNA complex. Our algorithm combines information regarding the direct and indirect readout of DNA into an atomistic statistical model, which is used to estimate the interaction potential. We first measure the ability of our method to correctly estimate the binding specificities of eight prokaryotic and eukaryotic TFs that belong to different structural superfamilies. Secondly, the method is applied to two homology models, finding that sampling of interface side-chain rotamers remarkably improves the results. Thirdly, the algorithm is compared with a reference structural method based on contact counts, obtaining comparable predictions for the experimental complexes and more accurate sequence motifs for the homology models. Conclusion Our results demonstrate that atomic-detail structural information can be feasibly used to predict TF binding sites. The computational method presented here is universal and might be applied to other systems involving protein-DNA recognition.

  13. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan

    2014-07-01

    Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

  14. Predicting active users' personality based on micro-blogging behaviors.

    Science.gov (United States)

    Li, Lin; Li, Ang; Hao, Bibo; Guan, Zengda; Zhu, Tingshao

    2014-01-01

    Because of its richness and availability, micro-blogging has become an ideal platform for conducting psychological research. In this paper, we proposed to predict active users' personality traits through micro-blogging behaviors. 547 Chinese active users of micro-blogging participated in this study. Their personality traits were measured by the Big Five Inventory, and digital records of micro-blogging behaviors were collected via web crawlers. After extracting 839 micro-blogging behavioral features, we first trained classification models utilizing Support Vector Machine (SVM), differentiating participants with high and low scores on each dimension of the Big Five Inventory [corrected]. The classification accuracy ranged from 84% to 92%. We also built regression models utilizing PaceRegression methods, predicting participants' scores on each dimension of the Big Five Inventory. The Pearson correlation coefficients between predicted scores and actual scores ranged from 0.48 to 0.54. Results indicated that active users' personality traits could be predicted by micro-blogging behaviors.

  15. Characterization of the active site properties of CYP4F12.

    Science.gov (United States)

    Eksterowicz, John; Rock, Dan A; Rock, Brooke M; Wienkers, Larry C; Foti, Robert S

    2014-10-01

    Cytochrome P450 4F12 is a drug-metabolizing enzyme that is primarily expressed in the liver, kidney, colon, small intestine, and heart. The properties of CYP4F12 that may impart an increased catalytic selectivity (decreased promiscuity) were explored through in vitro metabolite elucidation, kinetic isotope effect experiments, and computational modeling of the CYP4F12 active site. By using astemizole as a probe substrate for CYP4F12 and CYP3A4, it was observed that although CYP4F12 favored astemizole O-demethylation as the primary route of metabolism, CYP3A4 was capable of metabolizing astemizole at multiple sites on the molecule. Deuteration of astemizole at the site of O-demethylation resulted in an isotope effect of 7.1 as well as an 8.3-fold decrease in the rate of clearance for astemizole by CYP4F12. Conversely, although an isotope effect of 3.8 was observed for the formation of the O-desmethyl metabolite when deuterated astemizole was metabolized by CYP3A4, there was no decrease in the clearance of astemizole. Development of a homology model of CYP4F12 based on the crystal structure of cytochrome P450 BM3 predicted an active site volume for CYP4F12 that was approximately 76% of the active site volume of CYP3A4. As predicted, multiple favorable binding orientations were available for astemizole docked into the active site of CYP3A4, but only a single binding orientation with the site of O-demethylation oriented toward the heme was identified for CYP4F12. Overall, it appears that although CYP4F12 may be capable of binding similar ligands to other cytochrome P450 enzymes such as CYP3A4, the ability to achieve catalytically favorable orientations may be inherently more difficult because of the increased steric constraints of the CYP4F12 active site. PMID:25074871

  16. Big-Five Personality Prediction Based on User Behaviors at Social Network Sites

    CERN Document Server

    Bai, Shuotian; Cheng, Li

    2012-01-01

    Many customer services are already available at Social Network Sites (SNSs), including user recommendation and media interaction, to name a few. There are strong desires to provide online users more dedicated and personalized services that fit into individual's need, usually strongly depending on the inner personalities of the user. However, little has been done to conduct proper psychological analysis, crucial for explaining the user's outer behaviors from their inner personality. In this paper, we propose an approach that intends to facilitate this line of research by directly predicting the so called Big-Five Personality from user's SNS behaviors. Comparing to the conventional inventory-based psychological analysis, we demonstrate via experimental studies that users' personalities can be predicted with reasonable precision based on their online behaviors. Except for proving some former behavior-personality correlation results, our experiments show that extraversion is positively related to one's status rep...

  17. Sequence-based prediction of protein-protein interaction sites with L1-logreg classifier.

    Science.gov (United States)

    Dhole, Kaustubh; Singh, Gurdeep; Pai, Priyadarshini P; Mondal, Sukanta

    2014-05-01

    Protein-protein interactions are of central importance for virtually every process in a living cell. Information about the interaction sites in proteins improves our understanding of disease mechanisms and can provide the basis for new therapeutic approaches. Since a multitude of unique residue-residue contacts facilitate the interactions, protein-protein interaction sites prediction has become one of the most important and challenging problems of computational biology. Although much progress in this field has been reported, this problem is yet to be satisfactorily solved. Here, a novel method (LORIS: L1-regularized LOgistic Regression based protein-protein Interaction Sites predictor) is proposed, that identifies interaction residues, using sequence features and is implemented via the L1-logreg classifier. Results show that LORIS is not only quite effective, but also, performs better than existing state-of-the art methods. LORIS, available as standalone package, can be useful for facilitating drug-design and targeted mutation related studies, which require a deeper knowledge of protein interactions sites. PMID:24486250

  18. HDAC Inhibitors without an Active Site Zn2+-Binding Group

    DEFF Research Database (Denmark)

    Vickers, Chris J.; Olsen, Christian Adam; Leman, Luke J.;

    2012-01-01

    potency against class 1 HDACs and are active in tissue culture against various human cancer cell lines. Importantly, enzymological analysis of 26 indicates that the cyclic α3β-tetrapeptide is a fast-on/ off competitive inhibitor of HDACs 1−3 with Ki values of 49, 33, and 37 nM, respectively. Our proof......Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive their strong binding affinity and high potency from a key functional group that binds to the Zn2+ ion within the enzyme active site. However, this feature is also thought to carry the potential liability of undesirable off......-target interactions with other metalloenzymes. As a step toward mitigating this issue, here, we describe the design, synthesis, and structure−activity characterizations of cyclic α3β-tetrapeptide HDAC inhibitors that lack the presumed indispensable Zn2+-binding group. The lead compounds (e.g., 15 and 26) display good...

  19. Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites

    DEFF Research Database (Denmark)

    Julenius, Karin; Mølgaard, Anne; Gupta, Ramneek;

    2004-01-01

    O-GalNAc-glycosylation is one of the main types of glycosylation in mammalian cells. No consensus recognition sequence for the O-glycosyltransferases is known, making prediction methods necessary to bridge the gap between the large number of known protein sequences and the small number of proteins...... experimentally investigated with regard to glycosylation status. From O-GLYCBASE a total of 86 mammalian proteins experimentally investigated for in vivo O-GalNAc sites were extracted. Mammalian protein homolog comparisons showed that a glycosylated serine or threonine is less likely to be precisely conserved...

  20. Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites

    DEFF Research Database (Denmark)

    Julenius, Karin; Mølgaard, Anne; Gupta, Ramneek;

    2005-01-01

    O-GalNAc-glycosylation is one of the main types of glycosylation in mammalian cells. No consensus recognition sequence for the O-glycosyltransferases is known, making prediction methods necessary to bridge the gap between the large number of known protein sequences and the small number of proteins...... experimentally investigated with regard to glycosylation status. From O-GLYCBASE a total of 86 mammalian proteins experimentally investigated for in vivo O-GalNAc sites were extracted. Mammalian protein homolog comparisons showed that a glycosylated serine or threonine is less likely to be precisely conserved...

  1. Predicting activity approach based on new atoms similarity kernel function.

    Science.gov (United States)

    Abu El-Atta, Ahmed H; Moussa, M I; Hassanien, Aboul Ella

    2015-07-01

    Drug design is a high cost and long term process. To reduce time and costs for drugs discoveries, new techniques are needed. Chemoinformatics field implements the informational techniques and computer science like machine learning and graph theory to discover the chemical compounds properties, such as toxicity or biological activity. This is done through analyzing their molecular structure (molecular graph). To overcome this problem there is an increasing need for algorithms to analyze and classify graph data to predict the activity of molecules. Kernels methods provide a powerful framework which combines machine learning with graph theory techniques. These kernels methods have led to impressive performance results in many several chemoinformatics problems like biological activity prediction. This paper presents a new approach based on kernel functions to solve activity prediction problem for chemical compounds. First we encode all atoms depending on their neighbors then we use these codes to find a relationship between those atoms each other. Then we use relation between different atoms to find similarity between chemical compounds. The proposed approach was compared with many other classification methods and the results show competitive accuracy with these methods.

  2. Platelet serotonin transporter function predicts default-mode network activity.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available The serotonin transporter (5-HTT is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD activity and platelet Vmax.The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.

  3. Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates.

    Directory of Open Access Journals (Sweden)

    Sonu Kumar

    Full Text Available Caspases are enzymes belonging to a conserved family of cysteine-dependent aspartic-specific proteases that are involved in vital cellular processes and play a prominent role in apoptosis and inflammation. Determining all relevant protein substrates of caspases remains a challenging task. Over 1500 caspase substrates have been discovered in the human proteome according to published data and new substrates are discovered on a daily basis. To aid the discovery process we developed a caspase cleavage prediction method using the recently published curated MerCASBA database of experimentally determined caspase substrates and a Random Forest classification method. On both internal and external test sets, the ranking of predicted cleavage positions is superior to all previously developed prediction methods. The in silico predicted caspase cleavage positions in human proteins are available from a relational database: CaspDB. Our database provides information about potential cleavage sites in a verified set of all human proteins collected in Uniprot and their orthologs, allowing for tracing of cleavage motif conservation. It also provides information about the positions of disease-annotated single nucleotide polymorphisms, and posttranslational modifications that may modulate the caspase cleaving efficiency.

  4. IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES).

    Science.gov (United States)

    Kolekar, Pandurang; Pataskar, Abhijeet; Kulkarni-Kale, Urmila; Pal, Jayanta; Kulkarni, Abhijeet

    2016-01-01

    Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5' untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/. PMID:27264539

  5. Current activities handbook: formerly utilized sites remedial action program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-02-27

    This volume is one of a series produced under contract with the DOE, by Politech Corporation to develop a legislative and regulatory data base to assist the FUSRAP management in addressing the institutional and socioeconomic issues involved in carrying out the Formerly Utilized Sites Remedial Action Program. This Information Handbook series contains information about all relevant government agencies at the Federal and state levels, the pertinent programs they administer, each affected state legislature, and current Federal and state legislative and regulatory initiatives. This volume is a compilation of information about the activities each of the thirteen state legislatures potentially affected by the Formerly Utilized Sites Remedial Action Program. It contains a description of the state legislative procedural rules and a schedule of each legislative session; a summary of pending relevant legislation; the name and telephone number of legislative and state agency contacts; and the full text of all bills identified.

  6. Overview of the activities carried out at the FEBEX site

    Energy Technology Data Exchange (ETDEWEB)

    Missana, T.; Buil, B.; Garralon, A.; Gomez, P. [CIEMAT, Dept. de Medioambien te, 28040 Madrid (Spain); Perez-Estaun, A.; Carbonell, R. [Inst. Jaume Almera, CSIC (Spain); Suso, J.; Carretero, G.; Bueno, J.; Martinez, L. [AITEMIN (Spain) ; Hernan, P. [ENRESA (Spain)

    2007-06-15

    One of the main aim of WP 4.1 and 4.2 is to study solute migration mechanisms in crystalline host-rock in realistic conditions. Many organisations are participating in a joint study that is being performed in the FEBEX gallery (NAGRA's Grimsel Test Site, GTS, Switzerland). The FEBEX experiment reproduces at a real scale a high-level waste repository in granite and was installed more than 9 years ago. At moment, it represents the most realistic environment where the processes affecting radionuclide migration from the bentonite to granite can be studied. This paper summarises the main activities carried out at the FEBEX site during the second year of the project.

  7. Current activities handbook: formerly utilized sites remedial action program

    International Nuclear Information System (INIS)

    This volume is one of a series produced under contract with the DOE, by Politech Corporation to develop a legislative and regulatory data base to assist the FUSRAP management in addressing the institutional and socioeconomic issues involved in carrying out the Formerly Utilized Sites Remedial Action Program. This Information Handbook series contains information about all relevant government agencies at the Federal and state levels, the pertinent programs they administer, each affected state legislature, and current Federal and state legislative and regulatory initiatives. This volume is a compilation of information about the activities each of the thirteen state legislatures potentially affected by the Formerly Utilized Sites Remedial Action Program. It contains a description of the state legislative procedural rules and a schedule of each legislative session; a summary of pending relevant legislation; the name and telephone number of legislative and state agency contacts; and the full text of all bills identified

  8. Active diagnosis of hybrid systems - A model predictive approach

    DEFF Research Database (Denmark)

    Tabatabaeipour, Seyed Mojtaba; Ravn, Anders P.; Izadi-Zamanabadi, Roozbeh;

    2009-01-01

    A method for active diagnosis of hybrid systems is proposed. The main idea is to predict the future output of both normal and faulty model of the system; then at each time step an optimization problem is solved with the objective of maximizing the difference between the predicted normal and faulty...... outputs constrained by tolerable performance requirements. As in standard model predictive control, the first element of the optimal input is applied to the system and the whole procedure is repeated until the fault is detected by a passive diagnoser. It is demonstrated how the generated excitation signal...... can be used as a test signal for sanity check at the commissioning or for detection of faults hidden by regulatory actions of the controller. The method is tested on the two tank benchmark example. ©2009 IEEE....

  9. Predictive Models for Halogen-bond Basicity of Binding Sites of Polyfunctional Molecules.

    Science.gov (United States)

    Glavatskikh, Marta; Madzhidov, Timur; Solov'ev, Vitaly; Marcou, Gilles; Horvath, Dragos; Graton, Jérôme; Le Questel, Jean-Yves; Varnek, Alexandre

    2016-02-01

    Halogen bonding (XB) strength assesses the ability of an electron-enriched group to be involved in complexes with polarizable electrophilic halogenated or diatomic halogen molecules. Here, we report QSPR models of XB of particular relevance for an efficient screening of large sets of compounds. The basicity is described by pKBI2 , the decimal logarithm of the experimental 1 : 1 (B : I2 ) complexation constant K of organic compounds (B) with diiodine (I2 ) as a reference halogen-bond donor in alkanes at 298 K. Modeling involved ISIDA fragment descriptors, using SVM and MLR methods on a set of 598 organic compounds. Developed models were then challenged to make predictions for an external test set of 11 polyfunctional compounds for which unambiguous assignment of the measured effective complexation constant to specific groups out of the putative acceptor sites is not granted. At this stage, developed models were used to predict pKBI2 of all putative acceptor sites, followed by an estimation of the predicted effective complexation constant using the ChemEqui program. The best consensus models perform well both in cross-validation (root mean squared error RMSE=0.39-0.47 logKBI2 units) and external predictions (RMSE=0.49). The SVM models are implemented on our website (http://infochim.u-strasbg.fr/webserv/VSEngine.html) together with the estimation of their applicability domain and an automatic detection of potential halogen-bond acceptor atoms. PMID:27491792

  10. A Cascade Random Forests Algorithm for Predicting Protein-Protein Interaction Sites.

    Science.gov (United States)

    Wei, Zhi-Sen; Yang, Jing-Yu; Shen, Hong-Bin; Yu, Dong-Jun

    2015-10-01

    Protein-protein interactions exist ubiquitously and play important roles in the life cycles of living cells. The interaction sites (residues) are essential to understanding the underlying mechanisms of protein-protein interactions. Previous research has demonstrated that the accurate identification of protein-protein interaction sites (PPIs) is helpful for developing new therapeutic drugs because many drugs will interact directly with those residues. Because of its significant potential in biological research and drug development, the prediction of PPIs has become an important topic in computational biology. However, a severe data imbalance exists in the PPIs prediction problem, where the number of the majority class samples (non-interacting residues) is far larger than that of the minority class samples (interacting residues). Thus, we developed a novel cascade random forests algorithm (CRF) to address the serious data imbalance that exists in the PPIs prediction problem. The proposed CRF resolves the negative effect of data imbalance by connecting multiple random forests in a cascade-like manner, each of which is trained with a balanced training subset that includes all minority samples and a subset of majority samples using an effective ensemble protocol. Based on the proposed CRF, we implemented a new sequence-based PPIs predictor, called CRF-PPI, which takes the combined features of position-specific scoring matrices, averaged cumulative hydropathy, and predicted relative solvent accessibility as model inputs. Benchmark experiments on both the cross validation and independent validation datasets demonstrated that the proposed CRF-PPI outperformed the state-of-the-art sequence-based PPIs predictors. The source code for CRF-PPI and the benchmark datasets are available online at http://csbio.njust.edu.cn/bioinf/CRF-PPI for free academic use. PMID:26441427

  11. Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model.

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Huang

    Full Text Available Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with

  12. Prediction of S-Nitrosylation Modification Sites Based on Kernel Sparse Representation Classification and mRMR Algorithm

    Directory of Open Access Journals (Sweden)

    Guohua Huang

    2014-01-01

    Full Text Available Protein S-nitrosylation plays a very important role in a wide variety of cellular biological activities. Hitherto, accurate prediction of S-nitrosylation sites is still of great challenge. In this paper, we presented a framework to computationally predict S-nitrosylation sites based on kernel sparse representation classification and minimum Redundancy Maximum Relevance algorithm. As much as 666 features derived from five categories of amino acid properties and one protein structure feature are used for numerical representation of proteins. A total of 529 protein sequences collected from the open-access databases and published literatures are used to train and test our predictor. Computational results show that our predictor achieves Matthews’ correlation coefficients of 0.1634 and 0.2919 for the training set and the testing set, respectively, which are better than those of k-nearest neighbor algorithm, random forest algorithm, and sparse representation classification algorithm. The experimental results also indicate that 134 optimal features can better represent the peptides of protein S-nitrosylation than the original 666 redundant features. Furthermore, we constructed an independent testing set of 113 protein sequences to evaluate the robustness of our predictor. Experimental result showed that our predictor also yielded good performance on the independent testing set with Matthews’ correlation coefficients of 0.2239.

  13. Neural activity during encoding predicts false memories created by misinformation

    OpenAIRE

    Okado, Yoko; Stark, Craig E.L.

    2005-01-01

    False memories are often demonstrated using the misinformation paradigm, in which a person's recollection of a witnessed event is altered after exposure to misinformation about the event. The neural basis of this phenomenon, however, remains unknown. We used fMRI to investigate encoding processes during the viewing of an event and misinformation to see whether neural activity during either encoding phase could predict what would be remembered. fMRI data were collected as participants studied ...

  14. Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

    OpenAIRE

    Christian Scharinger; Ulrich Rabl; Christian H. Kasess; Meyer, Bernhard M.; Tina Hofmaier; Kersten Diers; Lucie Bartova; Gerald Pail; Wolfgang Huf; Zeljko Uzelac; Beate Hartinger; Klaudius Kalcher; Thomas Perkmann; Helmuth Haslacher; Andreas Meyer-Lindenberg

    2014-01-01

    Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy...

  15. Resource assurance predicts specialist and generalist bee activity in drought

    OpenAIRE

    Minckley, Robert L.; Roulston, T'ai H.; Williams, Neal M.

    2013-01-01

    Many short-lived desert organisms remain in diapause during drought. Theoretically, the cues desert species use to continue diapause through drought should differ depending on the availability of critical resources, but the unpredictability and infrequent occurrence of climate extremes and reduced insect activity during such events make empirical tests of this prediction difficult. An intensive study of a diverse bee–plant community through a drought event found that bee specialists of a drou...

  16. Oxygen reduction and evolution at single-metal active sites

    DEFF Research Database (Denmark)

    Calle-Vallejo, F.; Martínez, J.I.; García Lastra, Juan Maria;

    2013-01-01

    A worldwide spread of clean technologies such as low-temperature fuel cells and electrolyzers depends strictly on their technical reliability and economic affordability. Currently, both conditions are hardly fulfilled mainly due to the same reason: the oxygen electrode, which has large overpotent...... may be improved by careful selections of the support and the ligand properties close to the active sites and/or the ramifications near them, so that charge is transferred back and forth during adsorption and selective hydrogen bonds are formed....

  17. 10 CFR 63.16 - Review of site characterization activities. 2

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Review of site characterization activities. 2 63.16... site characterization activities. 2 2 In addition to the review of site characterization activities... investigation and site characterization, to allow early identification of potential licensing issues for...

  18. Improving active space telescope wavefront control using predictive thermal modeling

    Science.gov (United States)

    Gersh-Range, Jessica; Perrin, Marshall D.

    2015-01-01

    Active control algorithms for space telescopes are less mature than those for large ground telescopes due to differences in the wavefront control problems. Active wavefront control for space telescopes at L2, such as the James Webb Space Telescope (JWST), requires weighing control costs against the benefits of correcting wavefront perturbations that are a predictable byproduct of the observing schedule, which is known and determined in advance. To improve the control algorithms for these telescopes, we have developed a model that calculates the temperature and wavefront evolution during a hypothetical mission, assuming the dominant wavefront perturbations are due to changes in the spacecraft attitude with respect to the sun. Using this model, we show that the wavefront can be controlled passively by introducing scheduling constraints that limit the allowable attitudes for an observation based on the observation duration and the mean telescope temperature. We also describe the implementation of a predictive controller designed to prevent the wavefront error (WFE) from exceeding a desired threshold. This controller outperforms simpler algorithms even with substantial model error, achieving a lower WFE without requiring significantly more corrections. Consequently, predictive wavefront control based on known spacecraft attitude plans is a promising approach for JWST and other future active space observatories.

  19. Feature selection for splice site prediction: A new method using EDA-based feature ranking

    Directory of Open Access Journals (Sweden)

    Rouzé Pierre

    2004-05-01

    Full Text Available Abstract Background The identification of relevant biological features in large and complex datasets is an important step towards gaining insight in the processes underlying the data. Other advantages of feature selection include the ability of the classification system to attain good or even better solutions using a restricted subset of features, and a faster classification. Thus, robust methods for fast feature selection are of key importance in extracting knowledge from complex biological data. Results In this paper we present a novel method for feature subset selection applied to splice site prediction, based on estimation of distribution algorithms, a more general framework of genetic algorithms. From the estimated distribution of the algorithm, a feature ranking is derived. Afterwards this ranking is used to iteratively discard features. We apply this technique to the problem of splice site prediction, and show how it can be used to gain insight into the underlying biological process of splicing. Conclusion We show that this technique proves to be more robust than the traditional use of estimation of distribution algorithms for feature selection: instead of returning a single best subset of features (as they normally do this method provides a dynamical view of the feature selection process, like the traditional sequential wrapper methods. However, the method is faster than the traditional techniques, and scales better to datasets described by a large number of features.

  20. 77 FR 39508 - Commercial Wind Lease Issuance and Site Assessment Activities on the Atlantic Outer Continental...

    Science.gov (United States)

    2012-07-03

    ... characterization activities (geophysical, geotechnical, archaeological, and biological surveys needed to develop..., site characterization, and site assessment in and around the Call Area (76 FR 51391). The Call Area...

  1. Probing the putative active site of YjdL

    DEFF Research Database (Denmark)

    Jensen, Johanne Mørch; Ismat, Fouzia; Szakonyi, Gerda;

    2012-01-01

    YjdL from E. coli is an unusual proton-coupled oligopeptide transporter (POT). Unlike prototypical POTs, dipeptides are preferred over tripeptides, in particular dipeptides with a positively charged C-terminal residue. To further understand this difference in peptide specificity, the sequences...... of YjdL and YdgR, a prototypical E. coli POT, were compared in light of the crystal structure of a POT from Shewanella oneidensis. Several residues found in the putative active site were mutated and the activities of the mutated variants were assessed in terms of substrate uptake assays, and changes...... pocket that opens towards the extracellular space. The C-terminal side chain faces in the opposite direction into a sub pocket that faces the cytoplasm. These data indicated a stabilizing effect on a bulky N-terminal residue by an Ala281Phe variant and on the dipeptide backbone by Trp278...

  2. Predicting success of oligomerized pool engineering (OPEN for zinc finger target site sequences

    Directory of Open Access Journals (Sweden)

    Goodwin Mathew J

    2010-11-01

    Full Text Available Abstract Background Precise and efficient methods for gene targeting are critical for detailed functional analysis of genomes and regulatory networks and for potentially improving the efficacy and safety of gene therapies. Oligomerized Pool ENgineering (OPEN is a recently developed method for engineering C2H2 zinc finger proteins (ZFPs designed to bind specific DNA sequences with high affinity and specificity in vivo. Because generation of ZFPs using OPEN requires considerable effort, a computational method for identifying the sites in any given gene that are most likely to be successfully targeted by this method is desirable. Results Analysis of the base composition of experimentally validated ZFP target sites identified important constraints on the DNA sequence space that can be effectively targeted using OPEN. Using alternate encodings to represent ZFP target sites, we implemented Naïve Bayes and Support Vector Machine classifiers capable of distinguishing "active" targets, i.e., ZFP binding sites that can be targeted with a high rate of success, from those that are "inactive" or poor targets for ZFPs generated using current OPEN technologies. When evaluated using leave-one-out cross-validation on a dataset of 135 experimentally validated ZFP target sites, the best Naïve Bayes classifier, designated ZiFOpT, achieved overall accuracy of 87% and specificity+ of 90%, with an ROC AUC of 0.89. When challenged with a completely independent test set of 140 newly validated ZFP target sites, ZiFOpT performance was comparable in terms of overall accuracy (88% and specificity+ (92%, but with reduced ROC AUC (0.77. Users can rank potentially active ZFP target sites using a confidence score derived from the posterior probability returned by ZiFOpT. Conclusion ZiFOpT, a machine learning classifier trained to identify DNA sequences amenable for targeting by OPEN-generated zinc finger arrays, can guide users to target sites that are most likely to function

  3. Virtual Screening and Prediction of Site of Metabolism for Cytochrome P450 1A2 Ligands

    DEFF Research Database (Denmark)

    Vasanthanathan, P.; Hritz, Jozef; Taboureau, Olivier;

    2009-01-01

    questions have been addressed: 1. Binding orientations and conformations were successfully predicted for various substrates. 2. A virtual screen was performed with satisfying enrichment rates. 3. A classification of individual compounds into active and inactive was performed. It was found that while docking...... and earlier classification data using machine learning methods. The possibilities and limitations of using structure-based drug design tools for cytochrome P450 1A2 come to light and are discussed....

  4. Computational Prediction of O-linked Glycosylation Sites that Preferentially Map on Intrinsically Disordered Regions of Extracellular Proteins

    Directory of Open Access Journals (Sweden)

    Satoshi Fukuchi

    2010-12-01

    Full Text Available O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.

  5. Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer

    Science.gov (United States)

    Dinpajooh, Mohammadhasan; Martin, Daniel R.; Matyushov, Dmitry V.

    2016-06-01

    Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work.

  6. Perchlorate Reductase Is Distinguished by Active Site Aromatic Gate Residues.

    Science.gov (United States)

    Youngblut, Matthew D; Tsai, Chi-Lin; Clark, Iain C; Carlson, Hans K; Maglaqui, Adrian P; Gau-Pan, Phonchien S; Redford, Steven A; Wong, Alan; Tainer, John A; Coates, John D

    2016-04-22

    Perchlorate is an important ion on both Earth and Mars. Perchlorate reductase (PcrAB), a specialized member of the dimethylsulfoxide reductase superfamily, catalyzes the first step of microbial perchlorate respiration, but little is known about the biochemistry, specificity, structure, and mechanism of PcrAB. Here we characterize the biophysics and phylogeny of this enzyme and report the 1.86-Å resolution PcrAB complex crystal structure. Biochemical analysis revealed a relatively high perchlorate affinity (Km = 6 μm) and a characteristic substrate inhibition compared with the highly similar respiratory nitrate reductase NarGHI, which has a relatively much lower affinity for perchlorate (Km = 1.1 mm) and no substrate inhibition. Structural analysis of oxidized and reduced PcrAB with and without the substrate analog SeO3 (2-) bound to the active site identified key residues in the positively charged and funnel-shaped substrate access tunnel that gated substrate entrance and product release while trapping transiently produced chlorate. The structures suggest gating was associated with shifts of a Phe residue between open and closed conformations plus an Asp residue carboxylate shift between monodentate and bidentate coordination to the active site molybdenum atom. Taken together, structural and mutational analyses of gate residues suggest key roles of these gate residues for substrate entrance and product release. Our combined results provide the first detailed structural insight into the mechanism of biological perchlorate reduction, a critical component of the chlorine redox cycle on Earth.

  7. Maxey Flats low-level waste disposal site closure activities

    International Nuclear Information System (INIS)

    The Maxey Flats Radioactive Waste Disposal Facility in Fleming County, Kentucky is in the process of being closed. The facility opened for commercial business in the spring of 1963 and received approximately 4.75 million cubic feet of radioactive waste by the time it was closed in December of 1977. During fourteen years of operation approximately 2.5 million curies of by-product material, 240,000 kilograms of source material, and 430 kilograms of special nuclear material were disposed. The Commonwealth purchased the lease hold estate and rights in May 1978 from the operating company. This action was taken to stabilize the facility and prepare it for closure consisting of passive care and monitoring. To prepare the site for closure, a number of remedial activities had to be performed. The remediation activities implemented have included erosion control, surface drainage modifications, installation of a temporary plastic surface cover, leachate removal, analysis, treatment and evaporation, US DOE funded evaporator concentrates solidification project and their on-site disposal in an improved disposal trench with enhanced cover for use in a humid environment situated in a fractured geology, performance evaluation of a grout injection demonstration, USGS subsurface geologic investigation, development of conceptual closure designs, and finally being added to the US EPA National Priority List for remediation and closure under Superfund. 13 references, 3 figures

  8. Identification of covalent active site inhibitors of dengue virus protease

    Directory of Open Access Journals (Sweden)

    Koh-Stenta X

    2015-12-01

    Full Text Available Xiaoying Koh-Stenta,1 Joma Joy,1 Si Fang Wang,1 Perlyn Zekui Kwek,1 John Liang Kuan Wee,1 Kah Fei Wan,2 Shovanlal Gayen,1 Angela Shuyi Chen,1 CongBao Kang,1 May Ann Lee,1 Anders Poulsen,1 Subhash G Vasudevan,3 Jeffrey Hill,1 Kassoum Nacro11Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR, Singapore; 2Novartis Institute for Tropical Diseases, Singapore; 3Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, SingaporeAbstract: Dengue virus (DENV protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and protease-inhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described.Keywords: flavivirus protease, small molecule optimization, covalent inhibitor, active site binding, pyrazole ester derivatives

  9. Insight into the mechanism of phosphoenolpyruvate mutase catalysis derived from site-directed mutagenesis studies of active site residues.

    Science.gov (United States)

    Jia, Y; Lu, Z; Huang, K; Herzberg, O; Dunaway-Mariano, D

    1999-10-26

    PEP mutase catalyzes the conversion of phosphoenolpyruvate (PEP) to phosphonopyruvate in biosynthetic pathways leading to phosphonate secondary metabolites. A recent X-ray structure [Huang, K., Li, Z., Jia, Y., Dunaway-Mariano, D., and Herzberg, O. (1999) Structure (in press)] of the Mytilus edulis enzyme complexed with the Mg(II) cofactor and oxalate inhibitor reveals an alpha/beta-barrel backbone-fold housing an active site in which Mg(II) is bound by the two carboxylate groups of the oxalate ligand and the side chain of D85 and, via bridging water molecules, by the side chains of D58, D85, D87, and E114. The oxalate ligand, in turn, interacts with the side chains of R159, W44, and S46 and the backbone amide NHs of G47 and L48. Modeling studies identified two feasible PEP binding modes: model A in which PEP replaces oxalate with its carboxylate group interacting with R159 and its phosphoryl group positioned close to D58 and Mg(II) shifting slightly from its original position in the crystal structure, and model B in which PEP replaces oxalate with its phosphoryl group interacting with R159 and Mg(II) retaining its original position. Site-directed mutagenesis studies of the key mutase active site residues (R159, D58, D85, D87, and E114) were carried out in order to evaluate the catalytic roles predicted by the two models. The observed retention of low catalytic activity in the mutants R159A, D85A, D87A, and E114A, coupled with the absence of detectable catalytic activity in D58A, was interpreted as evidence for model A in which D58 functions in nucleophilic catalysis (phosphoryl transfer), R159 functions in PEP carboxylate group binding, and the carboxylates of D85, D87 and E114 function in Mg(II) binding. These results also provide evidence against model B in which R159 serves to mediate the phosphoryl transfer. A catalytic motif, which could serve both the phosphoryl transfer and the C-C cleavage enzymes of the PEP mutase superfamily, is proposed. PMID:10571990

  10. Integrated Model of DNA Sequence Numerical Representation and Artificial Neural Network for Human Donor and Acceptor Sites Prediction

    Directory of Open Access Journals (Sweden)

    Mohammed Abo-Zahhad

    2014-07-01

    Full Text Available Human Genome Project has led to a huge inflow of genomic data. After the completion of human genome sequencing, more and more effort is being put into identification of splicing sites of exons and introns (donor and acceptor sites. These invite bioinformatics to analysis the genome sequences and identify the location of exon and intron boundaries or in other words prediction of splicing sites. Prediction of splice sites in genic regions of DNA sequence is one of the most challenging aspects of gene structure recognition. Over the last two decades, artificial neural networks gradually became one of the essential tools in bioinformatics. In this paper artificial neural networks with different numerical mapping techniques have been employed for building integrated model for splice site prediction in genes. An artificial neural network is trained and then used to find splice sites in human genes. A comparison between different mapping methods using trained neural network in terms of their precision in prediction of donor and acceptor sites will be presented in this paper. Training and measuring performance of neural network are carried out using sequences of the human genome (GRch37/hg19- chr21. Simulation results indicate that using Electron-Ion Interaction Potential numerical mapping method with neural network yields to the best performance in prediction.

  11. Meteorological predictions for Mars 2020 Exploration Rover high-priority landing sites throug MRAMS Mesoscale Modeling

    Science.gov (United States)

    Pla-García, Jorge; Rafkin, Scot C. R.

    2015-04-01

    The Mars Regional Atmospheric Modeling System (MRAMS) is used to predict meteorological conditions that are likely to be encountered by the Mars 2020 Exploration Rover at several proposed landing sites during entry, descent, and landing (EDL). The meteorology during the EDL window at most of the sites is dynamic. The intense heating of the lower atmosphere drives intense thermals and mesoscale thermal circulations. Moderate mean winds, wind shear, turbulence, and vertical air currents associated with convection are present and potentially hazardous to EDL [1]. Nine areas with specific high-priority landing ellipses of the 2020 Rover, are investigated: NE Syrtis, Nili Fossae, Nili Fossae Carbonates, Jezero Crater Delta, Holden Crater, McLaughlin Crater, Southwest Melas Basin, Mawrth Vallis and East Margaritifer Chloride. MRAMS was applied to the landing site regions using nested grids with a spacing of 330 meters on the innermost grid that is centered over each landing site. MRAMS is ideally suited for this investigation; the model is explicitly designed to simulate Mars' atmospheric thermal circulations at the mesoscale and smaller with realistic, high-resolution surface properties [2, 3]. Horizontal wind speeds, both vertical profiles and vertical cross-sections wind speeds, are studied. For some landing sites simulations, two example configurations -including and not including Hellas basin in the mother domain- were generated, in order to study how the basin affects the innermost grids circulations. Afternoon circulations at all sites pose some risk entry, descent, and landing. Most of the atmospheric hazards are not evident in current observational data and general circulation model simulations and can only be ascertained through mesoscale modeling of the region. Decide where to go first and then design a system that can tolerate the environment would greatly minimize risk. References: [1] Rafkin, S. C. R., and T. I. Michaels (2003), J. Geophys. Res., 108(E12

  12. The Las Cruces Trench Site: Characterization, Experimental Results, and One-Dimensional Flow Predictions

    Science.gov (United States)

    Wierenga, P. J.; Hills, R. G.; Hudson, D. B.

    1991-10-01

    the layered soil model rather than the uniform soil model does not consistently improve the accuracy of the predictions for this particular field application. This result illustrates that increasing the spatial resolution of the deterministic characterization of the site in the vertical direction does not always improve the model predictions. Uncertainties due to horizontal spatial variability and due to other difficulties associated with experimental characterization appear to be more significant.

  13. Predicting flow at work: investigating the activities and job characteristics that predict flow states at work.

    Science.gov (United States)

    Nielsen, Karina; Cleal, Bryan

    2010-04-01

    Flow (a state of consciousness where people become totally immersed in an activity and enjoy it intensely) has been identified as a desirable state with positive effects for employee well-being and innovation at work. Flow has been studied using both questionnaires and Experience Sampling Method (ESM). In this study, we used a newly developed 9-item flow scale in an ESM study combined with a questionnaire to examine the predictors of flow at two levels: the activities (brainstorming, planning, problem solving and evaluation) associated with transient flow states and the more stable job characteristics (role clarity, influence and cognitive demands). Participants were 58 line managers from two companies in Denmark; a private accountancy firm and a public elder care organization. We found that line managers in elder care experienced flow more often than accountancy line managers, and activities such as planning, problem solving, and evaluation predicted transient flow states. The more stable job characteristics included in this study were not, however, found to predict flow at work.

  14. Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426.

    Science.gov (United States)

    Zhang, Yu; An, Jiao; Yang, Guang-Yu; Bai, Aixi; Zheng, Baisong; Lou, Zhiyong; Wu, Geng; Ye, Wei; Chen, Hai-Feng; Feng, Yan; Manco, Giuseppe

    2015-01-01

    Enzyme promiscuity is a prerequisite for fast divergent evolution of biocatalysts. A phosphotriesterase-like lactonase (PLL) from Geobacillus kaustophilus HTA426 (GkaP) exhibits main lactonase and promiscuous phosphotriesterase activities. To understand its catalytic and evolutionary mechanisms, we investigated a "hot spot" in the active site by saturation mutagenesis as well as X-ray crystallographic analyses. We found that position 99 in the active site was involved in substrate discrimination. One mutant, Y99L, exhibited 11-fold improvement over wild-type in reactivity (kcat/Km) toward the phosphotriesterase substrate ethyl-paraoxon, but showed 15-fold decrease toward the lactonase substrate δ-decanolactone, resulting in a 157-fold inversion of the substrate specificity. Structural analysis of Y99L revealed that the mutation causes a ∼6.6 Å outward shift of adjacent loop 7, which may cause increased flexibility of the active site and facilitate accommodation and/or catalysis of organophosphate substrate. This study provides for the PLL family an example of how the evolutionary route from promiscuity to specificity can derive from very few mutations, which promotes alteration in the conformational adjustment of the active site loops, in turn draws the capacity of substrate binding and activity.

  15. Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426.

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    Full Text Available Enzyme promiscuity is a prerequisite for fast divergent evolution of biocatalysts. A phosphotriesterase-like lactonase (PLL from Geobacillus kaustophilus HTA426 (GkaP exhibits main lactonase and promiscuous phosphotriesterase activities. To understand its catalytic and evolutionary mechanisms, we investigated a "hot spot" in the active site by saturation mutagenesis as well as X-ray crystallographic analyses. We found that position 99 in the active site was involved in substrate discrimination. One mutant, Y99L, exhibited 11-fold improvement over wild-type in reactivity (kcat/Km toward the phosphotriesterase substrate ethyl-paraoxon, but showed 15-fold decrease toward the lactonase substrate δ-decanolactone, resulting in a 157-fold inversion of the substrate specificity. Structural analysis of Y99L revealed that the mutation causes a ∼6.6 Å outward shift of adjacent loop 7, which may cause increased flexibility of the active site and facilitate accommodation and/or catalysis of organophosphate substrate. This study provides for the PLL family an example of how the evolutionary route from promiscuity to specificity can derive from very few mutations, which promotes alteration in the conformational adjustment of the active site loops, in turn draws the capacity of substrate binding and activity.

  16. Prediction and Analysis of Post-Translational Pyruvoyl Residue Modification Sites from Internal Serines in Proteins.

    Directory of Open Access Journals (Sweden)

    Yang Jiang

    Full Text Available Most of pyruvoyl-dependent proteins observed in prokaryotes and eukaryotes are critical regulatory enzymes, which are primary targets of inhibitors for anti-cancer and anti-parasitic therapy. These proteins undergo an autocatalytic, intramolecular self-cleavage reaction in which a covalently bound pyruvoyl group is generated on a conserved serine residue. Traditional detections of the modified serine sites are performed by experimental approaches, which are often labor-intensive and time-consuming. In this study, we initiated in an attempt for the computational predictions of such serine sites with Feature Selection based on a Random Forest. Since only a small number of experimentally verified pyruvoyl-modified proteins are collected in the protein database at its current version, we only used a small dataset in this study. After removing proteins with sequence identities >60%, a non-redundant dataset was generated and was used, which contained only 46 proteins, with one pyruvoyl serine site for each protein. Several types of features were considered in our method including PSSM conservation scores, disorders, secondary structures, solvent accessibilities, amino acid factors and amino acid occurrence frequencies. As a result, a pretty good performance was achieved in our dataset. The best 100.00% accuracy and 1.0000 MCC value were obtained from the training dataset, and 93.75% accuracy and 0.8441 MCC value from the testing dataset. The optimal feature set contained 9 features. Analysis of the optimal feature set indicated the important roles of some specific features in determining the pyruvoyl-group-serine sites, which were consistent with several results of earlier experimental studies. These selected features may shed some light on the in-depth understanding of the mechanism of the post-translational self-maturation process, providing guidelines for experimental validation. Future work should be made as more pyruvoyl-modified proteins are

  17. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    Directory of Open Access Journals (Sweden)

    Łukasz Pałkowski

    2015-01-01

    Full Text Available The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA, which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds.

  18. Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae

    Directory of Open Access Journals (Sweden)

    Hasnain Seyed

    2004-09-01

    Full Text Available Abstract Background The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae. Result Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG, an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. Conclusions We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase

  19. ChloroP, a neural network-based method for predicting chloroplast transitpeptides and their cleavage sites

    DEFF Research Database (Denmark)

    Emanuelsson, O.; Nielsen, Henrik; von Heijne, Gunnar

    1999-01-01

    We present a neural network based method (ChloroP) for identifying chloroplast transit peptides and their cleavage sites. Using cross-validation, 88% of the sequences in our homology reduced training set were correctly classified as transit peptides or nontransit peptides. This performance level...... is well above that of the publicly available chloroplast localization predictor PSORT. Cleavage sites are predicted using a scoring matrix derived by an automatic motif-finding algorithm. Approximately 60% of the known cleavage sites in our sequence collection were predicted to within +/-2 residues from...

  20. Metals in the active site of native protein phosphatase-1.

    Science.gov (United States)

    Heroes, Ewald; Rip, Jens; Beullens, Monique; Van Meervelt, Luc; De Gendt, Stefan; Bollen, Mathieu

    2015-08-01

    Protein phosphatase-1 (PP1) is a major protein Ser/Thr phosphatase in eukaryotic cells. Its activity depends on two metal ions in the catalytic site, which were identified as manganese in the bacterially expressed phosphatase. However, the identity of the metal ions in native PP1 is unknown. In this study, total reflection X-ray fluorescence (TXRF) was used to detect iron and zinc in PP1 that was purified from rabbit skeletal muscle. Metal exchange experiments confirmed that the distinct substrate specificity of recombinant and native PP1 is determined by the nature of their associated metals. We also found that the iron level associated with native PP1 is decreased by incubation with inhibitor-2, consistent with a function of inhibitor-2 as a PP1 chaperone. PMID:25890482

  1. Building gene expression signatures indicative of transcription factor activation to predict AOP modulation

    Science.gov (United States)

    Building gene expression signatures indicative of transcription factor activation to predict AOP modulation Adverse outcome pathways (AOPs) are a framework for predicting quantitative relationships between molecular initiatin...

  2. QUANTITATIVE STRUCTURE—PROPERTY RELATIONSHIPS FOR ENHANCING PREDICTIONS OF SYNTHETIC ORGANIC CHEMICAL REMOVAL FROM DRINKING WATER BY GRANULAR ACTIVATED CARBON

    Science.gov (United States)

    A number of mathematical models have been developed to predict activated carbon column performance using single-solute isotherm data as inputs. Many assumptions are built into these models to account for kinetics of adsorption and competition for adsorption sites. This work...

  3. Metavanadate at the active site of the phosphatase VHZ.

    Science.gov (United States)

    Kuznetsov, Vyacheslav I; Alexandrova, Anastassia N; Hengge, Alvan C

    2012-09-01

    Vanadate is a potent modulator of a number of biological processes and has been shown by crystal structures and NMR spectroscopy to interact with numerous enzymes. Although these effects often occur under conditions where oligomeric forms dominate, the crystal structures and NMR data suggest that the inhibitory form is usually monomeric orthovanadate, a particularly good inhibitor of phosphatases because of its ability to form stable trigonal-bipyramidal complexes. We performed a computational analysis of a 1.14 Å structure of the phosphatase VHZ in complex with an unusual metavanadate species and compared it with two classical trigonal-bipyramidal vanadate-phosphatase complexes. The results support extensive delocalized bonding to the apical ligands in the classical structures. In contrast, in the VHZ metavanadate complex, the central, planar VO(3)(-) moiety has only one apical ligand, the nucleophilic Cys95, and a gap in electron density between V and S. A computational analysis showed that the V-S interaction is primarily ionic. A mechanism is proposed to explain the formation of metavanadate in the active site from a dimeric vanadate species that previous crystallographic evidence has shown to be able to bind to the active sites of phosphatases related to VHZ. Together, the results show that the interaction of vanadate with biological systems is not solely reliant upon the prior formation of a particular inhibitory form in solution. The catalytic properties of an enzyme may act upon the oligomeric forms primarily present in solution to generate species such as the metavanadate ion observed in the VHZ structure. PMID:22876963

  4. Prediction of evacuation time for emergency planning zone of Uljin nuclear site

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, In Young; Lee, Jai Ki [Hanyang Univ., Seoul (Korea, Republic of)

    2002-09-15

    The time for evacuation of residents in Emergency Planning Zone (EPZ) of Uljin nuclear site in case of a radiological emergency was estimated with traffic analysis. Evacuees were classified into 4 groups by considering population density, local jurisdictions, and whether they are residents or transients. The survey to investigate the behavioral characteristics of the residents was made for 200 households and included a hypothetical scenario explaining the accident situation and questions such as dwelling place, time demand for evacuation preparation, transportation means for evacuation, sheltering place, and evacuation direction. The microscopic traffic simulation model, CORSIM, was used to simulate the behavior of evacuating vehicles on networks. The results showed that the evacuation time required for total vehicles to move out from EPZ took longer in the daytime than at night in spite that the delay times at intersections were longer at night than in the daytime. This was analyzed due to the differences of the trip generation time distribution. To validate whether the CORSIM model can appropriately simulate the congested traffic phenomena assumable in case of emergency, a benchmark study was conducted at an intersection without an actuated traffic signal near Uljin site during the traffic peak-time in the morning. This study indicated that the predicted output by the CORSIM model was in good agreement with the observed data, satisfying the purpose of this study.

  5. Prediction of Water Binding to Protein Hydration Sites with a Discrete, Semiexplicit Solvent Model.

    Science.gov (United States)

    Setny, Piotr

    2015-12-01

    Buried water molecules are ubiquitous in protein structures and are found at the interface of most protein-ligand complexes. Determining their distribution and thermodynamic effect is a challenging yet important task, of great of practical value for the modeling of biomolecular structures and their interactions. In this study, we present a novel method aimed at the prediction of buried water molecules in protein structures and estimation of their binding free energies. It is based on a semiexplicit, discrete solvation model, which we previously introduced in the context of small molecule hydration. The method is applicable to all macromolecular structures described by a standard all-atom force field, and predicts complete solvent distribution within a single run with modest computational cost. We demonstrate that it indicates positions of buried hydration sites, including those filled by more than one water molecule, and accurately differentiates them from sterically accessible to water but void regions. The obtained estimates of water binding free energies are in fair agreement with reference results determined with the double decoupling method. PMID:26642995

  6. A Text Analysis Based Seamless Framework for Predicting Human Personality Traits from Social Networking Sites

    Directory of Open Access Journals (Sweden)

    Harish Kumar

    2012-09-01

    Full Text Available Predicting human behavior based on the usage of text on social networking sites can be a challenging area of interest to a particular community. Text mining being a major interest in Data Mining has vast applications in various fields. Clients can assess an individual’s behavior using the proposed framework that is based on person’s textual interaction with other people. In this paper, a framework is proposed for predicting human behavior in three phases- Text Extraction, Text cleaning and Text Analysis. For cleaning text, all the stop words have been removed and then the text is utilized for further processing. Then, the terms from the text are clustered based on semantic similarity and then gets associated with respective physiological parameters that identify a human behavior. This application is best suited for the fields of Criminal Sciences, Medical Sciences, Human Resource Department and Political Science and even for Matrimonial purposes. The proposed framework is applied on some famous world known celebrities and the results are quite encouraging.

  7. Real-time prediction of earthquake ground motion: time evolutional prediction using data assimilation and real-time correction of site amplification factors

    Science.gov (United States)

    Hoshiba, M.

    2012-12-01

    In this presentation, I propose a new approach for real-time prediction of seismic ground motion which is applicable to Earthquake Early Waning (EEW). Many methods of EEW are based on a network method in which hypocenter and magnitude (source parameters) are quickly determined (that is, interpretation of current wavefield), and then the ground motions are predicted, and warnings are issued depending on the strength of the predicted ground motion. In this method, though we can predict ground motions using a few parameters (location of hypocenter, magnitude, site factors) at any points, it is necessary to determine the hypocenter and magnitude at first, and error of the source parameters leads directly to the error of the prediction. It is not easy to take the effects of rupture directivity and source extent into account, and it is impossible to fully reproduce the current wavefield from the interpreted source parameters. In general, wave motion is predictable when boundary condition and initial condition are given. Time evolutional prediction is a method based on this approach using the current wavefield as an initial condition, that is u(x, t+Δt)=H(u(x, t)), where u is the wave motion at location x at lapse time t, and H is the prediction operator. Future wave motion, u(x, t+Δt), is predicted from the distribution of the current wave motion u(x, t) using H. For H, finite difference technique or boundary integral equation method, such as Kirchhoff integral, is used. In the time evolutional prediction, determination of detailed distribution of current wave motion is a key, so that dense seismic observation network is required. Data assimilation is a technique to produce artificially denser network, which is widely used for numerical weather prediction and oceanography. Distribution of current wave motion is estimated from not only the current real observation of u(x, t), but also the prediction of one step before, H(u(x, t-Δt)). Combination of them produces denser

  8. Predicting Greater Prairie-Chicken Lek Site Suitability to Inform Conservation Actions.

    Directory of Open Access Journals (Sweden)

    Torre J Hovick

    Full Text Available The demands of a growing human population dictates that expansion of energy infrastructure, roads, and other development frequently takes place in native rangelands. Particularly, transmission lines and roads commonly divide rural landscapes and increase fragmentation. This has direct and indirect consequences on native wildlife that can be mitigated through thoughtful planning and proactive approaches to identifying areas of high conservation priority. We used nine years (2003-2011 of Greater Prairie-Chicken (Tympanuchus cupido lek locations totaling 870 unique leks sites in Kansas and seven geographic information system (GIS layers describing land cover, topography, and anthropogenic structures to model habitat suitability across the state. The models obtained had low omission rates (0.81, indicating high model performance and reliability of predicted habitat suitability for Greater Prairie-Chickens. We found that elevation was the most influential in predicting lek locations, contributing three times more predictive power than any other variable. However, models were improved by the addition of land cover and anthropogenic features (transmission lines, roads, and oil and gas structures. Overall, our analysis provides a hierarchal understanding of Greater Prairie-Chicken habitat suitability that is broadly based on geomorphological features followed by land cover suitability. We found that when land features and vegetation cover are suitable for Greater Prairie-Chickens, fragmentation by anthropogenic sources such as roadways and transmission lines are a concern. Therefore, it is our recommendation that future human development in Kansas avoid areas that our models identified as highly suitable for Greater Prairie-Chickens and focus development on land cover types that are of lower conservation concern.

  9. PreTIS: A Tool to Predict Non-canonical 5’ UTR Translational Initiation Sites in Human and Mouse

    Science.gov (United States)

    Reuter, Kerstin; Helms, Volkhard

    2016-01-01

    Translation of mRNA sequences into proteins typically starts at an AUG triplet. In rare cases, translation may also start at alternative non–AUG codons located in the annotated 5’ UTR which leads to an increased regulatory complexity. Since ribosome profiling detects translational start sites at the nucleotide level, the properties of these start sites can then be used for the statistical evaluation of functional open reading frames. We developed a linear regression approach to predict in–frame and out–of–frame translational start sites within the 5’ UTR from mRNA sequence information together with their translation initiation confidence. Predicted start codons comprise AUG as well as near–cognate codons. The underlying datasets are based on published translational start sites for human HEK293 and mouse embryonic stem cells that were derived by the original authors from ribosome profiling data. The average prediction accuracy of true vs. false start sites for HEK293 cells was 80%. When applied to mouse mRNA sequences, the same model predicted translation initiation sites observed in mouse ES cells with an accuracy of 76%. Moreover, we illustrate the effect of in silico mutations in the flanking sequence context of a start site on the predicted initiation confidence. Our new webservice PreTIS visualizes alternative start sites and their respective ORFs and predicts their ability to initiate translation. Solely, the mRNA sequence is required as input. PreTIS is accessible at http://service.bioinformatik.uni-saarland.de/pretis. PMID:27768687

  10. Residents’ Environmental Conservation Behaviors at Tourist Sites: Broadening the Norm Activation Framework by Adopting Environment Attachment

    Directory of Open Access Journals (Sweden)

    Yuling Zhang

    2016-06-01

    Full Text Available Understanding the factors that affect residents’ environmental conservation behaviors help in managing the environment of tourist sites. This research provides an integrative understanding of how residents near tourist sites form their environmental conservation behaviors by merging the norm-activation model and cognitive-affective model into one theoretical framework. Results of the structural analysis from a sample of 642 residents showed that this study’s proposed composite model includes a satisfactory level of predictive power for environmental conservation behaviors. The findings identify the following two dimensions of awareness of environmental consequences as having a key role in predicting environmental conservation behaviors: (1 awareness of positive consequences of environmental protection; and (2 awareness of disaster consequences. Results also show that environment attachment and personal norms about environmentalism played a mediating role between awareness of environmental consequences and environmental conservation behaviors, and that personal norms about environmentalism were the most powerful factor in predicting behaviors. Several practical implications were derived from the research findings that can contribute to environment management policy both within and outside the field of tourism, mostly notably: (1 how the effective promotion of these factors can encourage environmental conservation behaviors for residents; and (2 how governments can develop and implement environmental management measures to improve locals’ awareness of positive consequences of environmental protection.

  11. An epigenetic signature in peripheral blood predicts active ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Andrew E Teschendorff

    Full Text Available BACKGROUND: Recent studies have shown that DNA methylation (DNAm markers in peripheral blood may hold promise as diagnostic or early detection/risk markers for epithelial cancers. However, to date no study has evaluated the diagnostic and predictive potential of such markers in a large case control cohort and on a genome-wide basis. PRINCIPAL FINDINGS: By performing genome-wide DNAm profiling of a large ovarian cancer case control cohort, we here demonstrate that active ovarian cancer has a significant impact on the DNAm pattern in peripheral blood. Specifically, by measuring the methylation levels of over 27,000 CpGs in blood cells from 148 healthy individuals and 113 age-matched pre-treatment ovarian cancer cases, we derive a DNAm signature that can predict the presence of active ovarian cancer in blind test sets with an AUC of 0.8 (95% CI (0.74-0.87. We further validate our findings in another independent set of 122 post-treatment cases (AUC = 0.76 (0.72-0.81. In addition, we provide evidence for a significant number of candidate risk or early detection markers for ovarian cancer. Furthermore, by comparing the pattern of methylation with gene expression data from major blood cell types, we here demonstrate that age and cancer elicit common changes in the composition of peripheral blood, with a myeloid skewing that increases with age and which is further aggravated in the presence of ovarian cancer. Finally, we show that most cancer and age associated methylation variability is found at CpGs located outside of CpG islands. SIGNIFICANCE: Our results underscore the potential of DNAm profiling in peripheral blood as a tool for detection or risk-prediction of epithelial cancers, and warrants further in-depth and higher CpG coverage studies to further elucidate this role.

  12. Predictive Analysis of Landslide Activity Using Remote Sensing Data

    Science.gov (United States)

    Markuzon, N.; Regan, J.; Slesnick, C.

    2012-12-01

    Landslides are historically one of the most damaging geohazard phenomena in terms of death tolls and socio-economic losses. Therefore, understanding the underlying causes of landslides and how environmental phenomena affect their frequency and severity is of critical importance. Of specific importance for mitigating future damage is increasing our understanding of how climate change will affect landslide severity, occurrence rates, and damage. We are developing data driven models aimed at predicting landslide activity. The models learn multi-dimensional weather and geophysical patterns associated with historical landslides and estimate location-dependent probabilities for landslides under current or future weather and geophysical conditions. Our approach uses machine learning algorithms capable of determining non-linear associations between dependent variables and landslide occurrence without requiring detailed knowledge of geomorphology. Our primary goal in year one of the project is to evaluate the predictive capabilities of data mining models in application to landslide activity, and to analyze if the approach will discover previously unknown variables and/or relationships important to landslide occurrence, frequency or severity. The models include remote sensing and ground-based data, including weather, landcover, slope, elevation and drainage information as well as urbanization data. The historical landslide dataset we used to build our preliminary models was compiled from City of Seattle landslide files, United States Geological Survey reports, newspaper articles, and a verified subset of the Seattle Landslide Database that consists of all reported landslides within Seattle, WA, between 1948 and 1999. Most of the landslides analyzed to-date are shallow. Using statistical analysis and unsupervised clustering methods we have thus far identified subsets of weather conditions that lead to a significantly higher landslide probability, and have developed

  13. Screening breeding sites of the common toad (Bufo bufo) in England and Wales for evidence of endocrine disrupting activity.

    Science.gov (United States)

    Pickford, Daniel B; Jones, Alexandra; Velez-Pelez, Alejandra; Orton, Frances; Iguchi, Taisen; Mitsui, Naoko; Tooi, Osamu

    2015-07-01

    Anuran amphibians are often present in agricultural landscapes and may therefore be exposed to chemicals in surface waters used for breeding. We used passive accumulation devices (SPMD and POCIS) to sample contaminants from nine breeding sites of the Common toad (Bufo bufo) across England and Wales, measuring endocrine activity of the extracts in a recombinant yeast androgen screen (YAS) and yeast estrogen screen (YES) and an in vitro vitellogenin induction screen in primary culture of Xenopus laevis hepatocytes. We also assessed hatching, growth, survival, and development in caged larvae in situ, and sampled metamorphs for gonadal histopathology. None of the SPMD extracts exhibited estrogen receptor or androgen receptor agonist activity, while POCIS extracts from two sites in west-central England exhibited concentration-dependent androgenic activity in the YAS. Three sites exhibited significant estrogenic activity in both the YES and the Xenopus hepatocyte. Hatching rates varied widely among sites, but there was no consistent correlation between hatching rate and intensity of agricultural activity, predicted concentrations of agrochemicals, or endocrine activity measured in YES/YAS assays. While a small number of intersex individuals were observed, their incidence could not be associated with predicted pesticide exposure or endocrine activitity measured in the in vitro screens. There were no significant differences in sex ratio, as determined by gonadal histomorphology among the study sites, and no significant correlation was observed between proportion of males and predicted exposure to agrochemicals. However, a negative correlation did become apparent in later sampling periods between proportion of males and estrogenic activity of the POCIS sample, as measured in the YES. Our results suggest that larval and adult amphibians may be exposed to endocrine disrupting chemicals in breeding ponds, albeit at low concentrations, and that chemical contaminants other than

  14. Ngram time series model to predict activity type and energy cost from wrist, hip and ankle accelerometers: implications of age.

    Science.gov (United States)

    Strath, Scott J; Kate, Rohit J; Keenan, Kevin G; Welch, Whitney A; Swartz, Ann M

    2015-11-01

    To develop and test time series single site and multi-site placement models, we used wrist, hip and ankle processed accelerometer data to estimate energy cost and type of physical activity in adults. Ninety-nine subjects in three age groups (18-39, 40-64, 65 +  years) performed 11 activities while wearing three triaxial accelereometers: one each on the non-dominant wrist, hip, and ankle. During each activity net oxygen cost (METs) was assessed. The time series of accelerometer signals were represented in terms of uniformly discretized values called bins. Support Vector Machine was used for activity classification with bins and every pair of bins used as features. Bagged decision tree regression was used for net metabolic cost prediction. To evaluate model performance we employed the jackknife leave-one-out cross validation method. Single accelerometer and multi-accelerometer site model estimates across and within age group revealed similar accuracy, with a bias range of -0.03 to 0.01 METs, bias percent of -0.8 to 0.3%, and a rMSE range of 0.81-1.04 METs. Multi-site accelerometer location models improved activity type classification over single site location models from a low of 69.3% to a maximum of 92.8% accuracy. For each accelerometer site location model, or combined site location model, percent accuracy classification decreased as a function of age group, or when young age groups models were generalized to older age groups. Specific age group models on average performed better than when all age groups were combined. A time series computation show promising results for predicting energy cost and activity type. Differences in prediction across age group, a lack of generalizability across age groups, and that age group specific models perform better than when all ages are combined needs to be considered as analytic calibration procedures to detect energy cost and type are further developed. PMID:26449155

  15. Management of Ground and Groundwater Contamination on a Compact Site Constrained by Ongoing Activities

    International Nuclear Information System (INIS)

    the design of a new characterisation project has had to be constantly reworked to ensure fragile plants, site services, current operations and decommissioning projects are not impacted. 2. Assessment of Risk to the public and workforce. Risks need to be assessed for the short, medium and long term. The main pathways to receptors are through groundwater or excavations. Risks to the public are complicated through the proximity of the site to major receptors such as the sea and a near-by farm. As entry to the site is controlled, excavations into contaminated ground are only possible by members of the workforce whose activities are managed to minimise any risk. This is through a system of excavation permits and authorisations for disposal of excavated material which can add significant time and cost to construction projects on site. 3. Prioritisation of remediation. Large volumes of impacted ground and groundwater sit beneath fragile buildings with significant inventories. With current decommissioning schedules whole-scale remediation of ground and groundwater near or under key buildings cannot commence for at least another 40 plus years. Early remediation and/or containment of groundwater further away from the source terms and remediation of smaller accessible areas of contamination are being considered and will be assessed through a comprehensive optioneering process. Long term clean-up strategies run into the early part of the 22. Century, making any predictions as to the end-use of the site and therefore clean-up criteria for current projects difficult to determine. Management of information and data is key in establishing this strategy and information relevant to contaminated land has been collected in various forms over the 60 year history of the site. This data and information is currently being pulled together by the Land Quality team where it can be put into a form that can be easily assessed, visualised and modelled as well as being managed and stored for future

  16. From stiffness to strength in site response predictions: Formulation and validation of a hybrid hyperbolic nonlinear soil model

    Science.gov (United States)

    Asimaki, D.; Shi, J.

    2015-12-01

    Nonlinear site response analyses are becoming an increasingly important component of simulated ground motions intended for engineering applications. For regional-scale problems where geotechnical data are sparse, the challenge lies in computing nonlinear ground deformation to very strong ground shaking using a very small number of input parameters. We have developed a nonlinear model that addresses these issues: it simultaneously captures the soil's low-strain stiffness and large-strain strength of soil, and yields reliable predictions of soil response to weak and strong shaking using as sole input the shear wave velocity profile. We here present the formulation of the model and an extensive validation study based on downhole array recordings, with peak ground acceleration ranging from 0.01-0.9g. We also show that our model, referred to as hybrid hyperbolic, outperforms existing nonlinear formulations and simplified site response analyses widely used in practice for ground motions that induce more than 0.02% of soil strain (roughly equivalent to PGA higher than 0.02g). In addition to site-specific response predictions at sites with limited site characterization, the hybrid-hyperbolic model can help improve site amplification factors of ground motion prediction equations (GMPEs) by complementing the empirical data with simulated site response analyses for very strong ground shaking; as well as physics-based ground motion simulations, particularly for deeper sedimentary sites with low resonant frequencies.

  17. 10 CFR 60.18 - Review of site characterization activities. 2

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Review of site characterization activities. 2 60.18... IN GEOLOGIC REPOSITORIES Licenses Preapplication Review § 60.18 Review of site characterization activities. 2 2 In addition to the review of site characterization activities specified in this section,...

  18. Hazardous Material Storage Facilities and Sites - WASTE_SOLID_ACTIVE_PERMITTED_IDEM_IN: Active Permitted Solid Waste Sites in Indiana (Indiana Department of Environmental Management, Point Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — WASTE_SOLID_ACTIVE_PERMITTED_IDEM_IN is a point shapefile that contains active permitted solid waste site locations in Indiana, provided by personnel of Indiana...

  19. Structure prediction and activity analysis of human heme oxygenase-1 and its mutant

    Institute of Scientific and Technical Information of China (English)

    Zhen-Wei Xia; Wen-Pu Zhou; Wen-Jun Cui; Xue-Hong Zhang; Qing-Xiang Shen; Yun-Zhu Li; Shan-Chang Yu

    2004-01-01

    AIM: To predict wild human heme oxygenase-1 (whHO-1)and hHO-1 His25Ala mutant (△hHO-1) structures, to clone and express them and analyze their activities.METHODS: Swiss-PdbViewer and Antheprot 5.0 were used for the prediction of structure diversity and physicalchemical changes between wild and mutant hHO-1. hHO1 His25Ala mutant cDNA was constructed by site-directed mutagenesis in two plasmids of E. coli DH5α. Expression products were purified by ammonium sulphate precipitation and Q-Sepharose Fast Flow column chromatography, and their activities were measured.RESULTS: rHO-1 had the structure of a helical fold with the heme sandwiched between heme-heme oxygenase1 helices. Bond angle, dihedral angle and chemical bond in the active pocket changed after Ala25 was replaced by His25, but Ala25 was still contacting the surface and the electrostatic potential of the active pocket was negative. The mutated enzyme kept binding activity to heme. Two vectors pBHO-1 and pBHO-1(M) were constructed and expressed. Ammonium sulphate precipitation and column chromatography yielded 3.6-fold and 30-fold higher purities of whHO-1, respectively. The activity of △hHO-1 was reduced 91.21% after mutation compared with whHO-1.CONCLUSION: Proximal His25 ligand is crucial for normal hHO-1 catalytic activity. △hHO-1 is deactivated by mutation but keeps the same binding site as whHO-1. △hHO-1 might be a potential inhibitor of whHO-1 for preventing neonatal hyperbilirubinemia.

  20. Active site conformational dynamics in human uridine phosphorylase 1.

    Directory of Open Access Journals (Sweden)

    Tarmo P Roosild

    Full Text Available Uridine phosphorylase (UPP is a central enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate. Human UPP activity has been a focus of cancer research due to its role in activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5-fluorouracil (5-FU and capecitabine. Additionally, specific molecular inhibitors of this enzyme have been found to raise endogenous uridine concentrations, which can produce a cytoprotective effect on normal tissues exposed to these drugs. Here we report the structure of hUPP1 bound to 5-FU at 2.3 A resolution. Analysis of this structure reveals new insights as to the conformational motions the enzyme undergoes in the course of substrate binding and catalysis. The dimeric enzyme is capable of a large hinge motion between its two domains, facilitating ligand exchange and explaining observed cooperativity between the two active sites in binding phosphate-bearing substrates. Further, a loop toward the back end of the uracil binding pocket is shown to flexibly adjust to the varying chemistry of different compounds through an "induced-fit" association mechanism that was not observed in earlier hUPP1 structures. The details surrounding these dynamic aspects of hUPP1 structure and function provide unexplored avenues to develop novel inhibitors of this protein with improved specificity and increased affinity. Given the recent emergence of new roles for uridine as a neuron protective compound in ischemia and degenerative diseases, such as Alzheimer's and Parkinson's, inhibitors of hUPP1 with greater efficacy, which are able to boost cellular uridine levels without adverse side-effects, may have a wide range of therapeutic applications.

  1. Prediction of protein modification sites of pyrrolidone carboxylic acid using mRMR feature selection and analysis.

    Directory of Open Access Journals (Sweden)

    Lu-Lu Zheng

    Full Text Available Pyrrolidone carboxylic acid (PCA is formed during a common post-translational modification (PTM of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR and incremental feature selection (IFS. We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations.

  2. Recent and Past Musical Activity Predicts Cognitive Aging Variability: Direct Comparison with Leisure Activities

    Directory of Open Access Journals (Sweden)

    Brenda eHanna-Pladdy

    2012-07-01

    Full Text Available Studies evaluating the impact of modifiable lifestyle factors on cognition offer potential insights into sources of cognitive aging variability. Recently, we reported an association between extent of musical instrumental practice throughout the life span (greater than 10 years on preserved cognitive functioning in advanced age . These findings raise the question of whether there are training-induced brain changes in musicians that can transfer to nonmusical cognitive abilities to allow for compensation of age-related cognitive declines. However, because of the relationship between engagement in lifestyle activities and preserved cognition, it remains unclear whether these findings are specifically driven by musical training or the types of individuals likely to engage in greater activities in general. The current study examined the type of leisure activity (musical versus other as well as the timing of engagement (age of acquisition, past versus recent in predictive models of successful cognitive aging. Seventy age and education matched older musicians (> 10 years and nonmusicians (ages 59-80 were evaluated on neuropsychological tests and life-style activities (AAP. Partition analyses were conducted on significant cognitive measures to explain performance variance in musicians. Musicians scored higher on tests of phonemic fluency, verbal immediate recall, judgment of line orientation (JLO, and Letter Number Sequencing (LNS, but not the AAP. The first partition analysis revealed education best predicted JLO in musicians, followed by recent musical engagement which offset low education. In the second partition analysis, early age of musical acquisition (< 9 years predicted enhanced LNS in musicians, while analyses for AAP, verbal recall and fluency were not predictive. Recent and past musical activity, but not leisure activity, predicted variability across verbal and visuospatial domains in aging. Early musical acquisition predicted auditory

  3. Predicted impacts of future water level decline on monitoring wells using a ground-water model of the Hanford Site

    International Nuclear Information System (INIS)

    A ground-water flow model was used to predict water level decline in selected wells in the operating areas (100, 200, 300, and 400 Areas) and the 600 Area. To predict future water levels, the unconfined aquifer system was stimulated with the two-dimensional version of a ground-water model of the Hanford Site, which is based on the Coupled Fluid, Energy, and Solute Transport (CFEST) Code in conjunction with the Geographic Information Systems (GIS) software package. The model was developed using the assumption that artificial recharge to the unconfined aquifer system from Site operations was much greater than any natural recharge from precipitation or from the basalt aquifers below. However, artificial recharge is presently decreasing and projected to decrease even more in the future. Wells currently used for monitoring at the Hanford Site are beginning to go dry or are difficult to sample, and as the water table declines over the next 5 to 10 years, a larger number of wells is expected to be impacted. The water levels predicted by the ground-water model were compared with monitoring well completion intervals to determine which wells will become dry in the future. Predictions of wells that will go dry within the next 5 years have less uncertainty than predictions for wells that will become dry within 5 to 10 years. Each prediction is an estimate based on assumed future Hanford Site operating conditions and model assumptions

  4. Decreased dopamine activity predicts relapse in methamphetamine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  5. Measured and predicted aerosol light scattering enhancement factors at the high alpine site Jungfraujoch

    Directory of Open Access Journals (Sweden)

    R. Fierz-Schmidhauser

    2009-09-01

    Full Text Available Ambient relative humidity (RH determines the water content of atmospheric aerosol particles and thus has an important influence on the amount of visible light scattered by particles. The RH dependence of the particle light scattering coefficient (σsp is therefore an important variable for climate forcing calculations. We used a humidification system for a nephelometer which allows for the measurement of σsp at a defined RH in the range of 20–95%. In this paper we present measurements of light scattering enhancement factors f(RH=σsp(RH/σsp(dry from a 1-month campaign (May 2008 at the high alpine site Jungfraujoch (3580 m a.s.l., Switzerland. At this site, f(RH=85% varied between 1.2 and 3.3. Measured f(RH agreed well with f(RH calculated with Mie theory using measurements of the size distribution, chemical composition and hygroscopic diameter growth factors as input. Good f(RH predictions at RH<85% were also obtained with a simplified model, which uses the Ångström exponent of σsp(dry as input. RH influences further intensive optical aerosol properties. The backscatter fraction decreased by about 30% from 0.128 to 0.089, and the single scattering albedo increased on average by 0.05 at 85% RH compared to dry conditions. These changes in σsp, backscatter fraction and single scattering albedo have a distinct impact on the radiative forcing of the Jungfraujoch aerosol.

  6. Measured and predicted aerosol light scattering enhancement factors at the high alpine site Jungfraujoch

    Directory of Open Access Journals (Sweden)

    R. Fierz-Schmidhauser

    2010-03-01

    Full Text Available Ambient relative humidity (RH determines the water content of atmospheric aerosol particles and thus has an important influence on the amount of visible light scattered by particles. The RH dependence of the particle light scattering coefficient (σsp is therefore an important variable for climate forcing calculations. We used a humidification system for a nephelometer which allows for the measurement of σsp at a defined RH in the range of 20–95%. In this paper we present measurements of light scattering enhancement factors f(RH=σsp(RH/σsp(dry from a 1-month campaign (May 2008 at the high alpine site Jungfraujoch (3580 m a.s.l., Switzerland. Measurements at the Jungfraujoch are representative for the lower free troposphere above Central Europe. For this aerosol type hardly any information about the f(RH is available so far. At this site, f(RH=85% varied between 1.2 and 3.3. Measured f(RH agreed well with f(RH calculated with Mie theory using measurements of the size distribution, chemical composition and hygroscopic diameter growth factors as input. Good f(RH predictions at RH<85% were also obtained with a simplified model, which uses the Ångström exponent of σsp(dry as input. RH influences further intensive optical aerosol properties. The backscatter fraction decreased by about 30% from 0.128 to 0.089, and the single scattering albedo increased on average by 0.05 at 85% RH compared to dry conditions. These changes in σsp, backscatter fraction and single scattering albedo have a distinct impact on the radiative forcing of the Jungfraujoch aerosol.

  7. Solubility Prediction of Active Pharmaceutical Compounds with the UNIFAC Model

    Science.gov (United States)

    Nouar, Abderrahim; Benmessaoud, Ibtissem; Koutchoukali, Ouahiba; Koutchoukali, Mohamed Salah

    2016-03-01

    The crystallization from solution of an active pharmaceutical ingredient requires the knowledge of the solubility in the entire temperature range investigated during the process. However, during the development of a new active ingredient, these data are missing. Its experimental determination is possible, but tedious. UNIFAC Group contribution method Fredenslund et al. (Vapor-liquid equilibria using UNIFAC: a group contribution method, 1977; AIChE J 21:1086, 1975) can be used to predict this physical property. Several modifications on this model have been proposed since its development in 1977, modified UNIFAC of Dortmund Weidlich et al. (Ind Eng Chem Res 26:1372, 1987), Gmehling et al. (Ind Eng Chem Res 32:178, 1993), Pharma-modified UNIFAC Diedrichs et al. (Evaluation und Erweiterung thermodynamischer Modelle zur Vorhersage von Wirkstofflöslichkeiten, PhD Thesis, 2010), KT-UNIFAC Kang et al. (Ind Eng Chem Res 41:3260, 2002), ldots In this study, we used UNIFAC model by considering the linear temperature dependence of interaction parameters as in Pharma-modified UNIFAC and structural groups as defined by KT-UNIFAC first-order model. More than 100 binary datasets were involved in the estimation of interaction parameters. These new parameters were then used to calculate activity coefficient and solubility of some molecules in various solvents at different temperatures. The model gives better results than those from the original UNIFAC and shows good agreement between the experimental solubility and the calculated one.

  8. Autonomic activity during sleep predicts memory consolidation in humans.

    Science.gov (United States)

    Whitehurst, Lauren N; Cellini, Nicola; McDevitt, Elizabeth A; Duggan, Katherine A; Mednick, Sara C

    2016-06-28

    Throughout history, psychologists and philosophers have proposed that good sleep benefits memory, yet current studies focusing on the relationship between traditionally reported sleep features (e.g., minutes in sleep stages) and changes in memory performance show contradictory findings. This discrepancy suggests that there are events occurring during sleep that have not yet been considered. The autonomic nervous system (ANS) shows strong variation across sleep stages. Also, increases in ANS activity during waking, as measured by heart rate variability (HRV), have been correlated with memory improvement. However, the role of ANS in sleep-dependent memory consolidation has never been examined. Here, we examined whether changes in cardiac ANS activity (HRV) during a daytime nap were related to performance on two memory conditions (Primed and Repeated) and a nonmemory control condition on the Remote Associates Test. In line with prior studies, we found sleep-dependent improvement in the Primed condition compared with the Quiet Wake control condition. Using regression analyses, we compared the proportion of variance in performance associated with traditionally reported sleep features (model 1) vs. sleep features and HRV during sleep (model 2). For both the Primed and Repeated conditions, model 2 (sleep + HRV) predicted performance significantly better (73% and 58% of variance explained, respectively) compared with model 1 (sleep only, 46% and 26% of variance explained, respectively). These findings present the first evidence, to our knowledge, that ANS activity may be one potential mechanism driving sleep-dependent plasticity. PMID:27298366

  9. Detection limit for activation measurements in ultralow background sites

    Science.gov (United States)

    Trache, Livius; Chesneanu, D.; Margineanu, R.; Pantelica, A.; Ghita, D. G.; Burducea, I.; Straticiuc, M.; Tang, X. D.

    2014-09-01

    We used 12C +13C fusion at the beam energies E = 6, 7 and 8 MeV to determine the sensitivity and the limits of activation method measurements in ultralow background sites. A 13C beam of 0.5 μA from the 3 MV Tandem accelerator of the Horia Hulubei National Institute of Physics and Nuclear Engineering - IFIN HH impinged on thick graphite targets. After about 24 hrs of irradiation targets were measured in two different laboratories: one with a heavy shielded Ge detector in the institute (at the surface) and one located underground in the microBequerel laboratory, in the salt mine of Slanic-Prahova, Romania. The 1369- and 2754 keV peaks from 24Na deactivation were clearly observed in the γ-ray spectra obtained for acquisitions lasting a few hours, or a few days. Determination of the detection limit in evaluating the cross sections for the target irradiated at Ec . m = 3 MeV indicates the fact that it is possible to measure gamma spectrum in underground laboratory down to Ec . m = 2 . 6 MeV. Cleaning the spectra with beta-gamma coincidences and increasing beam intensity 20 times will take as further down. The measurements are motivated by the study of the 12 C +12 C reaction at astrophysical energies.

  10. Sequence-specific flexibility organization of splicing flanking sequence and prediction of splice sites in the human genome.

    Science.gov (United States)

    Zuo, Yongchun; Zhang, Pengfei; Liu, Li; Li, Tao; Peng, Yong; Li, Guangpeng; Li, Qianzhong

    2014-09-01

    More and more reported results of nucleosome positioning and histone modifications showed that DNA structure play a well-established role in splicing. In this study, a set of DNA geometric flexibility parameters originated from molecular dynamics (MD) simulations were introduced to discuss the structure organization around splice sites at the DNA level. The obtained profiles of specific flexibility/stiffness around splice sites indicated that the DNA physical-geometry deformation could be used as an alternative way to describe the splicing junction region. In combination with structural flexibility as discriminatory parameter, we developed a hybrid computational model for predicting potential splicing sites. And the better prediction performance was achieved when the benchmark dataset evaluated. Our results showed that the mechanical deformability character of a splice junction is closely correlated with both the splice site strength and structural information in its flanking sequences.

  11. Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran.

    Science.gov (United States)

    Honarmand-Jahromy, Sahar; Siavoshi, Farideh; Malekzadeh, Reza; Sattari, Taher Nejad; Latifi-Navid, Saeid

    2015-12-01

    Biological activity of Helicobacter pylori oncoprotein CagA is determined by a diversity in the tyrosine phosphorylation motif sites. In the present study, the diversity and the type of the H. pylori CagA EPIYA motifs and their association with gastric ulcer (GU) and duodenal ulcer (DU) in Iranian dyspeptic patients were assessed. PCR amplification, sequencing, and bioinformatic analysis were performed to determine the pattern of CagA EPIYA motifs. Of 168 H. pylori cagA(+) strains, the frequency of ABC was 93.50%, ABCCC 5.40%, ABC + ABCCC 0.6% and ABCC 0.6%. There was no EPIYA-D segment. The ABCCC pattern of EPIYA motif was more frequent in the H. pylori isolates from GU (8/50, 16%) than in those from chronic gastritis (CG) (0/81, 0%) (P = 0). In contrast, The ABC pattern of EPIYA motif was less frequent in the H. pylori isolates from GU (41/50, 82%) than in those from CG (80/81, 98.80%) (Age-sex-adjusted odds ratio (OR) = 0.020, 95% CI = 0.002-0.259; P = 0.003). The distribution of the ABC motif was almost the same in H. pylori isolates from CG (98.80%) and DU diseases (97.30%). There was no significant association between the number of CagA EPIYA-C segment and DU (P > 0.05). We have proposed that CagA from Iranian H. pylori strains were Western type and all strains had active phosphorylation sites. The three EPIYA-C motifs of CagA were more frequently observed in the H. pylori strains from GU; thus it might be an important biomarker for predicting the GU risk in Iran.

  12. Predicting eruptions from precursory activity using remote sensing data hybridization

    Science.gov (United States)

    Reath, K. A.; Ramsey, M. S.; Dehn, J.; Webley, P. W.

    2016-07-01

    Many volcanoes produce some level of precursory activity prior to an eruption. This activity may or may not be detected depending on the available monitoring technology. In certain cases, precursors such as thermal output can be interpreted to make forecasts about the time and magnitude of the impending eruption. Kamchatka (Russia) provides an ideal natural laboratory to study a wide variety of eruption styles and precursory activity prior to an eruption. At Bezymianny volcano for example, a clear increase in thermal activity commonly occurs before an eruption, which has allowed predictions to be made months ahead of time. Conversely, the eruption of Tolbachik volcano in 2012 produced no discernable thermal precursors before the large scale effusive eruption. However, most volcanoes fall between the extremes of consistently behaved and completely undetectable, which is the case with neighboring Kliuchevskoi volcano. This study tests the effectiveness of using thermal infrared (TIR) remote sensing to track volcanic thermal precursors using data from both the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Advanced Very High Resolution Radiometer (AVHRR) sensors. It focuses on three large eruptions that produced different levels and durations of effusive and explosive behavior at Kliuchevskoi. Before each of these eruptions, TIR spaceborne sensors detected thermal anomalies (i.e., pixels with brightness temperatures > 2 °C above the background temperature). High-temporal, low-spatial resolution (i.e., ~ hours and 1 km) AVHRR data are ideal for detecting large thermal events occurring over shorter time scales, such as the hot material ejected following strombolian eruptions. In contrast, high-spatial, low-temporal resolution (i.e., days to weeks and 90 m) ASTER data enables the detection of much lower thermal activity; however, activity with a shorter duration will commonly be missed. ASTER and AVHRR data are combined to track low

  13. Predicting transcription factor binding sites using local over-representation and comparative genomics

    Directory of Open Access Journals (Sweden)

    Touzet Hélène

    2006-08-01

    Full Text Available Abstract Background Identifying cis-regulatory elements is crucial to understanding gene expression, which highlights the importance of the computational detection of overrepresented transcription factor binding sites (TFBSs in coexpressed or coregulated genes. However, this is a challenging problem, especially when considering higher eukaryotic organisms. Results We have developed a method, named TFM-Explorer, that searches for locally overrepresented TFBSs in a set of coregulated genes, which are modeled by profiles provided by a database of position weight matrices. The novelty of the method is that it takes advantage of spatial conservation in the sequence and supports multiple species. The efficiency of the underlying algorithm and its robustness to noise allow weak regulatory signals to be detected in large heterogeneous data sets. Conclusion TFM-Explorer provides an efficient way to predict TFBS overrepresentation in related sequences. Promising results were obtained in a variety of examples in human, mouse, and rat genomes. The software is publicly available at http://bioinfo.lifl.fr/TFM-Explorer.

  14. A new method for splice site prediction based on the sequence patterns of splicing signals and regulatory elements

    Institute of Scientific and Technical Information of China (English)

    SUN ZongXiao; SANG LingJie; JU LiNing; ZHU HuaiQiu

    2008-01-01

    It is of significance for splice site prediction to develop novel algorithms that combine the sequence patterns of regulatory elements such as enhancers and silencers with the patterns of splicing signals. In this paper, a statistical model of splicing signals was built based on the entropy density profile (EDP) method, weight array method (WAM) and κ test; moreover, the model of splicing regulatory elements was developed by an unsupervised self-learning method to detect motifs associated with regulatory elements. With two models incorporated, a multi-level support vector machine (SVM) system was de-vised to perform ab initio prediction for splice sites originating from DNA sequence in eukaryotic ge-home. Results of large scale tests on human genomic splice sites show that the new method achieves a comparative high performance in splice site prediction. The method is demonstrated to be with at least the same level of performance and usually better performance than the existing SpliceScan method based on modeling regulatory elements, and shown to have higher accuracies than the traditional methods with modeling splicing signals such as the GeneSplicer. In particular, the method has evident advantage over splice site prediction for the genes with lower GC content.

  15. Brain monoamine oxidase A activity predicts trait aggression.

    Science.gov (United States)

    Alia-Klein, Nelly; Goldstein, Rita Z; Kriplani, Aarti; Logan, Jean; Tomasi, Dardo; Williams, Benjamin; Telang, Frank; Shumay, Elena; Biegon, Anat; Craig, Ian W; Henn, Fritz; Wang, Gene-Jack; Volkow, Nora D; Fowler, Joanna S

    2008-05-01

    The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression. PMID:18463263

  16. Monoclonal antibody against the active site of caeruloplasmin and the ELISA system detecting active caeruloplasmin.

    Science.gov (United States)

    Hiyamuta, S; Ito, K

    1994-04-01

    Serum caeruloplasmin deficiency is a characteristic biochemical abnormality found in patients with Wilson's disease, but the mechanism of this disease is unknown. Although the phenylenediamine oxidase activity of serum caeruloplasmin is markedly low in patients with Wilson's disease, mRNA of caeruloplasmin exists to some extent. To investigate the deficiency of caeruloplasmin oxidase activity in Wilson's disease, we generated 14 monoclonal antibodies (MAbs) and selected ID1, which had the strongest reactivity, and ID2, which had neutralizing ability. We also established a system to measure active caeruloplasmin specifically using these MAbs. These MAbs and the system will be useful tools in analyzing the active site of caeruloplasmin in patients with Wilson's disease.

  17. Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites

    Science.gov (United States)

    Vukovic, Sinisa; Brennan, Paul E.; Huggins, David J.

    2016-09-01

    The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

  18. Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites.

    Science.gov (United States)

    Vukovic, Sinisa; Brennan, Paul E; Huggins, David J

    2016-09-01

    The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process. PMID:27367338

  19. Robotics and Automation Activities at the Savannah River Site: A Site Report for SUBWOG 39F

    International Nuclear Information System (INIS)

    The Savannah River Site has successfully used robots, teleoperators, and remote video to reduce exposure to ionizing radiation, improve worker safety, and improve the quality of operations. Previous reports have described the use of mobile teleoperators in coping with a high level liquid waste spill, the removal of highly contaminated equipment, and the inspection of nuclear reactor vessels. This report will cover recent applications at the Savannah River, as well as systems which SRS has delivered to other DOE site customers

  20. A novel method for protein-protein interaction site prediction using phylogenetic substitution models

    OpenAIRE

    La, David; Kihara, Daisuke

    2011-01-01

    Protein-protein binding events mediate many critical biological functions in the cell. Typically, functionally important sites in proteins can be well identified by considering sequence conservation. However, protein-protein interaction sites exhibit higher sequence variation than other functional regions, such as catalytic sites of enzymes. Consequently, the mutational behavior leading to weak sequence conservation poses significant challenges to the protein-protein interaction site predicti...

  1. A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren;

    1997-01-01

    We have developed a new method for the identication of signal peptides and their cleavage sites based on neural networks trained on separate sets of prokaryotic and eukaryotic sequences. The method performs signicantly better than previous prediction schemes, and can easily be applied to genome...

  2. Neural network model for the prediction of PM10 daily concentrations in two sites in the Western Mediterranean.

    Science.gov (United States)

    de Gennaro, Gianluigi; Trizio, Livia; Di Gilio, Alessia; Pey, Jorge; Pérez, Noemi; Cusack, Michael; Alastuey, Andrés; Querol, Xavier

    2013-10-01

    An artificial neural network (ANN) was developed and tested to forecast PM10 daily concentration in two contrasted environments in NE Spain, a regional background site (Montseny), and an urban background site (Barcelona-CSIC), which was highly influenced by vehicular emissions. In order to predict 24-h average PM10 concentrations, the artificial neural network previously developed by Caselli et al. (2009) was improved by using hourly PM concentrations and deterministic factors such as a Saharan dust alert. In particular, the model input data for prediction were the hourly PM10 concentrations 1-day in advance, local meteorological data and information about air masses origin. The forecasted performance indexes for both sites were calculated and they showed better results for the regional background site in Montseny (R(2)=0.86, SI=0.75) than for urban site in Barcelona (R(2)=0.73, SI=0.58), influenced by local and sometimes unexpected sources. Moreover, a sensitivity analysis conducted to understand the importance of the different variables included among the input data, showed that local meteorology and air masses origin are key factors in the model forecasts. This result explains the reason for the improvement of ANN's forecasting performance at the Montseny site with respect to the Barcelona site. Moreover, the artificial neural network developed in this work could prove useful to predict PM10 concentrations, especially, at regional background sites such as those on the Mediterranean Basin which are primarily affected by long-range transports. Hence, the artificial neural network presented here could be a powerful tool for obtaining real time information on air quality status and could aid stakeholders in their development of cost-effective control strategies.

  3. Predicting pupylation sites in prokaryotic proteins using semi-supervised self-training support vector machine algorithm.

    Science.gov (United States)

    Ju, Zhe; Gu, Hong

    2016-08-15

    As one important post-translational modification of prokaryotic proteins, pupylation plays a key role in regulating various biological processes. The accurate identification of pupylation sites is crucial for understanding the underlying mechanisms of pupylation. Although several computational methods have been developed for the identification of pupylation sites, the prediction accuracy of them is still unsatisfactory. Here, a novel bioinformatics tool named IMP-PUP is proposed to improve the prediction of pupylation sites. IMP-PUP is constructed on the composition of k-spaced amino acid pairs and trained with a modified semi-supervised self-training support vector machine (SVM) algorithm. The proposed algorithm iteratively trains a series of support vector machine classifiers on both annotated and non-annotated pupylated proteins. Computational results show that IMP-PUP achieves the area under receiver operating characteristic curves of 0.91, 0.73, and 0.75 on our training set, Tung's testing set, and our testing set, respectively, which are better than those of the different error costs SVM algorithm and the original self-training SVM algorithm. Independent tests also show that IMP-PUP significantly outperforms three other existing pupylation site predictors: GPS-PUP, iPUP, and pbPUP. Therefore, IMP-PUP can be a useful tool for accurate prediction of pupylation sites. A MATLAB software package for IMP-PUP is available at https://juzhe1120.github.io/. PMID:27197054

  4. Prediction of protein binding sites using physical and chemical descriptors and the support vector machine regression method

    Institute of Scientific and Technical Information of China (English)

    Sun Zhong-Hua; Jiang Fan

    2010-01-01

    In this paper a new continuous variable called core-ratio is defined to describe the probability for a residue to be in a binding site, thereby replacing the previous binary description of the interface residue using 0 and 1. So we can use the support vector machine regression method to fit the core-ratio value and predict the protein binding sites. We also design a new group of physical and chemical descriptors to characterize the binding sites. The new descriptors are more effective, with an averaging procedure used. Our test shows that much better prediction results can be obtained by the support vector regression (SVR) method than by the support vector classification method.

  5. The active sites of supported silver particle catalysts in formaldehyde oxidation.

    Science.gov (United States)

    Chen, Yaxin; Huang, Zhiwei; Zhou, Meijuan; Hu, Pingping; Du, Chengtian; Kong, Lingdong; Chen, Jianmin; Tang, Xingfu

    2016-08-01

    Surface silver atoms with upshifted d-orbitals are identified as the catalytically active sites in formaldehyde oxidation by correlating their activity with the number of surface silver atoms, and the degree of the d-orbital upshift governs the catalytic performance of the active sites. PMID:27406403

  6. Mapping the ribonucleolytic active site of bovine seminal ribonuclease. The binding of pyrimidinyl phosphonucleotide inhibitors.

    Science.gov (United States)

    Dossi, Kyriaki; Tsirkone, Vicky G; Hayes, Joseph M; Matousek, Josef; Poucková, Pavla; Soucek, Josef; Zadinova, Marie; Zographos, Spyros E; Leonidas, Demetres D

    2009-11-01

    Bovine seminal ribonuclease (BS-RNase) is a 27kDa homodimeric enzyme and a member of the pancreatic RNase A superfamily. It is the only RNase with a quaternary structure and it is a mixture of two dimeric forms. In the most abundant form the active site is formed by the swapping of the N-terminal segments. BS-RNase is a potent antitumor agent with severe side effects such as aspermatogenicity, and immunosuppression. As a first step towards the design of potent inhibitors of this enzyme we mapped its active site through the study of the binding of uridine 2'-phosphate (U2'p), uridine 3'-phosphate (U3'p), uridine 5'-diphosphate (UDP), cytidine 3'-phosphate (C3'p), and cytidine 5-phosphate (C5'p), by kinetics, and X-ray crystallography. These phosphonucleotides are potent inhibitors with C3'p being the most potent with a K(i) value of 22 microM. Absorption, distribution, metabolism, and excretion pharmacokinetic property predictions reveal U2'p, U3'p, and C5'p as the most promising with respect to oral bioavailability. In vivo studies on the aspermatogenic effect have shown that C3'p and C5'p inhibit significantly this biological action of BS-RNase. PMID:19643512

  7. Dynamic neural networks for real-time water level predictions of sewerage systems-covering gauged and ungauged sites

    Directory of Open Access Journals (Sweden)

    Yen-Ming Chiang

    2010-07-01

    Full Text Available In this research, we propose recurrent neural networks (RNNs to build a relationship between rainfalls and water level patterns of an urban sewerage system based on historical torrential rain/storm events. The RNN allows signals to propagate in both forward and backward directions, which offers the network dynamic memories. Besides, the information at the current time-step with a feedback operation can yield a time-delay unit that provides internal input information at the next time-step to effectively deal with time-varying systems. The RNN is implemented at both gauged and ungauged sites for 5-, 10-, 15-, and 20-min-ahead water level predictions. The results show that the RNN is capable of learning the nonlinear sewerage system and producing satisfactory predictions at the gauged sites. Concerning the ungauged sites, there are no historical data of water level to support prediction. In order to overcome such problem, a set of synthetic data, generated from a storm water management model (SWMM under cautious verification process of applicability based on the data from nearby gauging stations, are introduced as the learning target to the training procedure of the RNN and moreover evaluating the performance of the RNN at the ungauged sites. The results demonstrate that the potential role of the SWMM coupled with nearby rainfall and water level information can be of great use in enhancing the capability of the RNN at the ungauged sites. Hence we can conclude that the RNN is an effective and suitable model for successfully predicting the water levels at both gauged and ungauged sites in urban sewerage systems.

  8. ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Blow, Matthew J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Ren, Bing; Rubin, Edward M.; Pennacchio, Len A.

    2009-02-01

    A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

  9. Human population and activities in Forsmark. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced.The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations.The data in this description is essential for future evaluations of the impact on the environment and its human population (Environmental Impact Assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments.The actual area for the study is in this report called 'the Forsmark area', an area of 19.5 km{sup 2} near Forsmark nuclear power plant. The land use in the Forsmark area differs notably from the land use in Uppsala laen (laen = county). Only 0.04% of the total area is developed (built-up) compared to 4.9% in Uppsala laen and only 4% is agricultural land compared to 25% in the county. Furthermore, there are far more forest, wetlands and water areas in the Forsmark area. The forest area represents as much as 72.5% of the total area.The Forsmark area is uninhabited, and its surroundings are very sparsely populated. In 2002, the population density in Forsmark was 1.8 inhabitants per square kilometre, which was 24 times lower than in Uppsala laen. The population density in the

  10. Human population and activities in Forsmark. Site description

    International Nuclear Information System (INIS)

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced.The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations.The data in this description is essential for future evaluations of the impact on the environment and its human population (Environmental Impact Assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments.The actual area for the study is in this report called 'the Forsmark area', an area of 19.5 km2 near Forsmark nuclear power plant. The land use in the Forsmark area differs notably from the land use in Uppsala laen (laen = county). Only 0.04% of the total area is developed (built-up) compared to 4.9% in Uppsala laen and only 4% is agricultural land compared to 25% in the county. Furthermore, there are far more forest, wetlands and water areas in the Forsmark area. The forest area represents as much as 72.5% of the total area.The Forsmark area is uninhabited, and its surroundings are very sparsely populated. In 2002, the population density in Forsmark was 1.8 inhabitants per square kilometre, which was 24 times lower than in Uppsala laen. The population density in the parish has been

  11. Identification of Active Edge Sites for Electrochemical H2 Evolution from MoS2 Nanocatalysts

    DEFF Research Database (Denmark)

    Jaramillo, Thomas; Jørgensen, Kristina Pilt; Bonde, Jacob;

    2007-01-01

    The identification of the active sites in heterogeneous catalysis requires a combination of surface sensitive methods and reactivity studies. We determined the active site for hydrogen evolution, a reaction catalyzed by precious metals, on nanoparticulate molybdenum disulfide (MoS2) by atomically...... resolving the surface of this catalyst before measuring electrochemical activity in solution. By preparing MoS2 nanoparticles of different sizes, we systematically varied the distribution of surface sites on MoS2 nanoparticles on Au(111), which we quantified with scanning tunneling microscopy....... Electrocatalytic activity measurements for hydrogen evolution correlate linearly with the number of edge sites on the MoS2 catalyst....

  12. Preliminary siting activities for new waste handling facilities at the Idaho National Engineering Laboratory

    International Nuclear Information System (INIS)

    The Idaho Waste Processing Facility, the Mixed and Low-Level Waste Treatment Facility, and the Mixed and Low-Level Waste Disposal Facility are new waste treatment, storage, and disposal facilities that have been proposed at the Idaho National Engineering Laboratory (INEL). A prime consideration in planning for such facilities is the selection of a site. Since spring of 1992, waste management personnel at the INEL have been involved in activities directed to this end. These activities have resulted in the (a) identification of generic siting criteria, considered applicable to either treatment or disposal facilities for the purpose of preliminary site evaluations and comparisons, (b) selection of six candidate locations for siting,and (c) site-specific characterization of candidate sites relative to selected siting criteria. This report describes the information gathered in the above three categories for the six candidate sites. However, a single, preferred site has not yet been identified. Such a determination requires an overall, composite ranking of the candidate sites, which accounts for the fact that the sites under consideration have different advantages and disadvantages, that no single site is superior to all the others in all the siting criteria, and that the criteria should be assigned different weighing factors depending on whether a site is to host a treatment or a disposal facility. Stakeholder input should now be solicited to help guide the final selection. This input will include (a) siting issues not already identified in the siting, work to date, and (b) relative importances of the individual siting criteria. Final site selection will not be completed until stakeholder input (from the State of Idaho, regulatory agencies, the public, etc.) in the above areas has been obtained and a strategy has been developed to make a composite ranking of all candidate sites that accounts for all the siting criteria

  13. Preliminary siting activities for new waste handling facilities at the Idaho National Engineering Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, D.D.; Hoskinson, R.L.; Kingsford, C.O.; Ball, L.W.

    1994-09-01

    The Idaho Waste Processing Facility, the Mixed and Low-Level Waste Treatment Facility, and the Mixed and Low-Level Waste Disposal Facility are new waste treatment, storage, and disposal facilities that have been proposed at the Idaho National Engineering Laboratory (INEL). A prime consideration in planning for such facilities is the selection of a site. Since spring of 1992, waste management personnel at the INEL have been involved in activities directed to this end. These activities have resulted in the (a) identification of generic siting criteria, considered applicable to either treatment or disposal facilities for the purpose of preliminary site evaluations and comparisons, (b) selection of six candidate locations for siting,and (c) site-specific characterization of candidate sites relative to selected siting criteria. This report describes the information gathered in the above three categories for the six candidate sites. However, a single, preferred site has not yet been identified. Such a determination requires an overall, composite ranking of the candidate sites, which accounts for the fact that the sites under consideration have different advantages and disadvantages, that no single site is superior to all the others in all the siting criteria, and that the criteria should be assigned different weighing factors depending on whether a site is to host a treatment or a disposal facility. Stakeholder input should now be solicited to help guide the final selection. This input will include (a) siting issues not already identified in the siting, work to date, and (b) relative importances of the individual siting criteria. Final site selection will not be completed until stakeholder input (from the State of Idaho, regulatory agencies, the public, etc.) in the above areas has been obtained and a strategy has been developed to make a composite ranking of all candidate sites that accounts for all the siting criteria.

  14. 78 FR 33908 - Commercial Wind Lease Issuance and Site Assessment Activities on the Atlantic Outer Continental...

    Science.gov (United States)

    2013-06-05

    ... renewable energy leases and subsequent site characterization activities (geophysical, geotechnical, archaeological, and biological surveys needed to develop specific project proposals on those leases) in an... from leasing, site characterization, and site assessment in and around the Call Area (76 FR 51391)....

  15. Using Geoarchaeology to Predict the Presence of Offshore Sites in Southern California (Invited)

    Science.gov (United States)

    Hildebrand, J.; York, A.

    2013-12-01

    During the late Pleistocene and early Holocene, the continental shelves off southern California were exposed and available for occupation by prehistoric peoples. Subsequent sealevel rise and marine transgression of the continental shelf resulted in both submergence and potentially reworking of site materials. A model has been developed and tested for continental shelf site locations, using geoarchaeological methods including seismic reflection imaging, coring, and invertebrate fossil identification. In this model, such factors as topography, rate of sea level rise, sediment thickness and context of deposition are all applied to the assessment of potential for site presence and preservation. The most desirable locations for site preservation are found in offshore valley floors and flanks, whereas adjacent uplands are prone to site erosion. Cultural materials from the La Jollan Complex were recovered from two separate offshore sites by large-scale dredging operations. Transgression at these sites occurred prior to about 8000 B.P.. The relation of these cultural materials to the offshore site location model will be discussed.

  16. Unusual adsorption site behavior in PCN-14 metal-organic framework predicted from Monte Carlo simulation.

    Science.gov (United States)

    Lucena, Sebastião M P; Mileo, Paulo G M; Silvino, Pedro F G; Cavalcante, Célio L

    2011-12-01

    The adsorption equilibrium of methane in PCN-14 was simulated by the Monte Carlo technique in the grand canonical ensemble. A new force field was proposed for the methane/PCN-14 system, and the temperature dependence of the molecular siting was investigated. A detailed study of the statistics of the center of mass and potential energy showed a surprising site behavior with no energy barriers between weak and strong sites, allowing open metal sites to guide methane molecules to other neighboring sites. Moreover, this study showed that a model assuming weakly adsorbing open metal clusters in PCN-14, densely populated only at low temperatures (below 150 K), can explain published experimental data. These results also explain previously observed discrepancies between neutron diffraction experiments and Monte Carlo simulations.

  17. ProBiS-CHARMMing: Web Interface for Prediction and Optimization of Ligands in Protein Binding Sites.

    Science.gov (United States)

    Konc, Janez; Miller, Benjamin T; Štular, Tanja; Lešnik, Samo; Woodcock, H Lee; Brooks, Bernard R; Janežič, Dušanka

    2015-11-23

    Proteins often exist only as apo structures (unligated) in the Protein Data Bank, with their corresponding holo structures (with ligands) unavailable. However, apoproteins may not represent the amino-acid residue arrangement upon ligand binding well, which is especially problematic for molecular docking. We developed the ProBiS-CHARMMing web interface by connecting the ProBiS ( http://probis.cmm.ki.si ) and CHARMMing ( http://www.charmming.org ) web servers into one functional unit that enables prediction of protein-ligand complexes and allows for their geometry optimization and interaction energy calculation. The ProBiS web server predicts ligands (small compounds, proteins, nucleic acids, and single-atom ligands) that may bind to a query protein. This is achieved by comparing its surface structure against a nonredundant database of protein structures and finding those that have binding sites similar to that of the query protein. Existing ligands found in the similar binding sites are then transposed to the query according to predictions from ProBiS. The CHARMMing web server enables, among other things, minimization and potential energy calculation for a wide variety of biomolecular systems, and it is used here to optimize the geometry of the predicted protein-ligand complex structures using the CHARMM force field and to calculate their interaction energies with the corresponding query proteins. We show how ProBiS-CHARMMing can be used to predict ligands and their poses for a particular binding site, and minimize the predicted protein-ligand complexes to obtain representations of holoproteins. The ProBiS-CHARMMing web interface is freely available for academic users at http://probis.nih.gov.

  18. Predicting ambient aerosol thermal-optical reflectance (TOR) measurements from infrared spectra: extending the predictions to different years and different sites

    Science.gov (United States)

    Reggente, Matteo; Dillner, Ann M.; Takahama, Satoshi

    2016-02-01

    Organic carbon (OC) and elemental carbon (EC) are major components of atmospheric particulate matter (PM), which has been associated with increased morbidity and mortality, climate change, and reduced visibility. Typically OC and EC concentrations are measured using thermal-optical methods such as thermal-optical reflectance (TOR) from samples collected on quartz filters. In this work, we estimate TOR OC and EC using Fourier transform infrared (FT-IR) absorbance spectra from polytetrafluoroethylene (PTFE Teflon) filters using partial least square regression (PLSR) calibrated to TOR OC and EC measurements for a wide range of samples. The proposed method can be integrated with analysis of routinely collected PTFE filter samples that, in addition to OC and EC concentrations, can concurrently provide information regarding the functional group composition of the organic aerosol. We have used the FT-IR absorbance spectra and TOR OC and EC concentrations collected in the Interagency Monitoring of PROtected Visual Environments (IMPROVE) network (USA). We used 526 samples collected in 2011 at seven sites to calibrate the models, and more than 2000 samples collected in 2013 at 17 sites to test the models. Samples from six sites are present both in the calibration and test sets. The calibrations produce accurate predictions both for samples collected at the same six sites present in the calibration set (R2 = 0.97 and R2 = 0.95 for OC and EC respectively), and for samples from 9 of the 11 sites not included in the calibration set (R2 = 0.96 and R2 = 0.91 for OC and EC respectively). Samples collected at the other two sites require a different calibration model to achieve accurate predictions. We also propose a method to anticipate the prediction error; we calculate the squared Mahalanobis distance in the feature space (scores determined by PLSR) between new spectra and spectra in the calibration set. The squared Mahalanobis distance provides a crude method for assessing the

  19. Human population and activities at Simpevarp. Site description

    International Nuclear Information System (INIS)

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km2 near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km2, three times lower than in Kalmar laen. The demography statistics show no

  20. Human population and activities at Simpevarp. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km{sup 2} near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km{sup 2}, three times lower than in Kalmar laen. The

  1. Human population and activities at Simpevarp. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km{sup 2} near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km{sup 2}, three times lower than in Kalmar laen. The

  2. Site- and horizon-specific patterns of microbial community structure and enzyme activities in permafrost-affected soils of Greenland

    DEFF Research Database (Denmark)

    Gittel, Antje; Barta, Jiri; Kohoutova, Iva;

    2014-01-01

    on its impact on the carbon budget are thus still highly uncertain. However, the fate of OC is not only determined by abiotic factors, but closely tied to microbial activity. We investigated eight soil profiles in northeast Greenland comprising two sites with typical tundra vegetation and one wet fen......Permafrost-affected soils in the Northern latitudes store huge amounts of organic carbon (OC) that is prone to microbial degradation and subsequent release of greenhouse gases to the atmosphere. In Greenland, the consequences of permafrost thaw have only recently been addressed, and predictions......, diversity and activity, the wet fen site exhibiting higher potential enzyme activities and presumably being a hot spot for anaerobic degradation processes such as fermentation and methanogenesis. Lowest fungal to bacterial ratios were found in topsoils that had been relocated by cryoturbation (“buried...

  3. Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yinglong [ORNL; Baudry, Jerome Y [ORNL

    2011-01-01

    Long-timescale molecular dynamics simulations (300 ns) are performed on both the apo- (i.e., camphor-free) and camphor-bound cytochrome P450cam (CYP101). Water diffusion into and out of the protein active site is observed without biased sampling methods. During the course of the molecular dynamics simulation, an average of 6.4 water molecules is observed in the camphor-binding site of the apo form, compared to zero water molecules in the binding site of the substrate-bound form, in agreement with the number of water molecules observed in crystal structures of the same species. However, as many as 12 water molecules can be present at a given time in the camphor-binding region of the active site in the case of apo-P450cam, revealing a highly dynamic process for hydration of the protein active site, with water molecules exchanging rapidly with the bulk solvent. Water molecules are also found to exchange locations frequently inside the active site, preferentially clustering in regions surrounding the water molecules observed in the crystal structure. Potential-of-mean-force calculations identify thermodynamically favored trans-protein pathways for the diffusion of water molecules between the protein active site and the bulk solvent. Binding of camphor in the active site modifies the free-energy landscape of P450cam channels toward favoring the diffusion of water molecules out of the protein active site.

  4. Symmetrical 1-pyrrolidineacetamide showing anti-HIV activity through a new binding site on HIV-1 integrase

    Institute of Scientific and Technical Information of China (English)

    Li DU; Ya-xue ZHAO; Liu-meng YANG; Yong-tang ZHENG; Yun TANG; Xu SHEN; Hua-liang JIANG

    2008-01-01

    Aim:To characterize the functional and pharmacological features of a symmetrical 1-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene) bis-1-pyrrolidineacetamide,as a new anti-HIV compound which could competitively inhibit HIV-1 integrase (IN) binding to viral DNA.Methods:A surface plasma resonance (SPR)-based competitive assay was employed to determine the compound's inhibitory activity,and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell assay was used to qualify the antiviral activity.The potential binding sites were predicted by molecular modeling and determined by site-directed mutagenesis and a SPR binding assay.Results:l-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene) bis-1-pyrrolidineacetamide could competitively inhibit IN binding to viral DNA with a 50% inhibitory concentration (IC50) value of 7.29±0.68 μmol/L as investigated by SPR-based investigation.Another antiretroviral activity assay showed that this compound exhibited inhibition against HⅣ-Ⅰ(ⅢB) replication with a 50% effective concentration (EC50) value of 40.54 μmol/L in C8166 cells,and cytotoxicity with a cytotoxic concentration value of 173.84 μmol/L in mock-infected C8166 cells.Molecular docking predicted 3 potential residues as 1-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene)bis-1-pyrrolidineacetamide binding sites.The importance of 3 key amino acid residues (Lys103,Lys173,and Thr174) involved in the binding was further identified by site-directed mutagenesis and a SPR binding assay.Conclusion:This present work identified a new anti-HIV compound through a new IN-binding site which is expected to supply new potential drug-binding site information for HIV-1 integrase inhibitor discovery and development.

  5. Predicting Nonlinear Site Response Using Spectral Acceleration Vs PGV/Vs30: A Case History Using the Volvi-Test Site

    Science.gov (United States)

    Guéguen, Philippe

    2016-06-01

    In this study, we analyze the efficiency of the ratio between particle velocity and shear wave velocity as a strain proxy for evaluating the nonlinear seismic response of sediments. The in situ stress-strain relationships are derived from accelerometric vertical array recordings at the TST site in Volvi (Thessaloniki, Greece). First, the shear wave velocity between two successive sensors was computed by seismic interferometry and strain was computed as the velocity ratio or the relative displacement between sensors. The shear-wave velocity profile and in situ shear modulus degradation curve with strain were compared with previous studies performed at the TST site. Finally, the stress-strain relationships were derived from data recorded at the surface by extending the strain proxy and stress values to the ratio between peak ground velocity and the Vs30 parameter used for site classification, i.e. without requiring the accelerometric vertical array. Our model captures the in situ nonlinear response of the site, without consideration of azimuth or distance of the earthquakes. In conclusion, the acceleration (stress) values, based on the accelerometric response spectra instead of peak ground acceleration compared with the deformation (strain) proxy, provide an effective model of the in situ nonlinear response, providing information that can be integrated into ground motion prediction equations.

  6. Predicting anti-androgenic activity of bisphenols using molecular docking and quantitative structure-activity relationships.

    Science.gov (United States)

    Yang, Xianhai; Liu, Huihui; Yang, Qian; Liu, Jining; Chen, Jingwen; Shi, Lili

    2016-11-01

    Both in vivo and in vitro assay indicated that bisphenols can inhibit the androgen receptor. However, the underlying antagonistic mechanism is unclear. In this study, molecular docking was employed to probe the interaction mechanism between bisphenols and human androgen receptor (hAR). The binding pattern of ligands in hAR crystal structures was also analyzed. Results show that hydrogen bonding and hydrophobic interactions are the dominant interactions between the ligands and hAR. The critical amino acid residues involved in forming hydrogen bonding between bisphenols and hAR is Asn 705 and Gln 711. Furthermore, appropriate molecular structural descriptors were selected to characterize the non-bonded interactions. Stepwise multiple linear regressions (MLR) analysis was employed to develop quantitative structure-activity relationship (QSAR) models for predicting the anti-androgenic activity of bisphenols. Based on the QSAR development and validation guideline issued by OECD, the goodness-of-fit, robustness and predictive ability of constructed QSAR model were assessed. The model application domain was characterized by the Euclidean distance and Williams plot. The mechanisms of the constructed model were also interpreted based on the selected molecular descriptors i.e. the number of hydroxyl groups (nROH), the most positive values of the molecular surface potential (Vs,max) and the lowest unoccupied molecular orbital energy (ELUMO). Finally, based on the model developed, the data gap for other twenty-six bisphenols on their anti-androgenic activity was filled. The predicted results indicated that the anti-androgenic activity of seven bisphenols was higher than that of bisphenol A. PMID:27561732

  7. Blogs and Social Network Sites as Activity Systems: Exploring Adult Informal Learning Process through Activity Theory Framework

    Science.gov (United States)

    Heo, Gyeong Mi; Lee, Romee

    2013-01-01

    This paper uses an Activity Theory framework to explore adult user activities and informal learning processes as reflected in their blogs and social network sites (SNS). Using the assumption that a web-based space is an activity system in which learning occurs, typical features of the components were investigated and each activity system then…

  8. Early Site Permit Demonstration Program: Recommendations for communication activities and public participation in the Early Site Permit Demonstration Program

    International Nuclear Information System (INIS)

    On October 24, 1992, President Bush signed into law the National Energy Policy Act of 1992. The bill is a sweeping, comprehensive overhaul of the Nation's energy laws, the first in more than a decade. Among other provisions, the National Energy Policy Act reforms the licensing process for new nuclear power plants by adopting a new approach developed by the US Nuclear Regulatory Commission (NRC) in 1989, and upheld in court in 1992. The NRC 10 CFR Part 52 rule is a three-step process that guarantees public participation at each step. The steps are: early site permit approval; standard design certifications; and, combined construction/operating licenses for nuclear power reactors. Licensing reform increases an organization's ability to respond to future baseload electricity generation needs with less financial risk for ratepayers and the organization. Costly delays can be avoided because design, safety and siting issues will be resolved before a company starts to build a plant. Specifically, early site permit approval allows for site suitability and acceptability issues to be addressed prior to an organization's commitment to build a plant. Responsibility for site-specific activities, including communications and public participation, rests with those organizations selected to try out early site approval. This plan has been prepared to assist those companies (referred to as sponsoring organizations) in planning their communications and public involvement programs. It provides research findings, information and recommendations to be used by organizations as a resource and starting point in developing their own plans

  9. Early Site Permit Demonstration Program: Recommendations for communication activities and public participation in the Early Site Permit Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-27

    On October 24, 1992, President Bush signed into law the National Energy Policy Act of 1992. The bill is a sweeping, comprehensive overhaul of the Nation`s energy laws, the first in more than a decade. Among other provisions, the National Energy Policy Act reforms the licensing process for new nuclear power plants by adopting a new approach developed by the US Nuclear Regulatory Commission (NRC) in 1989, and upheld in court in 1992. The NRC 10 CFR Part 52 rule is a three-step process that guarantees public participation at each step. The steps are: early site permit approval; standard design certifications; and, combined construction/operating licenses for nuclear power reactors. Licensing reform increases an organization`s ability to respond to future baseload electricity generation needs with less financial risk for ratepayers and the organization. Costly delays can be avoided because design, safety and siting issues will be resolved before a company starts to build a plant. Specifically, early site permit approval allows for site suitability and acceptability issues to be addressed prior to an organization`s commitment to build a plant. Responsibility for site-specific activities, including communications and public participation, rests with those organizations selected to try out early site approval. This plan has been prepared to assist those companies (referred to as sponsoring organizations) in planning their communications and public involvement programs. It provides research findings, information and recommendations to be used by organizations as a resource and starting point in developing their own plans.

  10. 76 FR 30696 - Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites

    Science.gov (United States)

    2011-05-26

    ... Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites AGENCY: Department of... eligible active uranium and thorium processing site licensees for reimbursement under Title X of the Energy... requires DOE to reimburse eligible uranium and thorium licensees for certain costs of...

  11. 76 FR 24871 - Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites

    Science.gov (United States)

    2011-05-03

    ... Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites AGENCY: Department of... from eligible active uranium and thorium processing site licensees for reimbursement under Title X of...). Title X requires DOE to reimburse eligible uranium and thorium licensees for certain costs...

  12. Identification of ice nucleation active sites on feldspar dust particles.

    Science.gov (United States)

    Zolles, Tobias; Burkart, Julia; Häusler, Thomas; Pummer, Bernhard; Hitzenberger, Regina; Grothe, Hinrich

    2015-03-19

    Mineral dusts originating from Earth's crust are known to be important atmospheric ice nuclei. In agreement with earlier studies, feldspar was found as the most active of the tested natural mineral dusts. Here we investigated in closer detail the reasons for its activity and the difference in the activity of the different feldspars. Conclusions are drawn from scanning electron microscopy, X-ray powder diffraction, infrared spectroscopy, and oil-immersion freezing experiments. K-feldspar showed by far the highest ice nucleation activity. Finally, we give a potential explanation of this effect, finding alkali-metal ions having different hydration shells and thus an influence on the ice nucleation activity of feldspar surfaces. PMID:25584435

  13. WAsP prediction errors due to site orography[Wind Atlas Analysis and Application Program

    Energy Technology Data Exchange (ETDEWEB)

    Bowen, A.J.; Mortensen, N.G.

    2004-12-01

    The influence of rugged terrain on the prediction accuracy of the Wind Atlas Analysis and Application Program (WAsP) is investigated using a case study of field measurements taken in rugged terrain. The parameters that could cause substantial errors in a prediction are identified and discussed. In particular, the effects from extreme orography are investigated. A suitable performance indicator is developed which predicts the sign and approximate magnitude of such errors due to orography. This procedure allows the user to assess the consequences of using WAsP outside its operating envelope and could provide a means of correction for rugged terrain effects. (au)

  14. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts.

    Science.gov (United States)

    Wang, Lu-Cun; Friend, C M; Fushimi, Rebecca; Madix, Robert J

    2016-07-01

    The activation of molecular O2 as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O2 activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O2 dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O2 dissociation is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O2 dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction. PMID:27376884

  15. Predicting functional divergence in protein evolution by site-specific rate shifts

    Science.gov (United States)

    Gaucher, Eric A.; Gu, Xun; Miyamoto, Michael M.; Benner, Steven A.

    2002-01-01

    Most modern tools that analyze protein evolution allow individual sites to mutate at constant rates over the history of the protein family. However, Walter Fitch observed in the 1970s that, if a protein changes its function, the mutability of individual sites might also change. This observation is captured in the "non-homogeneous gamma model", which extracts functional information from gene families by examining the different rates at which individual sites evolve. This model has recently been coupled with structural and molecular biology to identify sites that are likely to be involved in changing function within the gene family. Applying this to multiple gene families highlights the widespread divergence of functional behavior among proteins to generate paralogs and orthologs.

  16. In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations.

    Science.gov (United States)

    Klopman, G; Li, J Y; Wang, S; Pearson, A J; Chang, K; Jacobs, M R; Bajaksouzian, S; Ellner, J J

    1994-08-01

    The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.

  17. Performance predictions for mechanical excavators in Yucca Mountain tuffs; Yucca Mountain Site Characterization Project

    Energy Technology Data Exchange (ETDEWEB)

    Ozdemir, L.; Gertsch, L.; Neil, D.; Friant, J. [Colorado School of Mines, Golden, CO (United States). Earth Mechanics Inst.

    1992-09-01

    The performances of several mechanical excavators are predicted for use in the tuffs at Yucca Mountain: Tunnel boring machines, the Mobile Miner, a roadheader, a blind shaft borer, a vertical wheel shaft boring machine, raise drills, and V-Moles. Work summarized is comprised of three parts: Initial prediction using existing rock physical property information; Measurement of additional rock physical properties; and Revision of the initial predictions using the enhanced database. The performance predictions are based on theoretical and empirical relationships between rock properties and the forces-experienced by rock cutters and bits during excavation. Machine backup systems and excavation design aspects, such as curves and grades, are considered in determining excavator utilization factors. Instanteous penetration rate, advance rate, and cutter costs are the fundamental performance indicators.

  18. Structure-based comparative analysis and prediction of N-linked glycosylation sites in evolutionarily distant eukaryotes.

    Science.gov (United States)

    Lam, Phuc Vinh Nguyen; Goldman, Radoslav; Karagiannis, Konstantinos; Narsule, Tejas; Simonyan, Vahan; Soika, Valerii; Mazumder, Raja

    2013-04-01

    The asparagine-X-serine/threonine (NXS/T) motif, where X is any amino acid except proline, is the consensus motif for N-linked glycosylation. Significant numbers of high-resolution crystal structures of glycosylated proteins allow us to carry out structural analysis of the N-linked glycosylation sites (NGS). Our analysis shows that there is enough structural information from diverse glycoproteins to allow the development of rules which can be used to predict NGS. A Python-based tool was developed to investigate asparagines implicated in N-glycosylation in five species: Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana and Saccharomyces cerevisiae. Our analysis shows that 78% of all asparagines of NXS/T motif involved in N-glycosylation are localized in the loop/turn conformation in the human proteome. Similar distribution was revealed for all the other species examined. Comparative analysis of the occurrence of NXS/T motifs not known to be glycosylated and their reverse sequence (S/TXN) shows a similar distribution across the secondary structural elements, indicating that the NXS/T motif in itself is not biologically relevant. Based on our analysis, we have defined rules to determine NGS. Using machine learning methods based on these rules we can predict with 93% accuracy if a particular site will be glycosylated. If structural information is not available the tool uses structural prediction results resulting in 74% accuracy. The tool was used to identify glycosylation sites in 108 human proteins with structures and 2247 proteins without structures that have acquired NXS/T site/s due to non-synonymous variation. The tool, Structure Feature Analysis Tool (SFAT), is freely available to the public at http://hive.biochemistry.gwu.edu/tools/sfat. PMID:23459159

  19. Assessment of former uranium sites and their ongoing remediation activities

    International Nuclear Information System (INIS)

    Carried out analysis on tailing's buildings operation shows that period for engineer barrier service, taking into account any catastrophic natural impacts, is too little in comparison with life-time of long-live radionuclides. Priorities should be defined by danger degree and isolation costs (protection optimization), therefore uncommon, non-traditional methods, developed taking into account natural factors for long-live waste (radionuclides) isolation are necessary. That's why, it is necessary to carry out specialized research and development, design and exploratory and other works on monitoring of social-ecological condition of these sites, as well as on demographic public diseases, living in these regions.

  20. Protein engineering of alcohol dehydrogenase--1. Effects of two amino acid changes in the active site of yeast ADH-1.

    Science.gov (United States)

    Murali, C; Creaser, E H

    1986-01-01

    One of the promises held out by protein engineering is the ability to alter predictably the properties of an enzyme to enable it to find new substrates or catalyse existing substrates more efficiently, such manipulations being of interest both enzymologically and, potentially, industrially. It has been postulated that in yeast alcohol dehydrogenase (YADH-1) certain amino acids such as Trp 93 and Thr 48 constrict the active site due to their bulky side chains and thus impede catalysis of molecules larger than ethanol. To study effects of enlarging the active site we have made two changes into YADH-1, replacing Trp 93 with Phe and Thr 48 with Ser. Kinetic experiments showed that this enzyme had marked increases in reaction velocity for the n-alcohols propanol, butanol, pentanol, hexanol, heptanol, octanol and cinnamyl alcohol compared to the parent, agreeing with the prediction that expanding the active site should facilitate the oxidation of larger alcohols. The substrate affinities were slightly reduced in the altered enzyme, possibly due to its having reduced hydrophobicity at Phe 93.

  1. Perturbation Approaches for Exploring Protein Binding Site Flexibility to Predict Transient Binding Pockets.

    Science.gov (United States)

    Kokh, Daria B; Czodrowski, Paul; Rippmann, Friedrich; Wade, Rebecca C

    2016-08-01

    Simulations of the long-time scale motions of a ligand binding pocket in a protein may open up new perspectives for the design of compounds with steric or chemical properties differing from those of known binders. However, slow motions of proteins are difficult to access using standard molecular dynamics (MD) simulations and are thus usually neglected in computational drug design. Here, we introduce two nonequilibrium MD approaches to identify conformational changes of a binding site and detect transient pockets associated with these motions. The methods proposed are based on the rotamerically induced perturbation (RIP) MD approach, which employs perturbation of side-chain torsional motion for initiating large-scale protein movement. The first approach, Langevin-RIP (L-RIP), entails a series of short Langevin MD simulations, each starting with perturbation of one of the side-chains lining the binding site of interest. L-RIP provides extensive sampling of conformational changes of the binding site. In less than 1 ns of MD simulation with L-RIP, we observed distortions of the α-helix in the ATP binding site of HSP90 and flipping of the DFG loop in Src kinase. In the second approach, RIPlig, a perturbation is applied to a pseudoligand placed in different parts of a binding pocket, which enables flexible regions of the binding site to be identified in a small number of 10 ps MD simulations. The methods were evaluated for four test proteins displaying different types and degrees of binding site flexibility. Both methods reveal all transient pocket regions in less than a total of 10 ns of simulations, even though many of these regions remained closed in 100 ns conventional MD. The proposed methods provide computationally efficient tools to explore binding site flexibility and can aid in the functional characterization of protein pockets, and the identification of transient pockets for ligand design. PMID:27399277

  2. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer;

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example......, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting...

  3. Lipolytic activity from bacteria prospected in polluted portuary sites

    Directory of Open Access Journals (Sweden)

    Kaori Levy Fonseca

    2014-06-01

    The aim of this study was to isolate and identify the TBT resistant marine bacteria capable to produce extracellular lipases and then test the lipolytic activity of their extracts. For this purpose, TBT resistant bacteria (able to grow at 3 mM TBT from 7 Portuguese harbors were collected (Póvoa de Varzim (V; 41.376120,-8.766945, Leixões (L; 41.195238,- 8.684177, Aveiro (A; 40.645899,-8.727098, Figueira da Foz (F; 40.146848,-8.849176, Peniche (P; 39.355422,-9.375479, Setúbal (St; 38.521228,-8.887277 e Sines (S; 37.950219,-8.864599, isolated and then REP-PCR characterized. Their extracellular lipase activity was assayed by the method of Rhodamine B in solid culture medium. Rhodamine is a dye which together with fatty acids released by the hydrolysis of triacylglycerols, forms a fluorescent complex when exposed to ultraviolet light. The use of this test was due to its sensitivity in detecting lipase activity even in organisms with low production of extracellular lipases. Lipolytic extracts activities were estimated using p-nitrophenyl palmitate method for optimization of activity conditions. This highly sensitive spectrophotometric method estimates the amount of p-nitrophenol (p-NP released during the hydrolysis of the substrate p-nitrophenyl palmitate (p-NPP. Isolates producing extracellular lipases were then identified by MALDI-TOF-M

  4. Nestling activity levels during begging behaviour predicts activity level and body mass in adulthood

    Directory of Open Access Journals (Sweden)

    Luke S.C. McCowan

    2014-09-01

    Full Text Available Across a range of species including humans, personality traits, or differences in behaviour between individuals that are consistent over time, have been demonstrated. However, few studies have measured whether these consistent differences are evident in very young animals, and whether they persist over an individual’s entire lifespan. Here we investigated the begging behaviour of very young cross-fostered zebra finch nestlings and the relationship between that and adult activity levels. We found a link between the nestling activity behaviour head movements during begging, measured at just five and seven days after hatching, and adult activity levels, measured when individuals were between three and three and a half years old. Moreover, body mass was found to be negatively correlated with both nestling and adult activity levels, suggesting that individuals which carry less body fat as adults are less active both as adults and during begging as nestlings. Our work suggests that the personality traits identified here in both very young nestlings and adults may be linked to physiological factors such as metabolism or environmental sources of variation. Moreover, our work suggests it may be possible to predict an individual’s future adult personality at a very young age, opening up new avenues for future work to explore the relationship between personality and a number of aspects of individual life history and survival.

  5. Nestling activity levels during begging behaviour predicts activity level and body mass in adulthood.

    Science.gov (United States)

    McCowan, Luke S C; Griffith, Simon C

    2014-01-01

    Across a range of species including humans, personality traits, or differences in behaviour between individuals that are consistent over time, have been demonstrated. However, few studies have measured whether these consistent differences are evident in very young animals, and whether they persist over an individual's entire lifespan. Here we investigated the begging behaviour of very young cross-fostered zebra finch nestlings and the relationship between that and adult activity levels. We found a link between the nestling activity behaviour head movements during begging, measured at just five and seven days after hatching, and adult activity levels, measured when individuals were between three and three and a half years old. Moreover, body mass was found to be negatively correlated with both nestling and adult activity levels, suggesting that individuals which carry less body fat as adults are less active both as adults and during begging as nestlings. Our work suggests that the personality traits identified here in both very young nestlings and adults may be linked to physiological factors such as metabolism or environmental sources of variation. Moreover, our work suggests it may be possible to predict an individual's future adult personality at a very young age, opening up new avenues for future work to explore the relationship between personality and a number of aspects of individual life history and survival. PMID:25279258

  6. Characterization of an Active Thermal Erosion Site, Caribou Creek, Alaska

    Science.gov (United States)

    Busey, R.; Bolton, W. R.; Cherry, J. E.; Hinzman, L. D.

    2013-12-01

    The goal of this project is to estimate volume loss of soil over time from this site, provide parameterizations on erodibility of ice rich permafrost and serve as a baseline for future landscape evolution simulations. Located in the zone of discontinuous permafrost, the interior region of Alaska (USA) is home to a large quantity of warm, unstable permafrost that is both high in ice content and has soil temperatures near the freezing point. Much of this permafrost maintains a frozen state despite the general warming air temperature trend in the region due to the presence of a thick insulating organic mat and a dense root network in the upper sub-surface of the soil column. At a rapidly evolving thermo-erosion site, located within the Caribou-Poker Creeks Research Watershed (part of the Bonanza Creek LTER) near Chatanika, Alaska (N65.140, W147.570), the protective organic layer and associated plants were disturbed by an adjacent traditional use trail and the shifting of a groundwater spring. These triggers have led to rapid geomorphological change on the landscape as the soil thaws and sediment is transported into the creek at the valley bottom. Since 2006 (approximately the time of initiation), the thermal erosion has grown to 170 meters length, 3 meters max depth, and 15 meters maximum width. This research combines several data sets: DGPS survey, imagery from an extremely low altitude pole-based remote sensing (3 to 5 meters above ground level), and imagery from an Unmanned Aerial System (UAS) at about 60m altitude.

  7. Evolution of neural networks for the prediction of hydraulic conductivity as a function of borehole geophysical logs: Shobasama site, Japan.

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, Paul C.; McKenna, Sean Andrew

    2004-06-01

    This report describes the methodology and results of a project to develop a neural network for the prediction of the measured hydraulic conductivity or transmissivity in a series of boreholes at the Tono, Japan study site. Geophysical measurements were used as the input to EL feed-forward neural network. A simple genetic algorithm was used to evolve the architecture and parameters of the neural network in conjunction with an optimal subset of geophysical measurements for the prediction of hydraulic conductivity. The first attempt was focused on the estimation of the class of the hydraulic conductivity, high, medium or low, from the geophysical logs. This estimation was done while using the genetic algorithm to simultaneously determine which geophysical logs were the most important and optimizing the architecture of the neural network. Initial results showed that certain geophysical logs provided more information than others- most notably the 'short-normal', micro-resistivity, porosity and sonic logs provided the most information on hydraulic conductivity. The neural network produced excellent training results with accuracy of 90 percent or greater, but was unable to produce accurate predictions of the hydraulic conductivity class. The second attempt at prediction was done using a new methodology and a modified data set. The new methodology builds on the results of the first attempts at prediction by limiting the choices of geophysical logs to only those that provide significant information. Additionally, this second attempt uses a modified data set and predicts transmissivity instead of hydraulic conductivity. Results of these simulations indicate that the most informative geophysical measurements for the prediction of transmissivity are depth and sonic log. The long normal resistivity and self potential borehole logs are moderately informative. In addition, it was found that porosity and crack counts (clear, open, or hairline) do not inform predictions

  8. Molecular Basis for Enzymatic Sulfite Oxidation -- HOW THREE CONSERVED ACTIVE SITE RESIDUES SHAPE ENZYME ACTIVITY

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Susan; Rapson, Trevor; Johnson-Winters, Kayunta; Astashkin, Andrei; Enemark, John; Kappler, Ulrike

    2008-11-10

    Sulfite dehydrogenases (SDHs) catalyze the oxidation and detoxification of sulfite to sulfate, a reaction critical to all forms of life. Sulfite-oxidizing enzymes contain three conserved active site amino acids (Arg-55, His-57, and Tyr-236) that are crucial for catalytic competency. Here we have studied the kinetic and structural effects of two novel and one previously reported substitution (R55M, H57A, Y236F) in these residues on SDH catalysis. Both Arg-55 and His-57 were found to have key roles in substrate binding. An R55M substitution increased Km(sulfite)(app) by 2-3 orders of magnitude, whereas His-57 was required for maintaining a high substrate affinity at low pH when the imidazole ring is fully protonated. This effect may be mediated by interactions of His-57 with Arg-55 that stabilize the position of the Arg-55 side chain or, alternatively, may reflect changes in the protonation state of sulfite. Unlike what is seen for SDHWT and SDHY236F, the catalytic turnover rates of SDHR55M and SDHH57A are relatively insensitive to pH (~;;60 and 200 s-1, respectively). On the structural level, striking kinetic effects appeared to correlate with disorder (in SDHH57A and SDHY236F) or absence of Arg-55 (SDHR55M), suggesting that Arg-55 and the hydrogen bonding interactions it engages in are crucial for substrate binding and catalysis. The structure of SDHR55M has sulfate bound at the active site, a fact that coincides with a significant increase in the inhibitory effect of sulfate in SDHR55M. Thus, Arg-55 also appears to be involved in enabling discrimination between the substrate and product in SDH.

  9. Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP.

    Science.gov (United States)

    Miner, Kyle D; Kurtz, Donald M

    2016-02-16

    HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.

  10. Surface binding sites in carbohydrate active enzymes: An emerging picture of structural and functional diversity

    DEFF Research Database (Denmark)

    Svensson, Birte; Cockburn, Darrell

    2013-01-01

    Carbohydrate active enzymes, particularly those that are active on polysaccharides, are often found associated with carbohydrate binding modules (CBMs), which can play several roles in supporting enzyme function, such as localizing the enzyme to the substrate. However, the presence of CBMs...... is not universal and is in fact rare among some families of enzymes. In some cases an alternative to possessing a CBM is for the enzyme to bind to the substrate at a site on the catalytic domain, but away from the active site. Such a site is termed a surface (or secondary) binding site (SBS). SBSs have been...... identified in enzymes from a wide variety of families, though almost half are found in the α-amylase family GH13. The roles attributed to SBSs are not limited to targeting the enzyme to the substrate, but also include a variety of others such as guiding the substrate into the active site, altering enzyme...

  11. The landscape degradation in the mining sites with suspended activity

    Directory of Open Access Journals (Sweden)

    Anca IONCE

    2009-08-01

    Full Text Available The extracting industry, through its extraction activities, of shipping the ores, of breaking the ores, of preparing the practical substances, of stowing the useless rock, of transporting the practical substances, etc. might modify the area’s relief and the quality of ground, of thesurface waters and of the air. Suceava County has an old tradition of mining, where the results of this activity are visible, especially the visual point of view, and where not taking certain measures of ecological remediation will emphasize the disappointing image of the landscape within the areas of mining activity performing.The predominant mountainous landscape, in which mining activities have been held, is being affected also by the abandoned industrial and administrative buildings, in an advanced degradation state.The hydrographic system, very rich in mining areas, has its water quality affected by the acid rock drainage- phenomenon which appeared in many mining waste deposits.

  12. Endolysosomes Are the Principal Intracellular Sites of Acid Hydrolase Activity.

    Science.gov (United States)

    Bright, Nicholas A; Davis, Luther J; Luzio, J Paul

    2016-09-12

    The endocytic delivery of macromolecules from the mammalian cell surface for degradation by lysosomal acid hydrolases requires traffic through early endosomes to late endosomes followed by transient (kissing) or complete fusions between late endosomes and lysosomes. Transient or complete fusion results in the formation of endolysosomes, which are hybrid organelles from which lysosomes are re-formed. We have used synthetic membrane-permeable cathepsin substrates, which liberate fluorescent reporters upon proteolytic cleavage, as well as acid phosphatase cytochemistry to identify which endocytic compartments are acid hydrolase active. We found that endolysosomes are the principal organelles in which acid hydrolase substrates are cleaved. Endolysosomes also accumulated acidotropic probes and could be distinguished from terminal storage lysosomes, which were acid hydrolase inactive and did not accumulate acidotropic probes. Using live-cell microscopy, we have demonstrated that fusion events, which form endolysosomes, precede the onset of acid hydrolase activity. By means of sucrose and invertase uptake experiments, we have also shown that acid-hydrolase-active endolysosomes and acid-hydrolase-inactive, terminal storage lysosomes exist in dynamic equilibrium. We conclude that the terminal endocytic compartment is composed of acid-hydrolase-active, acidic endolysosomes and acid hydrolase-inactive, non-acidic, terminal storage lysosomes, which are linked and function in a lysosome regeneration cycle. PMID:27498570

  13. A sequence-based dynamic ensemble learning system for protein ligand-binding site prediction

    KAUST Repository

    Chen, Peng

    2015-12-03

    Background: Proteins have the fundamental ability to selectively bind to other molecules and perform specific functions through such interactions, such as protein-ligand binding. Accurate prediction of protein residues that physically bind to ligands is important for drug design and protein docking studies. Most of the successful protein-ligand binding predictions were based on known structures. However, structural information is not largely available in practice due to the huge gap between the number of known protein sequences and that of experimentally solved structures

  14. Prediction of Pathway Activation by Xenobiotic-Responsive Transcription Factors in the Mouse Liver

    Science.gov (United States)

    Many drugs and environmentally-relevant chemicals activate xenobioticresponsive transcription factors (TF). Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening. Starting with a large compendium of Affymet...

  15. Factors Predicting Physical Activity Among Children With Special Needs

    Directory of Open Access Journals (Sweden)

    Shahram Yazdani, MD

    2013-07-01

    Full Text Available Introduction Obesity is especially prevalent among children with special needs. Both lack of physical activity and unhealthful eating are major contributing factors. The objective of our study was to investigate barriers to physical activity among these children. Methods We surveyed parents of the 171 children attending Vista Del Mar School in Los Angeles, a nonprofit school serving a socioeconomically diverse group of children with special needs from kindergarten through 12th grade. Parents were asked about their child’s and their own physical activity habits, barriers to their child’s exercise, and demographics. The response rate was 67%. Multivariate logistic regression was used to examine predictors of children being physically active at least 3 hours per week. Results Parents reported that 45% of the children were diagnosed with attention deficit hyperactivity disorder, 38% with autism, and 34% with learning disabilities; 47% of children and 56% of parents were physically active less than 3 hours per week. The top barriers to physical activity were reported as child’s lack of interest (43%, lack of developmentally appropriate programs (33%, too many behavioral problems (32%, and parents’ lack of time (29%. However, child’s lack of interest was the only parent-reported barrier independently associated with children’s physical activity. Meanwhile, children whose parents were physically active at least 3 hours per week were 4.2 times as likely to be physically active as children whose parents were less physically active (P = .01. Conclusion In this group of students with special needs, children’s physical activity was strongly associated with parental physical activity; parent-reported barriers may have had less direct effect. Further studies should examine the importance of parental physical activity among children with special needs.

  16. Active site proton delivery and the lyase activity of human CYP17A1

    Energy Technology Data Exchange (ETDEWEB)

    Khatri, Yogan; Gregory, Michael C.; Grinkova, Yelena V.; Denisov, Ilia G.; Sligar, Stephen G., E-mail: s-sligar@illinois.edu

    2014-01-03

    equivalents and protons are funneled into non-productive pathways. This is similar to previous work with other P450 catalyzed hydroxylation. However, catalysis of carbon–carbon bond scission by the T306A mutant was largely unimpeded by disruption of the CYP17A1 acid-alcohol pair. The unique response of CYP17A1 lyase activity to mutation of Thr306 is consistent with a reactive intermediate formed independently of proton delivery in the active site, and supports involvement of a nucleophilic peroxo-anion rather than the traditional Compound I in catalysis.

  17. Does ecosystem sensitivity to precipitation at the site-level conform to regional-scale predictions?.

    Science.gov (United States)

    Wilcox, Kevin R; Blair, John M; Smith, Melinda D; Knapp, Alan K

    2016-03-01

    Central to understanding global C cycle dynamics is the functional relationship between precipitation and net primary production (NPP). At large spatial (regional) scales, the responsiveness of aboveground NPP (ANPP) to interannual variation in annual precipitation (AP; ANPPsens) is inversely related to site-level ANPP, coinciding with turnover of plant communities along precipitation gradients. Within ecosystems experiencing chronic alterations in water availability, plant community change will also occur with unknown consequences for ANPPsens. To examine the role plant community shifts may play in determining alterations in site-level ANPPPsens, we experimentally increased precipitation by approximately 35% for two decades in a native Central U.S. grassland. Consistent with regional models, ANPPsens decreased initially as water availability and ANPP increased. However, ANPPsens shifted back to ambient levels when mesic species increased in abundance in the plant community. Similarly, in grassland sites with distinct mesic and xeric plant communities and corresponding 50% differences in ANPP, ANPPsens did not differ over almost three decades. We conclude that responses in ANPPsens to chronic alterations in water availability within an ecosystem may not conform to regional AP-ANPP patterns, despite expected changes in ANPP and plant communities. The result is unanticipated functional resistance to climate change at the site scale. PMID:27197383

  18. Social Networking Site Use Predicts Changes in Young Adults' Psychological Adjustment

    Science.gov (United States)

    Szwedo, David E.; Mikami, Amori Yee; Allen, Joseph P.

    2012-01-01

    This study examined youths' friendships and posted pictures on social networking sites as predictors of changes in their adjustment over time. Observational, self-report, and peer-report data were obtained from a community sample of 89 young adults interviewed at age 21 and again at age 22. Findings were consistent with a leveling effect for…

  19. Right anterior superior temporal activation predicts auditory sentence comprehension following aphasic stroke.

    Science.gov (United States)

    Crinion, Jenny; Price, Cathy J

    2005-12-01

    Previous studies have suggested that recovery of speech comprehension after left hemisphere infarction may depend on a mechanism in the right hemisphere. However, the role that distinct right hemisphere regions play in speech comprehension following left hemisphere stroke has not been established. Here, we used functional magnetic resonance imaging (fMRI) to investigate narrative speech activation in 18 neurologically normal subjects and 17 patients with left hemisphere stroke and a history of aphasia. Activation for listening to meaningful stories relative to meaningless reversed speech was identified in the normal subjects and in each patient. Second level analyses were then used to investigate how story activation changed with the patients' auditory sentence comprehension skills and surprise story recognition memory tests post-scanning. Irrespective of lesion site, performance on tests of auditory sentence comprehension was positively correlated with activation in the right lateral superior temporal region, anterior to primary auditory cortex. In addition, when the stroke spared the left temporal cortex, good performance on tests of auditory sentence comprehension was also correlated with the left posterior superior temporal cortex (Wernicke's area). In distinct contrast to this, good story recognition memory predicted left inferior frontal and right cerebellar activation. The implication of this double dissociation in the effects of auditory sentence comprehension and story recognition memory is that left frontal and left temporal activations are dissociable. Our findings strongly support the role of the right temporal lobe in processing narrative speech and, in particular, auditory sentence comprehension following left hemisphere aphasic stroke. In addition, they highlight the importance of the right anterior superior temporal cortex where the response was dissociated from that in the left posterior temporal lobe.

  20. Resting alpha activity predicts learning ability in alpha neurofeedback

    OpenAIRE

    Wenya eNan; Feng eWan; Mang I eVai; Agostinho eRosa

    2014-01-01

    Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the tr...

  1. Paper Highlight: Biomarker Identified for Predicting Early Prostate Cancer Aggressiveness — Site

    Science.gov (United States)

    A team led by Cory Abate-Shen, Michael Shen, and Andrea Califano at Columbia University found that measuring the expression levels of three genes associated with aging can be used to predict the aggressiveness of seemingly low-risk prostate cancer.

  2. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren;

    1997-01-01

    We have developed a new method for the identification of signal peptides and their cleavage based on neural networks trained on separate sets of prokaryotic and eukaryotic sequence. The method performs significantly better than previous prediction schemes and can easily be applied on genome...

  3. LSD-induced entropic brain activity predicts subsequent personality change.

    Science.gov (United States)

    Lebedev, A V; Kaelen, M; Lövdén, M; Nilsson, J; Feilding, A; Nutt, D J; Carhart-Harris, R L

    2016-09-01

    Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc. PMID:27151536

  4. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    Directory of Open Access Journals (Sweden)

    Emily S W Wong

    Full Text Available Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree and developed an algorithm (SpiderP for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html, a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from

  5. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    Science.gov (United States)

    Wong, Emily S W; Hardy, Margaret C; Wood, David; Bailey, Timothy; King, Glenn F

    2013-01-01

    Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the Spider

  6. PASS-GP: Predictive active set selection for Gaussian processes

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2010-01-01

    available in GPs to make a common ranking for both active and inactive points, allowing points to be removed again from the active set. This is important for keeping the complexity down and at the same time focusing on points close to the decision boundary. We lend both theoretical and empirical support...

  7. Measuring disease activity to predict therapeutic outcome in Graves' ophthalmopathy

    NARCIS (Netherlands)

    Terwee, C.B.; Prummel, M.F.; Gerding, M.N.; Kahaly, G.J.; Dekker, F.W.; Wiersinga, W.M.

    2005-01-01

    OBJECTIVE: The concept of disease activity in Graves' ophthalmopathy (GO) might explain why as many as one-third of patients do not respond to immunosuppressive treatment, because only patients in the active stage of disease are expected to respond. The hypothesis was adopted that a parameter used t

  8. Identifying high dose activities in industrial site radiography

    International Nuclear Information System (INIS)

    Although the radiation doses received by industrial radiographers in the UK have progressively fallen over the last few years, with most now receiving less than 1 mSv/y, a few still receive, relative to the rest, much higher doses. As a percentage of all radiographers the number stays surprisingly constant from year to year. This paper describes a survey to identify the work causing these doses and suggest possible solutions. The UK Central Index of Dose Information was interrogated to identify the industrial radiography companies having staff (not necessarily the same person) with doses of greater than 5mSv/y in the last three years for which information was available. This was 15 in total. The people on the staff receiving these doses were identified and a questionnaire sent to the companies concerned requesting information about their work. A general questionnaire about the operation of the company was also included. With the agreement of the company these questionnaires were followed up by a visit to the company to interviews a number of the management and the radiographers if available. Both groups were generally very open about their problems and every discussion had a positive outcome. Several areas of work/reasons for the doses have been identified. These are: pipeline radiography, ultra sound radiographers working on nuclear reactors, complex plant work often with several teams in the area, inability to retreat from the wind out equipment due to height or access problems, site pressure to not follow the best practices and a lack of appreciation when a dose was being received or, alternatively, carelessness. Some o these problem areas are very difficult to resolve. However ways in which the Health and Safety can help influence the doses have been identified together with practical suggestions radiographers could adopt. These will be reported. (author)

  9. Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

    Science.gov (United States)

    Navez, Julie; Hubert, Catherine; Gigot, Jean-François; Navez, Benoit; Lambert, Catherine; Jamar, François; Danse, Etienne; Lannoy, Valérie; Jabbour, Nicolas

    2015-01-01

    Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by (111)Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100 × 10(9)/L, response (R) for PC≥30 × 10(9)/L and 100 versus <=100, 95% CI [0.025-0.493], p = 0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended. PMID:25275667

  10. Predictability of PV power grid performance on insular sites without weather stations: use of artificial neural networks

    CERN Document Server

    Voyant, Cyril; Paoli, Christophe; Nivet, Marie Laure; Poggi, Philippe; Haurant, P; 10.4229/24thEUPVSEC2009-5BV.2.35

    2010-01-01

    The official meteorological network is poor on the island of Corsica: only three sites being about 50 km apart are equipped with pyranometers which enable measurements by hourly and daily step. These sites are Ajaccio (41\\degree 55'N and 8\\degree 48'E, seaside), Bastia (42\\degree 33'N, 9\\degree 29'E, seaside) and Corte (42\\degree 30'N, 9\\degree 15'E average altitude of 486 meters). This lack of weather station makes difficult the predictability of PV power grid performance. This work intends to study a methodology which can predict global solar irradiation using data available from another location for daily and hourly horizon. In order to achieve this prediction, we have used Artificial Neural Network which is a popular artificial intelligence technique in the forecasting domain. A simulator has been obtained using data available for the station of Ajaccio that is the only station for which we have a lot of data: 16 years from 1972 to 1987. Then we have tested the efficiency of this simulator in two places w...

  11. Skin sites to predict deep-body temperature while wearing firefighters' personal protective equipment during periodical changes in air temperature.

    Science.gov (United States)

    Kim, Siyeon; Lee, Joo-Young

    2016-04-01

    The aim of this study was to investigate stable and valid measurement sites of skin temperatures as a non-invasive variable to predict deep-body temperature while wearing firefighters' personal protective equipment (PPE) during air temperature changes. Eight male firefighters participated in an experiment which consisted of 60-min exercise and 10-min recovery while wearing PPE without self-contained breathing apparatus (7.75 kg in total PPE mass). Air temperature was periodically fluctuated from 29.5 to 35.5 °C with an amplitude of 6 °C. Rectal temperature was chosen as a deep-body temperature, and 12 skin temperatures were recorded. The results showed that the forehead and chest were identified as the most valid sites to predict rectal temperature (R(2) = 0.826 and 0.824, respectively) in an environment with periodically fluctuated air temperatures. This study suggests that particular skin temperatures are valid as a non-invasive variable when predicting rectal temperature of an individual wearing PPE in changing ambient temperatures. Practitioner Summary: This study should offer assistance for developing a more reliable indirect indicating system of individual heat strain for firefighters in real time, which can be used practically as a precaution of firefighters' heat-related illness and utilised along with physiological monitoring.

  12. The Predicting Model of E-commerce Site Based on the Ideas of Curve Fitting

    Science.gov (United States)

    Tao, Zhang; Li, Zhang; Dingjun, Chen

    On the basis of the idea of the second multiplication curve fitting, the number and scale of Chinese E-commerce site is analyzed. A preventing increase model is introduced in this paper, and the model parameters are solved by the software of Matlab. The validity of the preventing increase model is confirmed though the numerical experiment. The experimental results show that the precision of preventing increase model is ideal.

  13. Prediction and Analysis of Post-Translational Pyruvoyl Residue Modification Sites from Internal Serines in Proteins

    OpenAIRE

    Jiang, Yang; Li, Bi-Qing; Zhang, Yuchao; Feng, Yuan-Ming; Gao, Yu-Fei; Zhang, Ning; Cai, Yu-Dong

    2013-01-01

    Most of pyruvoyl-dependent proteins observed in prokaryotes and eukaryotes are critical regulatory enzymes, which are primary targets of inhibitors for anti-cancer and anti-parasitic therapy. These proteins undergo an autocatalytic, intramolecular self-cleavage reaction in which a covalently bound pyruvoyl group is generated on a conserved serine residue. Traditional detections of the modified serine sites are performed by experimental approaches, which are often labor-intensive and time-cons...

  14. School Pharmacist/School Environmental Hygienic Activities at School Site.

    Science.gov (United States)

    Muramatsu, Akiyoshi

    2016-01-01

    The "School Health and Safety Act" was enforced in April 2009 in Japan, and "school environmental health standards" were established by the Minister of Education, Culture, Sports, Science and Technology. In Article 24 of the Enforcement Regulations, the duties of the school pharmacist have been clarified; school pharmacists have charged with promoting health activities in schools and carrying out complete and regular checks based on the "school environmental health standards" in order to protect the health of students and staff. In supported of this, the school pharmacist group of Japan Pharmaceutical Association has created and distributed digital video discs (DVDs) on "check methods of school environmental health standards" as support material. We use the DVD to ensure the basic issues that school pharmacists deal with, such as objectives, criteria, and methods for each item to be checked, advice, and post-measures. We conduct various workshops and classes, and set up Q&A committees so that inquiries from members are answered with the help of such activities. In addition, school pharmacists try to improve the knowledge of the school staff on environmental hygiene during their in-service training. They also conduct "drug abuse prevention classes" at school and seek to improve knowledge and recognition of drugs, including "dangerous drugs". PMID:27252053

  15. Predicting long-term moisture contents of earthen covers at uranium mill tailings sites

    International Nuclear Information System (INIS)

    The three methods for long-term moisture prediction covered in this report are: estimates from water retention (permanent wilting point) data, correlation with climate and soil type, and detailed model simulation. The test results have shown: soils vary greatly in residual moisture. Expected long-term moisture saturation ratios (based on generalized soil characteristics) range from 0.2 to 0.8 for soils ranging in texture from sand to clay, respectively. These values hold for noncompacted field soils. Measured radon diffusion coefficients for soils at 15-bar water contents ranged from 5.0E-2 cm2/s to 5.0E-3 cm2/s for sands and clays, respectively, at typical field densities. In contrast, fine-textured pit-run earthen materials, subjected to optimum compaction (>85% Proctor density) and dried to the 15-bar water content, ranged from 0.7 to 0.9 moisture saturation. Compacted pit-run soils at these moisture contents exhibited radon diffusion coefficients as low as 3.0E-4 cm2/s. The residual moisture saturation for cover soils is not known since no engineered barrier has been in place for more than a few years. A comparison of methods for predicting moisture saturation indicates that model simulations are useful for predicting effects of climatic changes on residual soil moisture, but that long-term moisture also can be predicted with some degree of confidence using generalized soil properties or empirical correlations based both on soils and climatic information. The optimal soil cover design will likely include more than one layer of soil. A two-layer system using a thick (1-m minimum) plant root zone of uncompacted soil placed over a moistened, tightly compacted fine-textured soil is recommended. This design concept has been tested successfully at the Grand Junction, Colorado, tailings piles

  16. Predicting long-term moisture contents of earthen covers at uranium mill tailings sites

    Energy Technology Data Exchange (ETDEWEB)

    Gee, G.W.; Nielson, K.K.; Rogers, V.C.

    1984-09-01

    The three methods for long-term moisture prediction covered in this report are: estimates from water retention (permanent wilting point) data, correlation with climate and soil type, and detailed model simulation. The test results have shown: soils vary greatly in residual moisture. Expected long-term moisture saturation ratios (based on generalized soil characteristics) range from 0.2 to 0.8 for soils ranging in texture from sand to clay, respectively. These values hold for noncompacted field soils. Measured radon diffusion coefficients for soils at 15-bar water contents ranged from 5.0E-2 cm/sup 2//s to 5.0E-3 cm/sup 2//s for sands and clays, respectively, at typical field densities. In contrast, fine-textured pit-run earthen materials, subjected to optimum compaction (>85% Proctor density) and dried to the 15-bar water content, ranged from 0.7 to 0.9 moisture saturation. Compacted pit-run soils at these moisture contents exhibited radon diffusion coefficients as low as 3.0E-4 cm/sup 2//s. The residual moisture saturation for cover soils is not known since no engineered barrier has been in place for more than a few years. A comparison of methods for predicting moisture saturation indicates that model simulations are useful for predicting effects of climatic changes on residual soil moisture, but that long-term moisture also can be predicted with some degree of confidence using generalized soil properties or empirical correlations based both on soils and climatic information. The optimal soil cover design will likely include more than one layer of soil. A two-layer system using a thick (1-m minimum) plant root zone of uncompacted soil placed over a moistened, tightly compacted fine-textured soil is recommended. This design concept has been tested successfully at the Grand Junction, Colorado, tailings piles.

  17. Nonlinear Economic Model Predictive Control Strategy for Active Smart Buildings

    DEFF Research Database (Denmark)

    Santos, Rui Mirra; Zong, Yi; Sousa, Joao M. C.;

    2016-01-01

    Nowadays, the development of advanced and innovative intelligent control techniques for energy management in buildings is a key issue within the smart grid topic. A nonlinear economic model predictive control (EMPC) scheme, based on the branch-and-bound tree search used as optimization algorithm...... for solving the nonconvex optimization problem is proposed in this paper. A simulation using the nonlinear model-based controller to control the temperature levels of an intelligent office building (PowerFlexHouse) is addressed. Its performance is compared with a linear model-based controller. The nonlinear...

  18. Transfer Student Success: Educationally Purposeful Activities Predictive of Undergraduate GPA

    Science.gov (United States)

    Fauria, Renee M.; Fuller, Matthew B.

    2015-01-01

    Researchers evaluated the effects of Educationally Purposeful Activities (EPAs) on transfer and nontransfer students' cumulative GPAs. Hierarchical, linear, and multiple regression models yielded seven statistically significant educationally purposeful items that influenced undergraduate student GPAs. Statistically significant positive EPAs for…

  19. A PBPK Model to Predict Disposition of CYP3A-Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction.

    Science.gov (United States)

    Ke, A B; Nallani, S C; Zhao, P; Rostami-Hodjegan, A; Unadkat, J D

    2012-01-01

    Besides logistical and ethical concerns, evaluation of safety and efficacy of medications in pregnant women is complicated by marked changes in pharmacokinetics (PK) of drugs. For example, CYP3A activity is induced during the third trimester (T3). We explored whether a previously published physiologically based pharmacokinetic (PBPK) model could quantitatively predict PK profiles of CYP3A-metabolized drugs during T3, and discern the site of CYP3A induction (i.e., liver, intestine, or both). The model accounted for gestational age-dependent changes in maternal physiological function and hepatic CYP3A activity. For model verification, mean plasma area under the curve (AUC), peak plasma concentration (Cmax), and trough plasma concentration (Cmin) of midazolam (MDZ), nifedipine (NIF), and indinavir (IDV) were predicted and compared with published studies. The PBPK model successfully predicted MDZ, NIF, and IDV disposition during T3. A sensitivity analysis suggested that CYP3A induction in T3 is most likely hepatic and not intestinal. Our PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e3; doi:10.1038/psp.2012.2; advance online publication 26 September 2012. PMID:23835883

  20. Anxiety symptoms and disorder predict activity limitations in the elderly.

    OpenAIRE

    Norton, Joanna; Ancelin, Marie-Laure; Stewart, Rob; BERR, Claudine; Ritchie, Karen; Carrière, Isabelle

    2012-01-01

    International audience BACKGROUND: In the elderly, little attention has been paid to anxiety both on a symptom dimension and as a disorder, as an independent risk factor for the incidence of activity limitations. METHODS: In a community-dwelling cohort of 1581 persons aged 65+, the association between trait anxiety symptoms (Spielberger Trait, third highest tertile) and baseline DSM-IV anxiety disorder, and 7-year incident activity limitations was determined using mixed logistic regression...

  1. Isolated metal active site concentration and stability control catalytic CO2 reduction selectivity.

    Science.gov (United States)

    Matsubu, John C; Yang, Vanessa N; Christopher, Phillip

    2015-03-01

    CO2 reduction by H2 on heterogeneous catalysts is an important class of reactions that has been studied for decades. However, atomic scale details of structure-function relationships are still poorly understood. Particularly, it has been suggested that metal particle size plays a unique role in controlling the stability of CO2 hydrogenation catalysts and the distribution of active sites, which dictates reactivity and selectivity. These studies often have not considered the possible role of isolated metal active sites in the observed dependences. Here, we utilize probe molecule diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) with known site-specific extinction coefficients to quantify the fraction of Rh sites residing as atomically dispersed isolated sites (Rhiso), as well as Rh sites on the surface of Rh nanoparticles (RhNP) for a series of TiO2 supported Rh catalysts. Strong correlations were observed between the catalytic reverse water gas shift turn over frequency (TOF) and the fraction of Rhiso sites and between catalytic methanation TOF and the fraction of RhNP sites. Furthermore, it was observed that reaction condition-induced disintegration of Rh nanoparticles, forming Rhiso active sites, controls the changing reactivity with time on stream. This work demonstrates that isolated atoms and nanoparticles of the same metal on the same support can exhibit uniquely different catalytic selectivity in competing parallel reaction pathways and that disintegration of nanoparticles under reaction conditions can play a significant role in controlling stability. PMID:25671686

  2. A predictive control algorithm for an active three-phase power filter

    Directory of Open Access Journals (Sweden)

    R.V. Vlasenko

    2014-09-01

    Full Text Available The paper deals with grid connection circuits for active filters, structures of active power filter control systems, and methods based on full capacity components determination. The existing structures of active power filter control and control algorithm adjustment for valve commutation loss reduction are analyzed. A predictive control algorithm for an active three-phase power filter is introduced.

  3. A predictive control algorithm for an active three-phase power filter

    OpenAIRE

    R.V. Vlasenko; Bialobrzeski, O. V.

    2014-01-01

    The paper deals with grid connection circuits for active filters, structures of active power filter control systems, and methods based on full capacity components determination. The existing structures of active power filter control and control algorithm adjustment for valve commutation loss reduction are analyzed. A predictive control algorithm for an active three-phase power filter is introduced.

  4. 77 FR 74218 - Commercial Wind Leasing and Site Assessment Activities on the Atlantic Outer Continental Shelf...

    Science.gov (United States)

    2012-12-13

    ... published a Notice of Availability (NOA) in the Federal Register (72 FR 62,672) of the Programmatic EIS for... Federal Register (77 FR 5560) of the Final EA for Commercial Wind Lease Issuance and Site Assessment... Bureau of Ocean Energy Management Commercial Wind Leasing and Site Assessment Activities on the...

  5. 75 FR 71677 - Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites

    Science.gov (United States)

    2010-11-24

    ... Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites AGENCY: Department of... uranium and thorium processing site licensees for reimbursement under Title X of the Energy Policy Act of... requires DOE to reimburse eligible uranium and thorium licensees for certain costs of...

  6. 77 FR 3460 - Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites

    Science.gov (United States)

    2012-01-24

    ... Reimbursement for Costs of Remedial Action at Active Uranium and Thorium Processing Sites AGENCY: Department of... uranium and thorium processing site licensees for reimbursement under Title X of the Energy Policy Act of... requires DOE to reimburse eligible uranium and thorium licensees for certain costs of...

  7. 1993 annual report of hazardous waste activities for the Oak Ridge K-25 site

    Energy Technology Data Exchange (ETDEWEB)

    1994-02-01

    This report is a detailed listing of all of the Hazardous Waste activities occurring at Martin Marietta`s K-25 site. Contained herein are hazardous waste notification forms, waste stream reports, generator fee forms and various TSDR reports.

  8. Poisoning Experiments Aimed at Discriminating Active and Less-Active Sites of Silica-Supported Tantalum Hydride for Alkane Metathesis

    KAUST Repository

    Saggio, Guillaume

    2010-10-04

    Only 50% of the silica-supported tantalum hydride sites are active in the metathesis of propane. Indeed, more than 45% of the tantalum hydride can be eliminated by a selective oxygen poisoning of inactive sites with no significant decrease in the global turnover. Conversely, cyclopentane induces no such selective poisoning. Hence, the active tantalum hydride sites that show greater resistance to oxygen poisoning correspond to the νTa-H bands of higher wavenumbers, particularly that at 1860cm-1. These active tantalum hydride sites should correspond to tris- or monohydride species relatively far from silica surface oxygen atoms. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Surface properties of the Mars Science Laboratory candidate landing sites: characterization from orbit and predictions

    Science.gov (United States)

    Fergason, R.L.; Christensen, P.R.; Golombek, M.P.; Parker, T.J.

    2012-01-01

    This work describes the interpretation of THEMIS-derived thermal inertia data at the Eberswalde, Gale, Holden, and Mawrth Vallis Mars Science Laboratory (MSL) candidate landing sites and determines how thermophysical variations correspond to morphology and, when apparent, mineralogical diversity. At Eberswalde, the proportion of likely unconsolidated material relative to exposed bedrock or highly indurated surfaces controls the thermal inertia of a given region. At Gale, the majority of the landing site region has a moderate thermal inertia (250 to 410 J m-2 K-1 s-1/2), which is likely an indurated surface mixed with unconsolidated materials. The primary difference between higher and moderate thermal inertia surfaces may be due to the amount of mantling material present. Within the mound of stratified material in Gale, layers are distinguished in the thermal inertia data; the MSL rover could be traversing through materials that are both thermophysically and compositionally diverse. The majority of the Holden ellipse has a thermal inertia of 340 to 475 J m-2 K-1 s-1/2 and consists of bed forms with some consolidated material intermixed. Mawrth Vallis has a mean thermal inertia of 310 J m-2 K-1 s-1/2 and a wide variety of materials is present contributing to the moderate thermal inertia surfaces, including a mixture of bedrock, indurated surfaces, bed forms, and unconsolidated fines. Phyllosilicates have been identified at all four candidate landing sites, and these clay-bearing units typically have a similar thermal inertia value (400 to 500 J m-2 K-1 s-1/2), suggesting physical properties that are also similar.

  10. On the nature of Parr functions to predict the most reactive sites along organic polar reactions

    Science.gov (United States)

    Chamorro, Eduardo; Pérez, Patricia; Domingo, Luis R.

    2013-09-01

    Very recently, local electrophilic and nucleophilic “Parr functions” were empirically introduced (L.R. Domingo, P. Pérez, J.A. Saez RSC Adv. 3 (2013) 1486) in order to properly characterize the most reactive sites along polar chemical reactions. This Letter reports a theoretical advance to the new methodology by identifying these quantities with key Fukui descriptors of the spin-polarized density functional theory. Given such framework properly incorporates the treatment of both charge-transfer and spin-polarization, this finding provides a significant insight and substantial step forward within the field of a chemical reactivity theory based on the conceptual framework of density functional theory.

  11. Improved Computational Target Site Prediction for Pentatricopeptide Repeat RNA Editing Factors

    OpenAIRE

    TAKENAKA, MIZUKI; Zehrmann, Anja; Brennicke, Axel; Graichen, Knut

    2013-01-01

    Pentatricopeptide repeat (PPR) proteins with an E domain have been identified as specific factors for C to U RNA editing in plant organelles. These PPR proteins bind to a unique sequence motif 5′ of their target editing sites. Recently, involvement of a combinatorial amino acid code in the P (normal length) and S type (short) PPR domains in sequence specific RNA binding was reported. PPR proteins involved in RNA editing, however, contain not only P and S motifs but also their long variants L ...

  12. Type 2 diabetes mellitus: phylogenetic motifs for predicting protein functional sites

    Indian Academy of Sciences (India)

    Ashok Sharma; Tanuja Rastogi; Meenakshi Bhartiya; A K Shasany; S P S Khanuja

    2007-08-01

    Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites. In this article, we have identified PMs for all the candidate genes for type 2 diabetes mellitus. Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11. Isoleucine 137 was conserved for insulin receptor and regulatory subunit of a phosphorylating enzyme. Whereas residues valine, leucine, methionine were highly conserved for insulin receptor. Occurrence of proline was very high for calpain 10 gene and glucose transporter

  13. Coordination environment of the active-site metal ion of liver alcohol dehydrogenase.

    OpenAIRE

    Makinen, M W; Yim, M B

    1981-01-01

    The coordination environment of the catalytically active metal ion of horse liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) has been investigated by electron paramagnetic resonance (EPR) methods with use of the active-site-specific Co2+-reconstituted enzyme. The EPR absorption spectrum of the metal-substituted enzyme is characteristic of a rhombically distorted environment. The spectrum of the enzyme--NAD+ complex shows approximate axial symmetry of the metal ion site, i...

  14. Denaturation studies of active-site labeled papain using electron paramagnetic resonance and fluorescence spectroscopy.

    OpenAIRE

    Ping, Z A; Butterfiel, D A

    1991-01-01

    A spin-labeled p-chloromercuribenzoate (SL-PMB) and a fluorescence probe, 6-acryloyl-2-dimethylaminonaphthalene (Acrylodan), both of which bind to the single SH group located in the active site of papain, were used to investigate the interaction of papain (EC 3.4.22.2) with two protein denaturants. It was found that the active site of papain was highly stable in urea solution, but underwent a large conformational change in guanidine hydrochloride solution. Electron paramagnetic resonance and ...

  15. Complement receptor 2–mediated targeting of complement inhibitors to sites of complement activation

    OpenAIRE

    Song, Hongbin; He, Chun; Knaak, Christian; GUTHRIDGE, JOEL M.; Holers, V. Michael; Tomlinson, Stephen

    2003-01-01

    In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the mem...

  16. The thermal stability of the framework, hydroxyl groups, and active sites of faujasites

    Energy Technology Data Exchange (ETDEWEB)

    Mishin, I.V.; Kalinin, V.P.; Nissenbaum, V.D. [Zelinskii Institute of Organic Chemistry, Moscow (Russian Federation); Beyer, H.K. [Hungarian Academy of Sciences, Budapest (Hungary); Karge, H.G. [Fritz Haber Institute of the Max Planck Soceity, Berlin (Germany)

    1994-07-01

    The effect of the framework composition on the crystallinity and {open_quotes}density{close_quotes} of hydroxyl groups and the concentration of active sites is reported for hydrogen forms of Y zeolites preheated at 400 - 1000{degrees}C. The increase in the Si/Al ratios results in improved resistance of the framework atoms and hydroxyl groups to high temperatures and in enhanced thermal stability of the sites that are active in the cracking of isooctane and disproportionation of ethylbenzene.

  17. Active site dynamics of toluene hydroxylation by cytochrome P-450

    International Nuclear Information System (INIS)

    Rat liver cytochrome P-450 hydroxylates toluene to benzyl alcohol plus o-, m-, and p-cresol. Deuterated toluenes were incubated under saturating conditions with liver microsomes from phenobarbital-pretreated rats, and product yields and ratios were measured. Stepwise deuteration of the methyl leads to stepwise decreases in the alcohol/cresol ratio without changing the cresol isomer ratios. Extensive deuterium retention in the benzyl alcohols from PhCH2D and PhCHD2 suggests there is a large intrinsic isotope effect for benzylic hydroxylation. After replacement of the third benzylic H by D, the drop in the alcohol/cresol ratio was particularly acute, suggsting that metabolic switching from D to H within the methyl group was easier than switching from the methyl to the ring. Comparison of the alcohol/cresol ratio for PhCH3 vs PhCD3 indicated a net isotope effect of 6.9 for benzylic hydroxylation. From product yield data for PhCH3 and PhCD3, DV for benzyl alcohol formation is only 1.92, whereas DV for total product formation is 0.67 (i.e., inverse). From competitive incubations of PhCH3/PhCD3 mixtures D(V/K) isotope effects on benzyl alcohol formation and total product formation (3.6 and 1.23, respectively) are greatly reduced, implying strong commitment to catalysis. In contrast, D(V/K) for the alcohol/cresol ratio is 6.3, indicating that the majority of the intrinsic isotope effect is expressed through metabolic switching. Overall, these data are consistent with reversible formation of a complex between toluene and the active oxygen form of cytochrome P-450, which rearranges internally and reacts to form products faster than it dissociates back to release substrate

  18. The Predictive Role of Stock Market Return for Real Activity in Thailand

    OpenAIRE

    Jiranyakul, Komain

    2012-01-01

    Stock market return is one of financial variables that contain information to forecast real activity such as industrial production and real GDP growth. However, it is still controversial that stock market return can have a predictive content on real activity. This paper attempts to investigate the ability of stock market return to predict industrial production growth (or real activity) in Thailand, which is an emerging market economy. The standard causality test and the equal forecast evalua...

  19. The complexities of measuring access to parks and physical activity sites in New York City: a quantitative and qualitative approach

    Directory of Open Access Journals (Sweden)

    Sohler Nancy L

    2009-06-01

    Full Text Available Abstract Background Proximity to parks and physical activity sites has been linked to an increase in active behaviors, and positive impacts on health outcomes such as lower rates of cardiovascular disease, diabetes, and obesity. Since populations with a low socio-economic status as well as racial and ethnic minorities tend to experience worse health outcomes in the USA, access to parks and physical activity sites may be an environmental justice issue. Geographic Information systems were used to conduct quantitative and qualitative analyses of park accessibility in New York City, which included kernel density estimation, ordinary least squares (global regression, geographically weighted (local regression, and longitudinal case studies, consisting of field work and archival research. Accessibility was measured by both density of park acreage and density of physical activity sites. Independent variables included percent non-Hispanic black, percent Hispanic, percent below poverty, percent of adults without high school diploma, percent with limited English-speaking ability, and population density. Results The ordinary least squares linear regression found weak relationships in both the park acreage density and the physical activity site density models (Ra2 = .11 and .23, respectively; AIC = 7162 and 3529, respectively. Geographically weighted regression, however, suggested spatial non-stationarity in both models, indicating disparities in accessibility that vary over space with respect to magnitude and directionality of the relationships (AIC = 2014 and -1241, respectively. The qualitative analysis supported the findings of the local regression, confirming that although there is a geographically inequitable distribution of park space and physical activity sites, it is not globally predicted by race, ethnicity, or socio-economic status. Conclusion The combination of quantitative and qualitative analyses demonstrated the complexity of the issues around

  20. Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

    NARCIS (Netherlands)

    de Sousa Pereira Simoes de Melo, Manuel; Ferre, Rafael; Feliu, Lidia; Bardaji, Eduard; Planas, Marta; Castanho, Miguel A. R. B.

    2011-01-01

    Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible co

  1. Predicting and preventing the future: actively managing multiple sclerosis.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    Relapsing-remitting multiple sclerosis (MS) has a highly variable clinical course but a number of demographic, clinical and MRI features can guide the clinician in the assessment of disease activity and likely disability outcome. It is also clear that the inflammatory activity in the first five years of relapsing-remitting MS results in the neurodegenerative changes seen in secondary progressive MS 10-15 years later. While conventional first-line disease modifying therapy has an effect on relapses, about one third of patients have a suboptimal response to treatment. With the advent of highly active second-line therapies with their evident marked suppression of inflammation, the clinician now has the tools to manage the course of relapsing-remitting MS more effectively. The development of treatment optimisation recommendations based on the clinical response to first-line therapies can guide the neurologist in more active management of the early course of relapsing-remitting MS, with the aim of preventing both acute inflammatory axonal injury and the neurodegenerative process which leads to secondary progressive MS.

  2. Predicting Nitrogen Fertilizer Recommendations for Corn using an Active Sensor

    Science.gov (United States)

    Active sensors, mounted on typical agricultural equipment, can be used to measure N (nitrogen) status in corn (Zea mays L.). This gives a producer the potential to improve N fertilizer recommendations that will reduce nitrate loss to the environment. This study examines the relationship between re...

  3. 'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

    Science.gov (United States)

    Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

    2014-04-01

    The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

  4. 'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

    Science.gov (United States)

    Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

    2014-04-01

    The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins. PMID:24635441

  5. Active sites for NO reduction over Fe-ZSM-5 catalysts.

    Science.gov (United States)

    Schwidder, M; Santhosh Kumar, M; Brückner, A; Grünert, W

    2005-02-14

    A study of Fe-ZSM-5 catalysts with variable amounts of isolated, oligomeric and heavily aggregated Fe3+ oxo sites (as evidenced by UV-Vis and EPR spectroscopic data) and their catalytic properties in the selective catalytic reduction of NO by isobutane or by NH3 is presented, which allows development of a unified concept of the active Fe sites in these reactions, according to which isolated Fe sites catalyse both SCR reactions while oligomeric sites, though also involved in the selective reduction path, limit the catalyst performance by causing the total oxidation of the reductant. PMID:15685345

  6. Benzene Hydroxylation over FeZSM-5 Catalysts: Which Fe-sites Are Active?

    OpenAIRE

    Yuranov, I.; Bulushev, D. A.; Renken, A.; Kiwi-Minsker, L.

    2004-01-01

    FeZSM-5 with a wide range of Fe content (0.015–2.1 wt%) were studied in the benzene hydroxylation to phenol with nitrous oxide (C6H6:N2O = 1:5) at low temperatures (98%) was obtained within 3 h without any deactivation of the catalyst. Three types of Fe(II) sites were formed in the zeolites extraframework due to activation and are attributed to: (1) Fe(II) sites in mononuclear species, (2) oligonuclear species with at least two oxygen-bridged Fe(II) sites, and (3) Fe(II) sites within Fe2O3 na...

  7. XAFS Study of the Photo-Active Site of Mo/MCM-41

    International Nuclear Information System (INIS)

    An Mo/MCM-41 catalyst was prepared and used for study of propene and 1-butene photo-metathesis reactions. XAFS analysis revealed that hydrogen reduction leads to a decreased role for the Mo=O site. The Mo-O site plays an important role for the olefin photo-metathesis reaction on the H2 reduced Mo/MCM-41. From EXAFS analysis, the active site of photo-metathesis reaction is the Mo=O part for oxidized Mo/MCM-41, whereas it is the Mo-O site for reduced Mo/MCM-41

  8. XAFS Study of the Photo-Active Site of Mo/MCM-41

    Science.gov (United States)

    Miyamoto, Daisuke; Ichikuni, Nobuyuki; Shimazu, Shogo

    2007-02-01

    An Mo/MCM-41 catalyst was prepared and used for study of propene and 1-butene photo-metathesis reactions. XAFS analysis revealed that hydrogen reduction leads to a decreased role for the Mo=O site. The Mo-O site plays an important role for the olefin photo-metathesis reaction on the H2 reduced Mo/MCM-41. From EXAFS analysis, the active site of photo-metathesis reaction is the Mo=O part for oxidized Mo/MCM-41, whereas it is the Mo-O site for reduced Mo/MCM-41.

  9. Predicting mixed-gas adsorption equilibria on activated carbon for precombustion CO2 capture.

    Science.gov (United States)

    García, S; Pis, J J; Rubiera, F; Pevida, C

    2013-05-21

    We present experimentally measured adsorption isotherms of CO2, H2, and N2 on a phenol-formaldehyde resin-based activated carbon, which had been previously synthesized for the separation of CO2 in a precombustion capture process. The single component adsorption isotherms were measured in a magnetic suspension balance at three different temperatures (298, 318, and 338 K) and over a large range of pressures (from 0 to 3000-4000 kPa). These values cover the temperature and pressure conditions likely to be found in a precombustion capture scenario, where CO2 needs to be separated from a CO2/H2/N2 gas stream at high pressure (~1000-1500 kPa) and with a high CO2 concentration (~20-40 vol %). Data on the pure component isotherms were correlated using the Langmuir, Sips, and dual-site Langmuir (DSL) models, i.e., a two-, three-, and four-parameter model, respectively. By using the pure component isotherm fitting parameters, adsorption equilibrium was then predicted for multicomponent gas mixtures by the extended models. The DSL model was formulated considering the energetic site-matching concept, recently addressed in the literature. Experimental gas-mixture adsorption equilibrium data were calculated from breakthrough experiments conducted in a lab-scale fixed-bed reactor and compared with the predictions from the models. Breakthrough experiments were carried out at a temperature of 318 K and five different pressures (300, 500, 1000, 1500, and 2000 kPa) where two different CO2/H2/N2 gas mixtures were used as the feed gas in the adsorption step. The DSL model was found to be the one that most accurately predicted the CO2 adsorption equilibrium in the multicomponent mixture. The results presented in this work highlight the importance of performing experimental measurements of mixture adsorption equilibria, as they are of utmost importance to discriminate between models and to correctly select the one that most closely reflects the actual process.

  10. The utility of geometrical and chemical restraint information extracted from predicted ligand-binding sites in protein structure refinement.

    Science.gov (United States)

    Brylinski, Michal; Lee, Seung Yup; Zhou, Hongyi; Skolnick, Jeffrey

    2011-03-01

    Exhaustive exploration of molecular interactions at the level of complete proteomes requires efficient and reliable computational approaches to protein function inference. Ligand docking and ranking techniques show considerable promise in their ability to quantify the interactions between proteins and small molecules. Despite the advances in the development of docking approaches and scoring functions, the genome-wide application of many ligand docking/screening algorithms is limited by the quality of the binding sites in theoretical receptor models constructed by protein structure prediction. In this study, we describe a new template-based method for the local refinement of ligand-binding regions in protein models using remotely related templates identified by threading. We designed a Support Vector Regression (SVR) model that selects correct binding site geometries in a large ensemble of multiple receptor conformations. The SVR model employs several scoring functions that impose geometrical restraints on the Cα positions, account for the specific chemical environment within a binding site and optimize the interactions with putative ligands. The SVR score is well correlated with the RMSD from the native structure; in 47% (70%) of the cases, the Pearson's correlation coefficient is >0.5 (>0.3). When applied to weakly homologous models, the average heavy atom, local RMSD from the native structure of the top-ranked (best of top five) binding site geometries is 3.1Å (2.9Å) for roughly half of the targets; this represents a 0.1 (0.3)Å average improvement over the original predicted structure. Focusing on the subset of strongly conserved residues, the average heavy atom RMSD is 2.6Å (2.3Å). Furthermore, we estimate the upper bound of template-based binding site refinement using only weakly related proteins to be ∼2.6Å RMSD. This value also corresponds to the plasticity of the ligand-binding regions in distant homologues. The Binding Site Refinement (BSR

  11. Understanding Land-Atmosphere Coupling and its Predictability at the ARM Southern Great Plains Site

    Science.gov (United States)

    Ferguson, C. R.; Song, H. J.; Roundy, J. K.

    2015-12-01

    Ten years ago, the Global Energy and Water EXchanges Global Land Atmosphere Coupling Experiment (GLACE) spotlighted the Southern Great Plains (SGP) for being one of three hotspots globally for land-derived precipitation predictability. Since then, the GLACE results have served as the underlying motivation for numerous subsequent land-atmosphere (L-A) coupling studies over the SGP domain. The range of these studies includes: local point scale studies leveraging surface meteorological and flux measurements at the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement SGP (ARM-SGP) Central Facility, regional pentad to monthly scale atmospheric moisture budget analyses based on atmospheric reanalysis, and regional limited duration (2-7 day) coupled model sensitivity experiments. This study has the following three objectives: (1) to provide the common historical context necessary for bridging past and future interdisciplinary characterizations of L-A coupling, (2) to isolate the mechanism(s) for the region's L-A coupling signal, and (3) to evaluate the short range (12-18hr) predictability of soil moisture-precipitation feedbacks. We produce a convective triggering potential—low-level humidity index (CTP-HI)—based climatology of L-A coupling at ARM-SGP for the period 1979-2014 using North American Regional Reanalysis and North American Land Data Assimilation System Phase 2 data. We link the underlying coupling regime classification timeseries to corresponding synoptic-mesoscale weather patterns and bulk atmospheric moisture budget analyses. On the whole, the region's precipitation variability is largely dependent on large-scale moisture transport and the role of the land is nominal. However, we show that surface sensible heat flux can play an important role in modulating diurnal precipitation cycle phase and amplitude—either directly (enhancing CTP) in water-limited conditions or indirectly (increasing HI) in energy-limited conditions. In fact, both 0700

  12. Concept for calculating dose rates from activated groundwater at accelerator sites

    CERN Document Server

    Prolingheuer, N; Vanderborght, J; Schlögl, B; Nabbi, R; Moormann, R

    Licensing of particle accelerators requires the proof that the groundwater outside of the site will not be significantly contaminated by activation products formed below accelerator and target. In order to reduce the effort for this proof, a site independent simplified but conservative method is under development. The conventional approach for calculation of activation of soil and groundwater is shortly described on example of a site close to Forschungszentrum Juelich, Germany. Additionally an updated overview of a data library for partition coefficients for relevant nuclides transported in the aquifer at the site is presented. The approximate model for transport of nuclides with ground water including exemplary results on nuclide concentrations outside of the site boundary and of resulting effective doses is described. Further applications and developments are finally outlined.

  13. Molecular physicochemical parameters predicting antioxidant activity of Brazilian natural products

    Directory of Open Access Journals (Sweden)

    Luciana Scotti

    2009-12-01

    Full Text Available Reactive oxygen species (ROS are capable of oxidizing cellular proteins, nucleic acids and lipids, contributing to cellular aging, mutagenesis, carcinogenesis, coronary heart and neurodegenerative diseases. Free radicals-scavenging by phenolic compounds occurs by the transfer of one electron followed by the H-abstraction. In order to evaluate the antioxidant activity of a series of seventeen phenolic compounds extracted from Brazilian flora (Chimarrhis turbinata and Arrabidea samydoides, some physicochemical parameters (heat formation of the neutral, radical, and cationic compounds; orbitals' energies; ClogP; ΔH OX; and ΔHf were calculated. Considering the results from the calculated descriptors, the molecules 10a-f can be classified as having a higher antioxidant activity.

  14. Baseline brain activity fluctuations predict somatosensory perception in humans

    OpenAIRE

    Boly, M; Balteau, E.; Schnakers, C; Degueldre, C.; Moonen, G.; Luxen, A.; Phillips, C.; Peigneux, P; Maquet, P; Laureys, S.

    2007-01-01

    In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium–yttrium/aluminum–garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity so...

  15. Optimal Coding Predicts Attentional Modulation of Activity in Neural Systems

    OpenAIRE

    Jaramillo, Santiago; Pearlmutter, Barak A.

    2007-01-01

    Neuronal activity in response to a fixed stimulus has been shown to change as a function of attentional state, implying that the neural code also changes with attention. We propose an information-theoretic account of such modulation: that the nervous system adapts to optimally encode sensory stimuli while taking into account the changing relevance of different features. We show using computer simulation that such modulation emerges in a coding system informed about the uneven relevance of ...

  16. TH-A-9A-01: Active Optical Flow Model: Predicting Voxel-Level Dose Prediction in Spine SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Liu, J; Wu, Q.J.; Yin, F; Kirkpatrick, J; Cabrera, A [Duke University Medical Center, Durham, NC (United States); Ge, Y [University of North Carolina at Charlotte, Charlotte, NC (United States)

    2014-06-15

    Purpose: To predict voxel-level dose distribution and enable effective evaluation of cord dose sparing in spine SBRT. Methods: We present an active optical flow model (AOFM) to statistically describe cord dose variations and train a predictive model to represent correlations between AOFM and PTV contours. Thirty clinically accepted spine SBRT plans are evenly divided into training and testing datasets. The development of predictive model consists of 1) collecting a sequence of dose maps including PTV and OAR (spinal cord) as well as a set of associated PTV contours adjacent to OAR from the training dataset, 2) classifying data into five groups based on PTV's locations relative to OAR, two “Top”s, “Left”, “Right”, and “Bottom”, 3) randomly selecting a dose map as the reference in each group and applying rigid registration and optical flow deformation to match all other maps to the reference, 4) building AOFM by importing optical flow vectors and dose values into the principal component analysis (PCA), 5) applying another PCA to features of PTV and OAR contours to generate an active shape model (ASM), and 6) computing a linear regression model of correlations between AOFM and ASM.When predicting dose distribution of a new case in the testing dataset, the PTV is first assigned to a group based on its contour characteristics. Contour features are then transformed into ASM's principal coordinates of the selected group. Finally, voxel-level dose distribution is determined by mapping from the ASM space to the AOFM space using the predictive model. Results: The DVHs predicted by the AOFM-based model and those in clinical plans are comparable in training and testing datasets. At 2% volume the dose difference between predicted and clinical plans is 4.2±4.4% and 3.3±3.5% in the training and testing datasets, respectively. Conclusion: The AOFM is effective in predicting voxel-level dose distribution for spine SBRT. Partially supported by NIH

  17. Tritium monitoring in groundwater and evaluation of model predictions for the Hanford Site 200 Area Effluent Treatment Facility

    International Nuclear Information System (INIS)

    The Effluent Treatment Facility (ETF) disposal site, also known as the State-Approved Land Disposal Site (SALDS), receives treated effluent containing tritium, which is allowed to infiltrate through the soil column to the water table. Tritium was first detected in groundwater monitoring wells around the facility in July 1996. The SALDS groundwater monitoring plan requires revision of a predictive groundwater model and reevaluation of the monitoring well network one year from the first detection of tritium in groundwater. This document is written primarily to satisfy these requirements and to report on analytical results for tritium in the SALDS groundwater monitoring network through April 1997. The document also recommends an approach to continued groundwater monitoring for tritium at the SALDS. Comparison of numerical groundwater models applied over the last several years indicate that earlier predictions, which show tritium from the SALDS approaching the Columbia River, were too simplified or overly robust in source assumptions. The most recent modeling indicates that concentrations of tritium above 500 pCi/L will extend, at most, no further than ∼1.5 km from the facility, using the most reasonable projections of ETF operation. This extent encompasses only the wells in the current SALDS tritium-tracking network

  18. Computational Characterization and Prediction of Estrogen Receptor Coactivator Binding Site Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, B J; Kulp, K S; Cosman, M; Lightstone, F C

    2005-08-26

    Many carcinogens have been shown to cause tissue specific tumors in animal models. The mechanism for this specificity has not been fully elucidated and is usually attributed to differences in organ metabolism. For heterocyclic amines, potent carcinogens that are formed in well-done meat, the ability to either bind to the estrogen receptor and activate or inhibit an estrogenic response will have a major impact on carcinogenicity. Here we describe our work with the human estrogen receptor alpha (hERa) and the mutagenic/carcinogenic heterocyclic amines PhIP, MeIQx, IFP, and the hydroxylated metabolite of PhIP, N2-hydroxy-PhIP. We found that PhIP, in contrast to the other heterocyclic amines, increased cell-proliferation in MCF-7 human breast cancer cells and activated the hERa receptor. We show mechanistic data supporting this activation both computationally by homology modeling and docking, and by NMR confirmation that PhIP binds with the ligand binding domain (LBD). This binding competes with estradiol (E2) in the native E2 binding cavity of the receptor. We also find that other heterocyclic amines and N2-hydroxy-PhIP inhibit ER activation presumably by binding into another cavity on the LBD. Moreover, molecular dynamics simulations of inhibitory heterocyclic amines reveal a disruption of the surface of the receptor protein involved with protein-protein signaling. We therefore propose that the mechanism for the tissue specific carcinogenicity seen in the rat breast tumors and the presumptive human breast cancer associated with the consumption of well-done meat maybe mediated by this receptor activation.

  19. Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes

    DEFF Research Database (Denmark)

    Cockburn, Darrell; Wilkens, Casper; Dilokpimol, Adiphol;

    2016-01-01

    Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical...... for the activity of their cognate enzyme, though they are not readily detected in the sequence of a protein, but normally require a crystal structure of a complex for their identification. A variety of methods, including affinity electrophoresis (AE), insoluble polysaccharide pulldown (IPP) and surface plasmon...... resonance (SPR) have been used to study auxiliary binding sites. These techniques are complementary as AE allows monitoring of binding to soluble polysaccharides, IPP to insoluble polysaccharides and SPR to oligosaccharides. Here we show that these methods are useful not only for analyzing known binding...

  20. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Crichlow, G.; Lubetsky, J; Leng, L; Bucala, R; Lolis, E

    2009-01-01

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.

  1. Predicting activities without computing descriptors: graph machines for QSAR.

    Science.gov (United States)

    Goulon, A; Picot, T; Duprat, A; Dreyfus, G

    2007-01-01

    We describe graph machines, an alternative approach to traditional machine-learning-based QSAR, which circumvents the problem of designing, computing and selecting molecular descriptors. In that approach, which is similar in spirit to recursive networks, molecules are considered as structured data, represented as graphs. For each example of the data set, a mathematical function (graph machine) is built, whose structure reflects the structure of the molecule under consideration; it is the combination of identical parameterised functions, called "node functions" (e.g. a feedforward neural network). The parameters of the node functions, shared both within and across the graph machines, are adjusted during training with the "shared weights" technique. Model selection is then performed by traditional cross-validation. Therefore, the designer's main task consists in finding the optimal complexity for the node function. The efficiency of this new approach has been demonstrated in many QSAR or QSPR tasks, as well as in modelling the activities of complex chemicals (e.g. the toxicity of a family of phenols or the anti-HIV activities of HEPT derivatives). It generally outperforms traditional techniques without requiring the selection and computation of descriptors. PMID:17365965

  2. Computational prediction of cAMP receptor protein (CRP) binding sites in cyanobacterial genomes

    OpenAIRE

    Su Zhengchang; Xu Minli

    2009-01-01

    Abstract Background Cyclic AMP receptor protein (CRP), also known as catabolite gene activator protein (CAP), is an important transcriptional regulator widely distributed in many bacteria. The biological processes under the regulation of CRP are highly diverse among different groups of bacterial species. Elucidation of CRP regulons in cyanobacteria will further our understanding of the physiology and ecology of this important group of microorganisms. Previously, CRP has been experimentally st...

  3. Directed Hierarchical Patterning of Polycarbonate Bisphenol A Glass Surface along Predictable Sites

    Directory of Open Access Journals (Sweden)

    Mazen Khaled

    2015-01-01

    Full Text Available This paper reports a new approach in designing textured and hierarchical surfaces on polycarbonate bisphenol A type glass to improve hydrophobicity and dust repellent application for solar panels. Solvent- and vapor-induced crystallization of thermoplastic glass polycarbonate bisphenol A (PC is carried out to create hierarchically structured surfaces. In this approach dichloromethane (DCM and acetone are used in sequence. Samples are initially immersed in DCM liquid to generate nanopores, followed by exposing to acetone vapor resulting in the generation of hierarchical structure along the interporous sites. The effects of exposure time on the size, density, and distance of the generated spherules and gaps are studied and correlated with the optical transmittance and contact angle measurements at the surface. At optimized exposure time a contact angle of 98° was achieved with 80% optical transmittance. To further increase the hydrophobicity while maintaining optical properties, the hierarchical surfaces were coated with a transparent composite of tetraethyl orthosilicate as precursor and hexamethyldisilazane as silylation agent resulting in an average contact angle of 135.8° and transmittance of around 70%. FTIR and AFM characterization techniques are employed to study the composition and morphology of the generated surfaces.

  4. Structure prediction and binding sites analysis of curcin protein of Jatropha curcas using computational approaches.

    Science.gov (United States)

    Srivastava, Mugdha; Gupta, Shishir K; Abhilash, P C; Singh, Nandita

    2012-07-01

    Ribosome inactivating proteins (RIPs) are defense proteins in a number of higher-plant species that are directly targeted toward herbivores. Jatropha curcas is one of the biodiesel plants having RIPs. The Jatropha seed meal, after extraction of oil, is rich in curcin, a highly toxic RIP similar to ricin, which makes it unsuitable for animal feed. Although the toxicity of curcin is well documented in the literature, the detailed toxic properties and the 3D structure of curcin has not been determined by X-ray crystallography, NMR spectroscopy or any in silico techniques to date. In this pursuit, the structure of curcin was modeled by a composite approach of 3D structure prediction using threading and ab initio modeling. Assessment of model quality was assessed by methods which include Ramachandran plot analysis and Qmean score estimation. Further, we applied the protein-ligand docking approach to identify the r-RNA binding residue of curcin. The present work provides the first structural insight into the binding mode of r-RNA adenine to the curcin protein and forms the basis for designing future inhibitors of curcin. Cloning of a future peptide inhibitor within J. curcas can produce non-toxic varieties of J. curcas, which would make the seed-cake suitable as animal feed without curcin detoxification.

  5. GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

    Science.gov (United States)

    Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

    2016-01-01

    As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation. PMID:27306108

  6. GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

    Science.gov (United States)

    Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

    2016-01-01

    As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.

  7. Agenda Trending: Reciprocity and the Predictive Capacity of Social Networking Sites in Intermedia Agenda Setting across Topics over Time

    Directory of Open Access Journals (Sweden)

    Jacob Groshek

    2013-08-01

    Full Text Available In the contemporary converged media environment, agenda setting is being transformed by the dramatic growth of audiences that are simultaneously media users and producers. The study reported here addresses related gaps in the literature by first comparing the topical agendas of two leading traditional media outlets (New York Times and CNN with the most frequently shared stories and trending topics on two widely popular Social Networking Sites (Facebook and Twitter. Time-series analyses of the most prominent topics identify the extent to which traditional media sets the agenda for social media as well as reciprocal agenda-setting effects of social media topics entering traditional media agendas. In addition, this study examines social intermedia agenda setting topically and across time within social networking sites, and in so doing, adds a vital understanding of where traditional media, online uses, and social media content intersect around instances of focusing events, particularly elections. Findings identify core differences between certain traditional and social media agendas, but also within social media agendas that extend from uses examined here. Additional results further suggest important topical and event-oriented limitations upon the predictive capacit of social networking sites to shape traditional media agendas over time.

  8. Mixed valency and site-preference chemistry for cerium and its compounds: A predictive density-functional theory study

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Aftab [Ames Laboratory; Johnson, Duane D. [Ames Laboratory

    2014-06-01

    Cerium and its technologically relevant compounds are examples of anomalous mixed valency, originating from two competing oxidation states—itinerant Ce4+ and localized Ce3+. Under applied stress, anomalous transitions are observed but not well understood. Here we treat mixed valency as an “alloy” problem involving two valences with competing and numerous site-occupancy configurations. We use density-functional theory with Hubbard U (i.e., DFT+U) to evaluate the effective valence and predict properties, including controlling the valence by pseudoternary alloying. For Ce and its compounds, such as (Ce,La)2(Fe,Co)14B permanent magnets, we find a stable mixed-valent α state near the spectroscopic value of νs=3.53. Ce valency in compounds depends on its steric volume and local chemistry. For La doping, Ce valency shifts towards γ-like Ce3+, as expected from steric volume; for Co doping, valency depends on local Ce-site chemistry and steric volume. Our approach captures the key origins of anomalous valency and site-preference chemistry in complex compounds.

  9. Accurate microRNA target prediction using detailed binding site accessibility and machine learning on proteomics data

    Directory of Open Access Journals (Sweden)

    Martin eReczko

    2012-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small regulatory genes regulating gene expression by targetingmessenger RNA. Though computational methods for miRNA target prediction are the prevailingmeans to analyze their function, they still miss a large fraction of the targeted genes and additionallypredict a large number of false positives. Here we introduce a novel algorithm called DIANAmicroT-ANN which combines multiple novel target site features through an artificial neural network(ANN and is trained using recently published high-throughput data measuring the change of proteinlevels after miRNA overexpression, providing positive and negative targeting examples. The featurescharacterizing each miRNA recognition element include binding structure, conservation level and aspecific profile of structural accessibility. The ANN is trained to integrate the features of eachrecognition element along the 3’ untranslated region into a targeting score, reproducing the relativerepression fold change of the protein. Tested on two different sets the algorithm outperforms otherwidely used algorithms and also predicts a significant number of unique and reliable targets notpredicted by the other methods. For 542 human miRNAs DIANA-microT-ANN predicts 120,000targets not provided by TargetScan 5.0. The algorithm is freely available athttp://microrna.gr/microT-ANN.

  10. Activity after Site-Directed Mutagenesis of CD59 on Complement-Mediated Cytolysis

    Institute of Scientific and Technical Information of China (English)

    Xinhong Zhu; Meihua Gao; Shurong Ren; Qiubo Wang; Cunzhi Lin

    2008-01-01

    CD59 may inhibit the cytolytic activity of complement by binding to C8/C9 and protect host cell membranes against homologous membrane attack complex (MAC). However, CD59 is widely overexpressed on tumor cells,which has been implicated in tumorigenesis. The active site of CD59 relative to MAC is still confused. As reported the MAC binding site is located in the vicinity of a hydrophobic groove on the membrane distal face of the protein centered around residue W40. Here two site-directed mutagenesis were performed by overlapping extension PCR to delete residue W40 site (Mutant 1, M1) or to change C39W40K41 to W39W40W41 (Mutant 2, M2). Then we constructed mutant CD59 eukaryotic expression system and investigated their biological function on CHO cells compared with wild-type CD59. Stable populations of CHO cells expressing recombinant proteins were screened by immunotechnique. After 30 passages culturing, proteins could be tested. Dye release assays suggest that M1CD59 loses the activity against complement, while M2CD59 increases the anti-complement activity slightly.Results indicate that W40 of human CD59 is important to its activity, and prohibition of this site may be a potential way to increase complement activity and to treat tumors.

  11. Modeling Steroid 5alpha-reductase and Characterizing Its Potential Active Sites

    Institute of Scientific and Technical Information of China (English)

    OU Min-Rui; LI Jun-Qian

    2012-01-01

    Steroid 5alpha-reductase of human is an enzyme in the biosynthetic pathway from testosterone (T) to dihydrotestosterone (DHT). Up to now, no crystal structure of this enzyme has been reported. However, knowledge of the tertiary structure and possible active sites is essential for understanding the catalysis mechanism and for the design of inhibitors. A model with putative active sites has been created and evaluated by using homology modeling and molecular docking techniques based on the bioinformatics knowledge. The homology model is optimized in Swiss PDB Viewer with MM method and substrate structures before docking are also optimized on HF/6-31G. The active site for the docking of NADP, T, DHT and Finasteride is located near the N-terminus of enzyme. Four active amino acids in the active site are identified as Ala26, Arg53, Arg176 and Lys177. Reaction procedure, binding pattern of active sites, the types of weak interaction and so on are also discussed.

  12. Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes.

    Science.gov (United States)

    Cockburn, Darrell; Wilkens, Casper; Dilokpimol, Adiphol; Nakai, Hiroyuki; Lewińska, Anna; Abou Hachem, Maher; Svensson, Birte

    2016-01-01

    Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical for the activity of their cognate enzyme, though they are not readily detected in the sequence of a protein, but normally require a crystal structure of a complex for their identification. A variety of methods, including affinity electrophoresis (AE), insoluble polysaccharide pulldown (IPP) and surface plasmon resonance (SPR) have been used to study auxiliary binding sites. These techniques are complementary as AE allows monitoring of binding to soluble polysaccharides, IPP to insoluble polysaccharides and SPR to oligosaccharides. Here we show that these methods are useful not only for analyzing known binding sites, but also for identifying new ones, even without structural data available. We further verify the chosen assays discriminate between known SBS/CBM containing enzymes and negative controls. Altogether 35 enzymes are screened for the presence of SBSs or CBMs and several novel binding sites are identified, including the first SBS ever reported in a cellulase. This work demonstrates that combinations of these methods can be used as a part of routine enzyme characterization to identify new binding sites and advance the study of SBSs and CBMs, allowing them to be detected in the absence of structural data. PMID:27504624

  13. Using Social Cognitive Theory to Predict Physical Activity and Fitness in Underserved Middle School Children

    Science.gov (United States)

    Martin, Jeffrey J.; McCaughtry, Nate; Flory, Sara; Murphy, Anne; Wisdom, Kimberlydawn

    2011-01-01

    Few researchers have used social cognitive theory and environment-based constructs to predict physical activity (PA) and fitness in underserved middle-school children. Hence, we evaluated social cognitive variables and perceptions of the school environment to predict PA and fitness in middle school children (N = 506, ages 10-14 years). Using…

  14. Effects of resource activities upon repository siting and waste containment with reference to bedded salt

    International Nuclear Information System (INIS)

    The primary consideration for the suitability of a nuclear waste repository site is the overall ability of the repository to safely contain radioactive waste. This report is a discussion of the past, present, and future effects of resource activities on waste containment. Past and present resource activities which provide release pathways (i.e., leaky boreholes, adjacent mines) will receive initial evaluation during the early stages of any repository site study. However, other resource activities which may have subtle effects on containment (e.g., long-term pumping causing increased groundwater gradients, invasion of saline water causing lower retardation) and all potential future resource activities must also be considered during the site evaluation process. Resource activities will affect both the siting and the designing of repositories. Ideally, sites should be located in areas of low resource activity and low potential for future activity, and repository design should seek to eliminate or minimize the adverse effects of any resource activity. Buffer zones should be created to provide areas in which resource activities that might adversely affect containment can be restricted or curtailed. This could mean removing large areas of land from resource development. The impact of these frozen assets should be assessed in terms of their economic value and of their effect upon resource reserves. This step could require a major effort in data acquisition and analysis followed by extensive numerical modeling of regional fluid flow and mass transport. Numerical models should be used to assess the effects of resource activity upon containment and should include the cumulative effects of different resource activities. Analysis by other methods is probably not possible except for relatively simple cases

  15. Computational approaches to the determination of active site structures and reaction mechanisms in heterogeneous catalysts.

    Science.gov (United States)

    Catlow, C R A; French, S A; Sokol, A A; Thomas, J M

    2005-04-15

    We apply quantum chemical methods to the study of active site structures and reaction mechanisms in mesoporous silica and metal oxide catalysts. Our approach is based on the use of both molecular cluster and embedded cluster (QM/MM) techniques, where the active site and molecular complex are described using density functional theory (DFT) and the embedding matrix simulated by shell model potentials. We consider three case studies: alkene epoxidation over the microporous TS-1 catalyst; methanol synthesis on ZnO and Cu/ZnO and C-H bond activation over Li-doped MgO. PMID:15901543

  16. Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression.

    Science.gov (United States)

    Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression Exposure to many drugs and environmentally-relevant chemicals can cause adverse outcomes. These adverse outcomes, such as cancer, have been linked to mol...

  17. Sensitivity and predictive uncertainty of the ACASA model at a spruce forest site

    Directory of Open Access Journals (Sweden)

    K. Staudt

    2010-06-01

    Full Text Available The sensitivity and predictive uncertainty of the Advanced Canopy-Atmosphere-Soil Algorithm (ACASA was assessed by employing the Generalized Likelihood Uncertainty Estimation (GLUE method. ACASA is a stand-scale, multi-layer soil-vegetation-atmosphere transfer model that incorporates a third order closure method to simulate the turbulent exchange of energy and matter within and above the canopy. Fluxes simulated by the model were compared to sensible and latent heat fluxes as well as the net ecosystem exchange measured by an eddy-covariance system above the spruce canopy at the FLUXNET-station Waldstein-Weidenbrunnen in the Fichtelgebirge Mountains in Germany. From each of the intensive observation periods carried out within the EGER project (ExchanGE processes in mountainous Regions in autumn 2007 and summer 2008, five days of flux measurements were selected. A large number (20 000 of model runs using randomly generated parameter sets were performed and goodness of fit measures for all fluxes for each of these runs calculated. The 10% best model runs for each flux were used for further investigation of the sensitivity of the fluxes to parameter values and to calculate uncertainty bounds.

    A strong sensitivity of the individual fluxes to a few parameters was observed, such as the leaf area index. However, the sensitivity analysis also revealed the equifinality of many parameters in the ACASA model for the investigated periods. The analysis of two time periods, each representing different meteorological conditions, provided an insight into the seasonal variation of parameter sensitivity. The calculated uncertainty bounds demonstrated that all fluxes were well reproduced by the ACASA model. In general, uncertainty bounds encompass measured values better when these are conditioned on the respective individual flux only and not on all three fluxes concurrently. Structural weaknesses of the ACASA model concerning the soil respiration

  18. Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand

    Energy Technology Data Exchange (ETDEWEB)

    Parashar, Abhinav [Center for Biomedical Research, VIT University, Vellore, Tamil Nadu, 632014 India (India); Venkatachalam, Avanthika [REDOx Lab, PSG Institute of Advanced Studies, Avinashi Road, Peelamedu, Coimbatore, Tamil Nadu, 641004 (India); Gideon, Daniel Andrew [Center for Biomedical Research, VIT University, Vellore, Tamil Nadu, 632014 India (India); Manoj, Kelath Murali, E-mail: satyamjayatu@yahoo.com [REDOx Lab, PSG Institute of Advanced Studies, Avinashi Road, Peelamedu, Coimbatore, Tamil Nadu, 641004 (India)

    2014-12-12

    Highlights: • Cyanide (CN) is a well-studied toxic principle, known to inhibit heme-enzymes. • Inhibition is supposed to result from CN binding at the active site as a ligand. • Diverse heme enzymes’ CN inhibition profiles challenge prevailing mechanism. • Poor binding efficiency of CN at low enzyme concentrations and ligand pressures. • CN-based diffusible radicals cause ‘non-productive electron transfers’ (inhibition). - Abstract: The toxicity of cyanide is hitherto attributed to its ability to bind to heme proteins’ active site and thereby inhibit their activity. It is shown herein that the long-held interpretation is inadequate to explain several observations in heme-enzyme reaction systems. Generation of cyanide-based diffusible radicals in heme-enzyme reaction milieu could shunt electron transfers (by non-active site processes), and thus be detrimental to the efficiency of oxidative outcomes.

  19. Structure-based activity prediction for an enzyme of unknown function

    OpenAIRE

    Hermann, Johannes C.; Marti-Arbona, Ricardo; Fedorov, Alexander A.; Fedorov, Elena; Almo, Steven C.; Shoichet, Brian K.; Raushel, Frank M.

    2007-01-01

    With many genomes sequenced, a pressing challenge in biology is predicting the function of the proteins that the genes encode. When proteins are unrelated to others of known activity, bioinformatics inference for function becomes problematic. It would thus be useful to interrogate protein structures for function directly. Here, we predict the function of an enzyme of unknown activity, Tm0936 from Thermotoga maritima, by docking high-energy intermediate forms of thousands of candidate metaboli...

  20. Crystal structure of an avian influenza polymerase PA[subscript N] reveals an endonuclease active site

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Puwei; Bartlam, Mark; Lou, Zhiyong; Chen, Shoudeng; Zhou, Jie; He, Xiaojing; Lv, Zongyang; Ge, Ruowen; Li, Xuemei; Deng, Tao; Fodor, Ervin; Rao, Zihe; Liu, Yingfang; (NU Sinapore); (Nankai); (Oxford); (Chinese Aca. Sci.); (Tsinghua)

    2009-11-10

    The heterotrimeric influenza virus polymerase, containing the PA, PB1 and PB2 proteins, catalyses viral RNA replication and transcription in the nucleus of infected cells. PB1 holds the polymerase active site and reportedly harbours endonuclease activity, whereas PB2 is responsible for cap binding. The PA amino terminus is understood to be the major functional part of the PA protein and has been implicated in several roles, including endonuclease and protease activities as well as viral RNA/complementary RNA promoter binding. Here we report the 2.2 angstrom (A) crystal structure of the N-terminal 197 residues of PA, termed PA(N), from an avian influenza H5N1 virus. The PA(N) structure has an alpha/beta architecture and reveals a bound magnesium ion coordinated by a motif similar to the (P)DX(N)(D/E)XK motif characteristic of many endonucleases. Structural comparisons and mutagenesis analysis of the motif identified in PA(N) provide further evidence that PA(N) holds an endonuclease active site. Furthermore, functional analysis with in vivo ribonucleoprotein reconstitution and direct in vitro endonuclease assays strongly suggest that PA(N) holds the endonuclease active site and has critical roles in endonuclease activity of the influenza virus polymerase, rather than PB1. The high conservation of this endonuclease active site among influenza strains indicates that PA(N) is an important target for the design of new anti-influenza therapeutics.

  1. Prediction of the key binding site of odorant-binding protein of Holotrichia oblita Faldermann (Coleoptera: Scarabaeida).

    Science.gov (United States)

    Zhuang, X; Wang, Q; Wang, B; Zhong, T; Cao, Y; Li, K; Yin, J

    2014-06-01

    The scarab beetle Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae) is a predominant underground pest in the northern parts of China, and its larvae (grubs) cause great economic losses because of its wide range of host plants and covert habitats. Environmentally friendly strategies for controlling adults would have novel and broad potential applications. One potential pest management measure is the regulation of olfactory chemoreception to control target insect pests. In the process of olfactory recognition, odorant-binding proteins (OBPs) are believed to carry hydrophobic odorants from the environment to the surface of olfactory receptor neurons. To obtain a better understanding of the relationship between OBP structures and their ligands, homology modelling and molecular docking have been conducted on the interaction between HoblOBP1 and hexyl benzoate in the present study. Based on the results, site-directed mutagenesis and binding experiments were combined to describe the binding sites of HoblOBP1 and to explore its ligand-binding mechanism. After homology modelling of HoblOBP1, it was found that the three-dimensional structure of HoblOBP1 consists of six α-helices and three disulphide bridges that connect the helices, and the hydrophobic pockets are both composed of five helices. Based on the docking study, we found that van der Waals interactions and hydrophobic interactions are both important in the bonding between HoblOBP1 and hexyl benzoate. Intramolecular residues formed the hydrogen bonds in the C terminus of the protein and the bonds are crucial for the ligand-binding specificity. Finally, MET48, ILE80 and TYR111 are binding sites predicted for HoblOBP1. Using site-directed mutagenesis and fluorescence assays, it was found that ligands could not be recognized by mutant of Tyr111. A possible explanation is that the compound could not be recognized by the mutant, and remains in the binding cavity because of the loss of the intramolecular

  2. Large zinc cation occupancy of octahedral sites in mechanically activated zinc ferrite powders

    International Nuclear Information System (INIS)

    The cation site occupancy of a mechanically activated nanocrystalline zinc ferrite powder was determined as (Zn0.552+Fe0.183+)tet[Zr0.452+Fe1.823+]octO4 through analysis of extended x-ray absorption fine structure measurements, showing a large redistribution of cations between sites compared to normal zinc ferrite samples. The overpopulation of cations in the octahedral sites was attributed to the ascendance in importance of the ionic radii over the crystal energy and bonding coordination in determining which interstitial sites are occupied in this structurally disordered powder. Slight changes are observed in the local atomic environment about the zinc cations, but not the iron cations, with respect to the spinel structure. The presence of Fe3+ on both sites is consistent with the measured room temperature magnetic properties. (c) 2000 American Institute of Physics

  3. Prediction

    CERN Document Server

    Sornette, Didier

    2010-01-01

    This chapter first presents a rather personal view of some different aspects of predictability, going in crescendo from simple linear systems to high-dimensional nonlinear systems with stochastic forcing, which exhibit emergent properties such as phase transitions and regime shifts. Then, a detailed correspondence between the phenomenology of earthquakes, financial crashes and epileptic seizures is offered. The presented statistical evidence provides the substance of a general phase diagram for understanding the many facets of the spatio-temporal organization of these systems. A key insight is to organize the evidence and mechanisms in terms of two summarizing measures: (i) amplitude of disorder or heterogeneity in the system and (ii) level of coupling or interaction strength among the system's components. On the basis of the recently identified remarkable correspondence between earthquakes and seizures, we present detailed information on a class of stochastic point processes that has been found to be particu...

  4. The toponymy of communal activity: Anglo-Saxon assembly sites and their functions

    OpenAIRE

    Baker, John

    2014-01-01

    The paper builds on earlier discussion of the multiple functions of medieval judicial assembly sites, providing a comprehensive evaluation of relevant English hundred-names, and making reference to associated microtoponymy. While religious, military, commercial, and recreational activities may all have occurred at assembly-sites, it can be hard to delineate the evidence so clearly along these lines, and attempts to do so may be anachronistic in some instances; nevertheless, the analysis of di...

  5. Identification of essential histidine residues in the active site of Escherichia coli xylose (glucose) isomerase.

    OpenAIRE

    Batt, C A; Jamieson, A. C.; Vandeyar, M A

    1990-01-01

    Two conserved histidine residues (His-101 and His-271) appear to be essential components in the active site of the enzyme xylose (glucose) isomerase (EC 5.3.1.5). These amino acid residues were targeted for mutagenesis on the basis of sequence homology among xylose isomerases isolated from Escherichia coli, Bacillus subtilis, Ampullariella sp. strain 3876, and Streptomyces violaceus-niger. Each residue was selectively replaced by site-directed mutagenesis and shown to be essential for activit...

  6. Residents’ Environmental Conservation Behaviors at Tourist Sites: Broadening the Norm Activation Framework by Adopting Environment Attachment

    OpenAIRE

    Yuling Zhang; Jie Zhang; Yuyao Ye; Qitao Wu; Lixia Jin; Hongou Zhang

    2016-01-01

    Understanding the factors that affect residents’ environmental conservation behaviors help in managing the environment of tourist sites. This research provides an integrative understanding of how residents near tourist sites form their environmental conservation behaviors by merging the norm-activation model and cognitive-affective model into one theoretical framework. Results of the structural analysis from a sample of 642 residents showed that this study’s proposed composite model includes ...

  7. Modified Active Site Coordination in a Clinical Mutant of Sulfite Oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Doonan, C.J.; Wilson, H.L.; Rajagopalan, K.V.; Garrett, R.M.; Bennett, B.; Prince, R.C.; George, G.N.

    2009-06-02

    The molybdenum site of the Arginine 160 {yields} Glutamine clinical mutant of the physiologically vital enzyme sulfite oxidase has been investigated by a combination of X-ray absorption spectroscopy and density functional theory calculations. We conclude that the mutant enzyme has a six-coordinate pseudo-octahedral active site with coordination of Glutamine O{sup {epsilon}} to molybdenum. This contrasts with the wild-type enzyme which is five-coordinate with approximately square-based pyramidal geometry. This difference in the structure of the molybdenum site explains many of the properties of the mutant enzyme which have previously been reported.

  8. Comparative study to predict dipeptidyl peptidase IV inhibitory activity of β-amino amide scaffold

    Directory of Open Access Journals (Sweden)

    S Patil

    2015-01-01

    Full Text Available Comparative study was performed on 34 β-amino amide derivatives as dipeptidyl peptidase IV inhibitors in order to determine their structural requirement to enhance the antidiabetic activities. Hologram quantitative structure activity relationships models utilized specialized fragment fingerprints (hologram length 353 which showed good predictivity with cross-validated q 2 and conventional r 2 values of 0.971 and 0.971, respectively. Models were validated and optimized by a test set of eight compounds and gave satisfactory predictive ability. Hologram quantitative structure activity relationships maps were helpful in prediction of the structural features of the ligands to account for the activity in terms of positively and negatively contributing towards activity. The information obtained from maps could be effectively use as a guiding tool for further structure modifications and synthesis of new potent antidiabetic agents.

  9. Predicting involvement in prison gang activity: street gang membership, social and psychological factors.

    Science.gov (United States)

    Wood, Jane L; Alleyne, Emma; Mozova, Katarina; James, Mark

    2014-06-01

    The aim of this study was to examine whether street gang membership, psychological factors, and social factors such as preprison experiences could predict young offenders' involvement in prison gang activity. Data were collected via individual interviews with 188 young offenders held in a Young Offenders Institution in the United Kingdom. Results showed that psychological factors such as the value individuals attached to social status, a social dominance orientation, and antiauthority attitudes were important in predicting young offenders' involvement in prison gang activity. Further important predictors included preimprisonment events such as levels of threat, levels of individual delinquency, and levels of involvement in group crime. Longer current sentences also predicted involvement in prison gang activity. However, street gang membership was not an important predictor of involvement in prison gang activity. These findings have implications for identifying prisoners involved in prison gang activity and for considering the role of psychological factors and group processes in gang research.

  10. Conformational Change in the Active Site of Streptococcal Unsaturated Glucuronyl Hydrolase Through Site-Directed Mutagenesis at Asp-115.

    Science.gov (United States)

    Nakamichi, Yusuke; Oiki, Sayoko; Mikami, Bunzo; Murata, Kousaku; Hashimoto, Wataru

    2016-08-01

    Bacterial unsaturated glucuronyl hydrolase (UGL) degrades unsaturated disaccharides generated from mammalian extracellular matrices, glycosaminoglycans, by polysaccharide lyases. Two Asp residues, Asp-115 and Asp-175 of Streptococcus agalactiae UGL (SagUGL), are completely conserved in other bacterial UGLs, one of which (Asp-175 of SagUGL) acts as a general acid and base catalyst. The other Asp (Asp-115 of SagUGL) also affects the enzyme activity, although its role in the enzyme reaction has not been well understood. Here, we show substitution of Asp-115 in SagUGL with Asn caused a conformational change in the active site. Tertiary structures of SagUGL mutants D115N and D115N/K370S with negligible enzyme activity were determined at 2.00 and 1.79 Å resolution, respectively, by X-ray crystallography. The side chain of Asn-115 is drastically shifted in both mutants owing to the interaction with several residues, including Asp-175, by formation of hydrogen bonds. This interaction between Asn-115 and Asp-175 probably prevents the mutants from triggering the enzyme reaction using Asp-175 as an acid catalyst. PMID:27402448

  11. New Quantitative Structure-Activity Relationship Models Improve Predictability of Ames Mutagenicity for Aromatic Azo Compounds.

    Science.gov (United States)

    Manganelli, Serena; Benfenati, Emilio; Manganaro, Alberto; Kulkarni, Sunil; Barton-Maclaren, Tara S; Honma, Masamitsu

    2016-10-01

    Existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for aromatic azo compounds. In this study, 2 new models were built to predict Ames mutagenicity of this class of compounds. The first one made use of descriptors based on simplified molecular input-line entry system (SMILES), calculated with the CORAL software. The second model was based on the k-nearest neighbors algorithm. The statistical quality of the predictions from single models was satisfactory. The performance further improved when the predictions from these models were combined. The prediction results from other QSAR models for mutagenicity were also evaluated. Most of the existing models were found to be good at finding toxic compounds but resulted in many false positive predictions. The 2 new models specific for this class of compounds avoid this problem thanks to a larger set of related compounds as training set and improved algorithms.

  12. Radionuclide migration in ground water at a low-level waste disposal site: a comparison of predicted radionuclide transport modeling versus field observations

    International Nuclear Information System (INIS)

    At the Chalk River Nuclear Laboratories (CRNL), in Ontario, Canada, a number of LLW shallow-land burial facilities have existed for 25-30 years. These facilities are useful for testing the concept of site modelability. In 1984, CRNL and the Pacific Northwest Laboratory (PNL) established a cooperative research program to examine two disposal sites having plumes of slightly contaminated ground water for study. This report addresses the LLW Nitrate Disposal Pit site, which received liquid wastes containing approximately 1000-1500 curies of mixed fission products during 1953-54. The objective of this study is to test the regulatory requirement that a site be modeled and to use the Nitrate Disposal Pit site as a field site for testing the reliability of models in predicting radionuclide movement in ground water. The study plan was to approach this site as though it were to be licensed under the requirements of 10 CFR 61. Under the assumption that little was known about this site, a characterization plan was prepared describing the geologic, hydrologic, and geochemical information needed to assess site performance. After completion of the plan, site data generated by CRNL were selected to fill the plan data requirements. This paper describes the site hydrogeology, modeling of ground water flow, the comparison of observed and predicted radionuclide movement, and summarizes the conclusions and recommendations. 3 references, 10 figures

  13. Predicting Social Networking Site Use and Online Communication Practices among Adolescents: The Role of Access and Device Ownership

    Directory of Open Access Journals (Sweden)

    Drew P. Cingel

    2014-06-01

    Full Text Available Given adolescents' heavy social media use, this study examined a number of predictors of adolescent social media use, as well as predictors of online communication practices. Using data collected from a national sample of 467 adolescents between the ages of 13 and 17, results indicate that demographics, technology access, and technology ownership are related to social media use and communication practices. Specifically, females log onto and use more constructive com-munication practices on Facebook compared to males. Additionally, adolescents who own smartphones engage in more constructive online communication practices than those who share regular cell phones or those who do not have access to a cell phone. Overall, results imply that ownership of mobile technologies, such as smartphones and iPads, may be more predictive of social networking site use and online communication practices than general ownership of technology.

  14. Predicting Social Networking Site Use and Online Communication Practices among Adolescents: The Role of Access and Device Ownership

    Directory of Open Access Journals (Sweden)

    Drew P. Cingel

    2014-01-01

    Full Text Available Given adolescents' heavy social media use, this study examined a number of predictors of adolescent social media use, as well as predictors of online communication practices. Using data collected from a national sample of 467 adolescents between the ages of 13 and 17, results indicate that demographics, technology access, and technology ownership are related to social media use and communication practices. Specifically, females log onto and use more constructive communication practices on Facebook compared to males. Additionally, adolescents who own smartphones engage in more constructive online communication practices than those who share regular cell phones or those who do not have access to a cell phone. Overall, results imply that ownership of mobile technologies, such as smartphones and iPads, may be more predictive of social networking site use and online communication practices than general ownership of technology.

  15. The use of early summer mosquito surveillance to predict late summer West Nile virus activity

    Science.gov (United States)

    Ginsberg, Howard S.; Rochlin, Ilia; Campbell, Scott R.

    2010-01-01

    Utility of early-season mosquito surveillance to predict West Nile virus activity in late summer was assessed in Suffolk County, NY. Dry ice-baited CDC miniature light traps paired with gravid traps were set weekly. Maximum-likelihood estimates of WNV positivity, minimum infection rates, and % positive pools were generally well correlated. However, positivity in gravid traps was not correlated with positivity in CDC light traps. The best early-season predictors of WNV activity in late summer (estimated using maximum-likelihood estimates of Culex positivity in August and September) were early date of first positive pool, low numbers of mosquitoes in July, and low numbers of mosquito species in July. These results suggest that early-season entomological samples can be used to predict WNV activity later in the summer, when most human cases are acquired. Additional research is needed to establish which surveillance variables are most predictive and to characterize the reliability of the predictions.

  16. Improving the neutral phytase activity from Bacillus amyloliquefaciens DSM 1061 by site-directed mutagenesis.

    Science.gov (United States)

    Xu, Wei; Shao, Rong; Wang, Zupeng; Yan, Xiuhua

    2015-03-01

    Neutral phytase is used as a feed additive for degradation of anti-nutritional phytate in aquatic feed industry. Site-directed mutagenesis of Bacillus amyloliquefaciens DSM 1061 phytase was performed with an aim to increase its activity. Mutation residues were chosen based on multiple sequence alignments and structure analysis of neutral phytsaes from different microorganisms. The mutation sites on surface (D148E, S197E and N156E) and around the active site (D52E) of phytase were selected. Analysis of the phytase variants showed that the specific activities of mutants D148E and S197E remarkably increased by about 35 and 13% over a temperature range of 40-75 °C at pH 7.0, respectively. The k cat of mutants D148E and S197E were 1.50 and 1.25 times than that of the wild-type phytase, respectively. Both D148E and S197E showed much higher thermostability than that of the wild-type phytase. However, mutants N156E and D52E led to significant loss of specific activity of the enzyme. Structural analysis revealed that these mutations may affect conformation of the active site of phytase. The present mutant phytases D148E and S197E with increased activities and thermostabilities have application potential as additives in aquaculture feed. PMID:25613522

  17. Stringency of the 2-His-1-Asp active-site motif in prolyl 4-hydroxylase.

    Directory of Open Access Journals (Sweden)

    Kelly L Gorres

    Full Text Available The non-heme iron(II dioxygenase family of enzymes contain a common 2-His-1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C-H bonds. Prolyl 4-hydroxylase (P4H is an alpha-ketoglutarate-dependent iron(II dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His-1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change.

  18. Quantum delocalization of protons in the hydrogen bond network of an enzyme active site

    CERN Document Server

    Wang, Lu; Boxer, Steven G; Markland, Thomas E

    2015-01-01

    Enzymes utilize protein architectures to create highly specialized structural motifs that can greatly enhance the rates of complex chemical transformations. Here we use experiments, combined with ab initio simulations that exactly include nuclear quantum effects, to show that a triad of strongly hydrogen bonded tyrosine residues within the active site of the enzyme ketosteroid isomerase (KSI) facilitates quantum proton delocalization. This delocalization dramatically stabilizes the deprotonation of an active site tyrosine residue, resulting in a very large isotope effect on its acidity. When an intermediate analog is docked, it is incorporated into the hydrogen bond network, giving rise to extended quantum proton delocalization in the active site. These results shed light on the role of nuclear quantum effects in the hydrogen bond network that stabilizes the reactive intermediate of KSI, and the behavior of protons in biological systems containing strong hydrogen bonds.

  19. Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation

    DEFF Research Database (Denmark)

    Elling, Christian E; Frimurer, Thomas M; Gerlach, Lars-Ole;

    2006-01-01

    for monoamine binding in TM-III, was used as the starting point to engineer activating metal ion sites between the extracellular segments of the beta2-adrenergic receptor. Cu(II) and Zn(II) alone and in complex with aromatic chelators acted as potent (EC50 decreased to 0.5 microm) and efficacious agonists...... in sites constructed between positions III:08 (Asp or His), VI:16 (preferentially Cys), and/or VII:06 (preferentially Cys). In molecular models built over the backbone conformation of the inactive rhodopsin structure, the heavy atoms that coordinate the metal ion were located too far away from each other...... to form high affinity metal ion sites in both the bidentate and potential tridentate settings. This indicates that the residues involved in the main ligand-binding pocket will have to move closer to each other during receptor activation. On the basis of the distance constraints from these activating metal...

  20. Improvement of AEP Predictions Using Diurnal CFD Modelling with Site-Specific Stability Weightings Provided from Mesoscale Simulation

    Science.gov (United States)

    Hristov, Y.; Oxley, G.; Žagar, M.

    2014-06-01

    The Bolund measurement campaign, performed by Danish Technical University (DTU) Wind Energy Department (also known as RISØ), provided significant insight into wind flow modeling over complex terrain. In the blind comparison study several modelling solutions were submitted with the vast majority being steady-state Computational Fluid Dynamics (CFD) approaches with two equation k-epsilon turbulence closure. This approach yielded the most accurate results, and was identified as the state-of-the-art tool for wind turbine generator (WTG) micro-siting. Based on the findings from Bolund, further comparison between CFD and field measurement data has been deemed essential in order to improve simulation accuracy for turbine load and long-term Annual Energy Production (AEP) estimations. Vestas Wind Systems A/S is a major WTG original equipment manufacturer (OEM) with an installed base of over 60GW in over 70 countries accounting for 19% of the global installed base. The Vestas Performance and Diagnostic Centre (VPDC) provides online live data to more than 47GW of these turbines allowing a comprehensive comparison between modelled and real-world energy production data. In previous studies, multiple sites have been simulated with a steady neutral CFD formulation for the atmospheric surface layer (ASL), and wind resource (RSF) files have been generated as a base for long-term AEP predictions showing significant improvement over predictions performed with the industry standard linear WAsP tool. In this study, further improvements to the wind resource file generation with CFD are examined using an unsteady diurnal cycle approach with a full atmospheric boundary layer (ABL) formulation, with the unique stratifications throughout the cycle weighted according to mesoscale simulated sectorwise stability frequencies.

  1. Improvement of AEP Predictions Using Diurnal CFD Modelling with Site-Specific Stability Weightings Provided from Mesoscale Simulation

    International Nuclear Information System (INIS)

    The Bolund measurement campaign, performed by Danish Technical University (DTU) Wind Energy Department (also known as RISØ), provided significant insight into wind flow modeling over complex terrain. In the blind comparison study several modelling solutions were submitted with the vast majority being steady-state Computational Fluid Dynamics (CFD) approaches with two equation k-ε turbulence closure. This approach yielded the most accurate results, and was identified as the state-of-the-art tool for wind turbine generator (WTG) micro-siting. Based on the findings from Bolund, further comparison between CFD and field measurement data has been deemed essential in order to improve simulation accuracy for turbine load and long-term Annual Energy Production (AEP) estimations. Vestas Wind Systems A/S is a major WTG original equipment manufacturer (OEM) with an installed base of over 60GW in over 70 countries accounting for 19% of the global installed base. The Vestas Performance and Diagnostic Centre (VPDC) provides online live data to more than 47GW of these turbines allowing a comprehensive comparison between modelled and real-world energy production data. In previous studies, multiple sites have been simulated with a steady neutral CFD formulation for the atmospheric surface layer (ASL), and wind resource (RSF) files have been generated as a base for long-term AEP predictions showing significant improvement over predictions performed with the industry standard linear WAsP tool. In this study, further improvements to the wind resource file generation with CFD are examined using an unsteady diurnal cycle approach with a full atmospheric boundary layer (ABL) formulation, with the unique stratifications throughout the cycle weighted according to mesoscale simulated sectorwise stability frequencies

  2. Mutations Closer to the Active Site Improve the Promiscuous Aldolase Activity of 4-Oxalocrotonate Tautomerase More Effectively than Distant Mutations.

    Science.gov (United States)

    Rahimi, Mehran; van der Meer, Jan-Ytzen; Geertsema, Edzard M; Poddar, Harshwardhan; Baas, Bert-Jan; Poelarends, Gerrit J

    2016-07-01

    The enzyme 4-oxalocrotonate tautomerase (4-OT), which catalyzes enol-keto tautomerization as part of a degradative pathway for aromatic hydrocarbons, promiscuously catalyzes various carbon-carbon bond-forming reactions. These include the aldol condensation of acetaldehyde with benzaldehyde to yield cinnamaldehyde. Here, we demonstrate that 4-OT can be engineered into a more efficient aldolase for this condensation reaction, with a >5000-fold improvement in catalytic efficiency (kcat /Km ) and a >10(7) -fold change in reaction specificity, by exploring small libraries in which only "hotspots" are varied. The hotspots were identified by systematic mutagenesis (covering each residue), followed by a screen for single mutations that give a strong improvement in the desired aldolase activity. All beneficial mutations were near the active site of 4-OT, thus underpinning the notion that new catalytic activities of a promiscuous enzyme are more effectively enhanced by mutations close to the active site. PMID:27238293

  3. Testing the applicability of rapid on-site enzymatic activity detection for surface water monitoring

    Science.gov (United States)

    Stadler, Philipp; Vogl, Wolfgang; Juri, Koschelnik; Markus, Epp; Maximilian, Lackner; Markus, Oismüller; Monika, Kumpan; Peter, Strauss; Regina, Sommer; Gabriela, Ryzinska-Paier; Farnleitner Andreas, H.; Matthias, Zessner

    2015-04-01

    On-site detection of enzymatic activities has been suggested as a rapid surrogate for microbiological pollution monitoring of water resources (e.g. using glucuronidases, galactosidases, esterases). Due to the possible short measuring intervals enzymatic methods have high potential as near-real time water quality monitoring tools. This presentation describes results from a long termed field test. For twelve months, two ColiMinder devices (Vienna Water Monitoring, Austria) for on-site determination of enzymatic activity were tested for stream water monitoring at the experimental catchment HOAL (Hydrological Open Air Laboratory, Center for Water Resource Systems, Vienna University of Technology). The devices were overall able to follow and reflect the diverse hydrological and microbiological conditions of the monitored stream during the test period. Continuous data in high temporal resolution captured the course of enzymatic activity in stream water during diverse rainfall events. The method also proofed sensitive enough to determine diurnal fluctuations of enzymatic activity in stream water during dry periods. The method was able to capture a seasonal trend of enzymatic activity in stream water that matches the results gained from Colilert18 analysis for E. coli and coliform bacteria of monthly grab samples. Furthermore the comparison of ColiMinder data with measurements gained at the same test site with devices using the same method but having different construction design (BACTcontrol, microLAN) showed consistent measuring results. Comparative analysis showed significant differences between measured enzymatic activity (modified fishman units and pmol/min/100ml) and cultivation based analyses (most probable number, colony forming unit). Methods of enzymatic activity measures are capable to detect ideally the enzymatic activity caused by all active target bacteria members, including VBNC (viable but nonculturable) while cultivation based methods cannot detect VBNC

  4. Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site

    Directory of Open Access Journals (Sweden)

    Soares Alexei S

    2007-11-01

    Full Text Available Abstract Background Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions. Results We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a ΔH of -13 ± 2 kJ/mol and a ΔS of -0.04 ± 0.01 kJ/(K*mol. The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site. Conclusion We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the

  5. Threatened and endangered wildlife species of the Hanford Site related to CERCLA characterization activities

    Energy Technology Data Exchange (ETDEWEB)

    Fitzner, R.E. [Pacific Northwest Lab., Richland, WA (United States); Weiss, S.G.; Stegen, J.A. [Westinghouse Hanford Co., Richland, WA (United States)

    1994-06-01

    The US Department of Energy`s (DOE) Hanford Site has been placed on the National Priorities List, which requires that it be remediated under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) or Superfund. Potentially contaminated areas of the Hanford Site were grouped into operable units, and detailed characterization and investigation plans were formulated. The DOE Richland Operations Office requested Westinghouse Hanford Company (WHC) to conduct a biological assessment of the potential impact of these characterization activities on the threatened, endangered, and sensitive wildlife species of the Hanford Site. Additional direction for WHC compliances with wildlife protection can be found in the Environmental Compliance Manual. This document is intended to meet these requirements, in part, for the CERCLA characterization activities, as well as for other work comparable in scope. This report documents the biological assessment and describes the pertinent components of the Hanford Site as well as the planned characterization activities. Also provided are accounts of endangered, threatened, and federal candidate wildlife species on the Hanford Site and information as to how human disturbances can affect these species. Potential effects of the characterization activities are described with recommendations for mitigation measures.

  6. The active site of low-temperature methane hydroxylation in iron-containing zeolites

    Science.gov (United States)

    Snyder, Benjamin E. R.; Vanelderen, Pieter; Bols, Max L.; Hallaert, Simon D.; Böttger, Lars H.; Ungur, Liviu; Pierloot, Kristine; Schoonheydt, Robert A.; Sels, Bert F.; Solomon, Edward I.

    2016-08-01

    An efficient catalytic process for converting methane into methanol could have far-reaching economic implications. Iron-containing zeolites (microporous aluminosilicate minerals) are noteworthy in this regard, having an outstanding ability to hydroxylate methane rapidly at room temperature to form methanol. Reactivity occurs at an extra-lattice active site called α-Fe(II), which is activated by nitrous oxide to form the reactive intermediate α-O; however, despite nearly three decades of research, the nature of the active site and the factors determining its exceptional reactivity are unclear. The main difficulty is that the reactive species—α-Fe(II) and α-O—are challenging to probe spectroscopically: data from bulk techniques such as X-ray absorption spectroscopy and magnetic susceptibility are complicated by contributions from inactive ‘spectator’ iron. Here we show that a site-selective spectroscopic method regularly used in bioinorganic chemistry can overcome this problem. Magnetic circular dichroism reveals α-Fe(II) to be a mononuclear, high-spin, square planar Fe(II) site, while the reactive intermediate, α-O, is a mononuclear, high-spin Fe(IV)=O species, whose exceptional reactivity derives from a constrained coordination geometry enforced by the zeolite lattice. These findings illustrate the value of our approach to exploring active sites in heterogeneous systems. The results also suggest that using matrix constraints to activate metal sites for function—producing what is known in the context of metalloenzymes as an ‘entatic’ state—might be a useful way to tune the activity of heterogeneous catalysts.

  7. The active site of low-temperature methane hydroxylation in iron-containing zeolites.

    Science.gov (United States)

    Snyder, Benjamin E R; Vanelderen, Pieter; Bols, Max L; Hallaert, Simon D; Böttger, Lars H; Ungur, Liviu; Pierloot, Kristine; Schoonheydt, Robert A; Sels, Bert F; Solomon, Edward I

    2016-08-18

    An efficient catalytic process for converting methane into methanol could have far-reaching economic implications. Iron-containing zeolites (microporous aluminosilicate minerals) are noteworthy in this regard, having an outstanding ability to hydroxylate methane rapidly at room temperature to form methanol. Reactivity occurs at an extra-lattice active site called α-Fe(ii), which is activated by nitrous oxide to form the reactive intermediate α-O; however, despite nearly three decades of research, the nature of the active site and the factors determining its exceptional reactivity are unclear. The main difficulty is that the reactive species-α-Fe(ii) and α-O-are challenging to probe spectroscopically: data from bulk techniques such as X-ray absorption spectroscopy and magnetic susceptibility are complicated by contributions from inactive 'spectator' iron. Here we show that a site-selective spectroscopic method regularly used in bioinorganic chemistry can overcome this problem. Magnetic circular dichroism reveals α-Fe(ii) to be a mononuclear, high-spin, square planar Fe(ii) site, while the reactive intermediate, α-O, is a mononuclear, high-spin Fe(iv)=O species, whose exceptional reactivity derives from a constrained coordination geometry enforced by the zeolite lattice. These findings illustrate the value of our approach to exploring active sites in heterogeneous systems. The results also suggest that using matrix constraints to activate metal sites for function-producing what is known in the context of metalloenzymes as an 'entatic' state-might be a useful way to tune the activity of heterogeneous catalysts. PMID:27535535

  8. Preliminary examination of the impacts of repository site characterization activities and facility construction and operation activities on Hanford air quality

    Energy Technology Data Exchange (ETDEWEB)

    Glantz, C.S.; Ramsdell, J.V.

    1986-04-01

    Air quality impacts that would result from site characterization activities and from the construction and operation of a high-level nuclear wste repository at Hanford are estimated using two simple atmospheric dispersion models, HANCHI and CHISHORT. Model results indicate that pollutant concentrations would not exceed ambient air quality standards at any point outside the Hanford fenceline or at any publicly accessible location within the Hanford Site. The increase in pollutant concentrations in nearby communities due to site activities would be minimal. HANCHI and CHISHORT are documented in the appendices of this document. Further study of the repository's impact on air quality will be conducted when more detailed project plans and work schedules are available.

  9. Conserved phosphorylation sites in the activation loop of the Arabidopsis phytosulfokine receptor PSKR1 differentially affect kinase and receptor activity.

    Science.gov (United States)

    Hartmann, Jens; Linke, Dennis; Bönniger, Christine; Tholey, Andreas; Sauter, Margret

    2015-12-15

    PSK (phytosulfokine) is a plant peptide hormone perceived by a leucine-rich repeat receptor kinase. Phosphosite mapping of epitope-tagged PSKR1 (phytosulfokine receptor 1) from Arabidopsis thaliana plants identified Ser(696) and Ser(698) in the JM (juxtamembrane) region and probably Ser(886) and/or Ser(893) in the AL (activation loop) as in planta phosphorylation sites. In vitro-expressed kinase was autophosphorylated at Ser(717) in the JM, and at Ser(733), Thr(752), Ser(783), Ser(864), Ser(911), Ser(958) and Thr(998) in the kinase domain. The LC-ESI-MS/MS spectra provided support that up to three sites (Thr(890), Ser(893) and Thr(894)) in the AL were likely to be phosphorylated in vitro. These sites are evolutionarily highly conserved in PSK receptors, indicative of a conserved function. Site-directed mutagenesis of the four conserved residues in the activation segment, Thr(890), Ser(893), Thr(894) and Thr(899), differentially altered kinase activity in vitro and growth-promoting activity in planta. The T899A and the quadruple-mutated TSTT-A (T890A/S893A/T894A/T899A) mutants were both kinase-inactive, but PSKR1(T899A) retained growth-promoting activity. The T890A and S893A/T894A substitutions diminished kinase activity and growth promotion. We hypothesize that phosphorylation within the AL activates kinase activity and receptor function in a gradual and distinctive manner that may be a means to modulate the PSK response. PMID:26472115

  10. Utility experiences in redevelopment of formerly used sites -- Wisconsin Electric's risk management and economic development activities

    International Nuclear Information System (INIS)

    Wisconsin Electric Power Company, which recently celebrated its 100th anniversary, has actively promoted the redevelopment of its former sites as well as those of its customers. Serving Milwaukee and southeast Wisconsin, Wisconsin Electric's (WE) sites include former power plants, landfills, right-of-ways, and manufactured gas plant sites. In setting an example for others, as well as seeking to maximize the economic value of these sites, WE has either redeveloped or promoted the redevelopment of these sites by others. Examples include the East Wells Power Plant (now home of the Milwaukee Repertory Theater), the Lakeside Power Plant Site (now the home of Harnischfeger Corporation's headquarters), and the Commerce Street Power Plant located on the Milwaukee River near downtown Milwaukee. In each case the company evaluated the potential environmental liabilities against the unrealized asset value derived from facility location, site size, architectural uniqueness, or other characteristics. At the Commerce Street Power Plant, walking distance to the downtown Milwaukee business district combined with river frontage, were significant site values leveraged against a $5 million asbestos and lead-based paint removal project done to prepare the plant for marketing. More recently, WE has used its experience in promoting the redevelopment of the Menomonee River Valley, the original core of Milwaukee's industrial community, and in advancing a more practical regulatory approach to redeveloping older sites. Finally, the company is working with a non-profit community health clinic, community groups and local foundations in linking these redevelopment activities with the economic and physical health of inner city residents

  11. New active drugs against liver stages of Plasmodium predicted by molecular topology.

    NARCIS (Netherlands)

    Mahmoudi, N.; Garcia-Domenech, R.; Galvez, J.; Farhati, K.; Franetich, J.F.; Sauerwein, R.W.; Hannoun, L.; Derouin, F.; Danis, M.; Mazier, D.

    2008-01-01

    We conducted a quantitative structure-activity relationship (QSAR) study based on a database of 127 compounds previously tested against the liver stage of Plasmodium yoelii in order to develop a model capable of predicting the in vitro antimalarial activities of new compounds. Topological indices we

  12. Prediction of in vitro and in vivo oestrogen receptor activity using hierarchical clustering

    Science.gov (United States)

    In this study, hierarchical clustering classification models were developed to predict in vitro and in vivo oestrogen receptor (ER) activity. Classification models were developed for binding, agonist, and antagonist in vitro ER activity and for mouse in vivo uterotrophic ER bindi...

  13. Human Activities in Natura 2000 Sites: A Highly Diversified Conservation Network

    Science.gov (United States)

    Tsiafouli, Maria A.; Apostolopoulou, Evangelia; Mazaris, Antonios D.; Kallimanis, Athanasios S.; Drakou, Evangelia G.; Pantis, John D.

    2013-05-01

    The Natura 2000 network was established across the European Union's (EU) Member States with the aim to conserve biodiversity, while ensuring the sustainability of human activities. However, to what kind and to what extent Natura 2000 sites are subject to human activities and how this varies across Member States remains unspecified. Here, we analyzed 111,269 human activity records from 14,727 protected sites in 20 Member States. The frequency of occurrence of activities differs among countries, with more than 86 % of all sites being subjected to agriculture or forestry. Activities like hunting, fishing, urbanization, transportation, and tourism are more frequently recorded in south European sites than in northern or eastern ones. The observed variations indicate that Natura 2000 networks are highly heterogeneous among EU Member States. Our analysis highlights the importance of agriculture in European landscapes and indicates possible targets for policy interventions at national, European, or "sub-European" level. The strong human presence in the Natura 2000 network throughout Member States, shows that conservation initiatives could succeed only by combining social and ecological sustainability and by ensuring the integration of policies affecting biodiversity.

  14. Task-free MRI predicts individual differences in brain activity during task performance.

    Science.gov (United States)

    Tavor, I; Parker Jones, O; Mars, R B; Smith, S M; Behrens, T E; Jbabdi, S

    2016-04-01

    When asked to perform the same task, different individuals exhibit markedly different patterns of brain activity. This variability is often attributed to volatile factors, such as task strategy or compliance. We propose that individual differences in brain responses are, to a large degree, inherent to the brain and can be predicted from task-independent measurements collected at rest. Using a large set of task conditions, spanning several behavioral domains, we train a simple model that relates task-independent measurements to task activity and evaluate the model by predicting task activation maps for unseen subjects using magnetic resonance imaging. Our model can accurately predict individual differences in brain activity and highlights a coupling between brain connectivity and function that can be captured at the level of individual subjects.

  15. Autocatalytic activation of the furin zymogen requires removal of the emerging enzyme's N-terminus from the active site.

    Directory of Open Access Journals (Sweden)

    Katarzyna Gawlik

    Full Text Available Before furin can act on protein substrates, it must go through an ordered process of activation. Similar to many other proteinases, furin is synthesized as a zymogen (profurin which becomes active only after the autocatalytic removal of its auto-inhibitory prodomain. We hypothesized that to activate profurin its prodomain had to be removed and, in addition, the emerging enzyme's N-terminus had to be ejected from the catalytic cleft.We constructed and analyzed the profurin mutants in which the egress of the emerging enzyme's N-terminus from the catalytic cleft was restricted. Mutants were autocatalytically processed at only the primary cleavage site Arg-Thr-Lys-Arg(107 downward arrowAsp(108, but not at both the primary and the secondary (Arg-Gly-Val-Thr-Lys-Arg(75 downward arrowSer(76 cleavage sites, yielding, as a result, the full-length prodomain and mature furins commencing from the N-terminal Asp108. These correctly processed furin mutants, however, remained self-inhibited by the constrained N-terminal sequence which continuously occupied the S' sub-sites of the catalytic cleft and interfered with the functional activity. Further, using the in vitro cleavage of the purified prodomain and the analyses of colon carcinoma LoVo cells with the reconstituted expression of the wild-type and mutant furins, we demonstrated that a three-step autocatalytic processing including the cleavage of the prodomain at the previously unidentified Arg-Leu-Gln-Arg(89 downward arrowGlu(90 site, is required for the efficient activation of furin.Collectively, our results show the restrictive role of the enzyme's N-terminal region in the autocatalytic activation mechanisms. In a conceptual form, our data apply not only to profurin alone but also to a range of self-activated proteinases.

  16. Immobilized low-activity waste site borehole 299-E17-21

    Energy Technology Data Exchange (ETDEWEB)

    Reidel, S.P.; Reynolds, K.D.; Horton, D.G.

    1998-08-01

    The Tank Waste Remediation System (TWRS) is the group at the Hanford Site responsible for the safe underground storage of liquid waste from previous Hanford Site operations, the storage and disposal of immobilized tank waste, and closure of underground tanks. The current plan is to dispose of immobilized low-activity tank waste (ILAW) in new facilities in the southcentral part of 200-East Area and in four existing vaults along the east side of 200-East Area. Boreholes 299-E17-21, B8501, and B8502 were drilled at the southwest corner of the ILAW site in support of the Performance Assessment activities for the disposal options. This report summarizes the initial geologic findings, field tests conducted on those boreholes, and ongoing studies. One deep (480 feet) borehole and two shallow (50 feet) boreholes were drilled at the southwest corner of the ILAW site. The primary factor dictating the location of the boreholes was their characterization function with respect to developing the geohydrologic model for the site and satisfying associated Data Quality Objectives. The deep borehole was drilled to characterize subsurface conditions beneath the ILAW site, and two shallow boreholes were drilled to support an ongoing environmental tracer study. The tracer study will supply information to the Performance Assessment. All the boreholes provide data on the vadose zone and saturated zone in a previously uncharacterized area.

  17. A facile reflux procedure to increase active surface sites form highly active and durable supported palladium@platinum bimetallic nanodendrites

    Science.gov (United States)

    Wang, Qin; Li, Yingjun; Liu, Baocang; Xu, Guangran; Zhang, Geng; Zhao, Qi; Zhang, Jun

    2015-11-01

    A series of well-dispersed bimetallic Pd@Pt nanodendrites uniformly supported on XC-72 carbon black are fabricated by using different capping agents. These capping agents are essential for the branched morphology control. However, the surfactant adsorbed on the nanodendrites surface blocks the access of reactant molecules to the active surface sites, and the catalytic activities of these bimetallic nanodendrites are significantly restricted. Herein, a facile reflux procedure to effectively remove the capping agent molecules without significantly affecting their sizes is reported for activating supported nanocatalysts. More significantly, the structure and morphology of the nanodendrites can also be retained, enhancing the numbers of active surface sites, catalytic activity and stability toward methanol and ethanol electro-oxidation reactions. The as-obtained hot water reflux-treated Pd@Pt/C catalyst manifests superior catalytic activity and stability both in terms of surface and mass specific activities, as compared to the untreated catalysts and the commercial Pt/C and Pd/C catalysts. We anticipate that this effective and facile removal method has more general applicability to highly active nanocatalysts prepared with various surfactants, and should lead to improvements in environmental protection and energy production.

  18. Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo

    OpenAIRE

    Kono, Mari; Tucker, Ana E.; Tran, Jennifer; Bergner, Jennifer B.; Turner, Ewa M; Proia, Richard L.

    2014-01-01

    Activation of the GPCR sphingosine-1-phosphate receptor 1 (S1P1) by sphingosine-1-phosphate (S1P) regulates key physiological processes. S1P1 activation also has been implicated in pathologic processes, including autoimmunity and inflammation; however, the in vivo sites of S1P1 activation under normal and disease conditions are unclear. Here, we describe the development of a mouse model that allows in vivo evaluation of S1P1 activation. These mice, known as S1P1 GFP signaling mice, produce a ...

  19. POISONING OF ACTIVE SITES ON ZIEGLER-NATTA CATALYST FOR PROPYLENE POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    Kitti Tangjituabun; Sang Yull Kim; Yuichi Hiraoka; Toshiaki Taniike; Minoru Terano; Bunjerd Jongsomjit; Piyasan Praserthdam

    2008-01-01

    The effects of poisoning materials on catalytic activity and isospecificity of the supported Ziegler-Natta catalyst were investigated.A minor amount of simple structure of Lewis base,i.e.,methanol,acetone,ethyl acetate,was introduced into the catalyst slurry for partial poisoning catalytic active centers.It was found that the variations in deactivation power were in the order of methanol>acetone>ethyl acetate.The kinetic investigation via stopped-flow polymerization showed that poisoning compounds caused a decrease in activity through the reduction of the number of active sites whereas no effect on the degree of isotacticity was observed.

  20. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions.

    Science.gov (United States)

    Kelly, Paul P; Eichler, Anja; Herter, Susanne; Kranz, David C; Turner, Nicholas J; Flitsch, Sabine L

    2015-01-01

    Cytochrome P450 monooxygenases are useful biocatalysts for C-H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations.

  1. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

    Directory of Open Access Journals (Sweden)

    Paul P. Kelly

    2015-09-01

    Full Text Available Cytochrome P450 monooxygenases are useful biocatalysts for C–H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations.

  2. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions.

    Science.gov (United States)

    Kelly, Paul P; Eichler, Anja; Herter, Susanne; Kranz, David C; Turner, Nicholas J; Flitsch, Sabine L

    2015-01-01

    Cytochrome P450 monooxygenases are useful biocatalysts for C-H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations. PMID:26664590

  3. Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels.

    Science.gov (United States)

    Saam, Jan; Ivanov, Igor; Walther, Matthias; Holzhütter, Hermann-Georg; Kuhn, Hartmut

    2007-08-14

    Cells contain numerous enzymes that use molecular oxygen for their reactions. Often, their active sites are buried deeply inside the protein, which raises the question whether there are specific access channels guiding oxygen to the site of catalysis. Choosing 12/15-lipoxygenase as a typical example for such oxygen-dependent enzymes, we determined the oxygen distribution within the protein and defined potential routes for oxygen access. For this purpose, we have applied an integrated strategy of structural modeling, molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements. First, we computed the 3D free-energy distribution for oxygen, which led to identification of four oxygen channels in the protein. All channels connect the protein surface with a region of high oxygen affinity at the active site. This region is localized opposite to the nonheme iron providing a structural explanation for the reaction specificity of this lipoxygenase isoform. The catalytically most relevant path can be obstructed by L367F exchange, which leads to a strongly increased Michaelis constant for oxygen. The blocking mechanism is explained in detail by reordering the hydrogen-bonding network of water molecules. Our results provide strong evidence that the main route for oxygen access to the active site of the enzyme follows a channel formed by transiently interconnected cavities whereby the opening and closure are governed by side chain dynamics. PMID:17675410

  4. Active catalytic sites in the ammoxidation of propane and propene over V-Sb-O catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, S.A.; Zanthoff, H.W. [Bochum Univ. (Germany). Lehrstuhl fuer Technische Chemie

    1998-12-31

    The ammoxidation of propane over VSb{sub y}O{sub x} catalysts (y=1, 2, 5) was investigated with respect to the role of different oxygen species in the selective and non selective reaction steps using transient experiments in the Temporal Analysis of Products (TAP) reactor. Only lattice oxygen is involved in the oxidation reactions. Using isotopic labelled oxygen it is shown that two different active sites exist on the surface. On site A, which can be reoxidized faster by gas phase oxygen compared to site B, mainly CO is formed. On site B CO{sub 2} and acrolein as well as NO and N{sub 2}O in the presence of ammonia in the feed gas are formed and reoxidation mainly occurs with bulk lattice oxygen. (orig.)

  5. Application of Artificial Intelligence to the Prediction of the Antimicrobial Activity of Essential Oils.

    Science.gov (United States)

    Daynac, Mathieu; Cortes-Cabrera, Alvaro; Prieto, Jose M

    2015-01-01

    Essential oils (EOs) are vastly used as natural antibiotics in Complementary and Alternative Medicine (CAM). Their intrinsic chemical variability and synergisms/antagonisms between its components make difficult to ensure consistent effects through different batches. Our aim is to evaluate the use of artificial neural networks (ANNs) for the prediction of their antimicrobial activity. Methods. The chemical composition and antimicrobial activity of 49 EOs, extracts, and/or fractions was extracted from NCCLS compliant works. The fast artificial neural networks (FANN) software was used and the output data reflected the antimicrobial activity of these EOs against four common pathogens: Staphylococcus aureus, Escherichia coli, Candida albicans, and Clostridium perfringens as measured by standardised disk diffusion assays. Results. ANNs were able to predict >70% of the antimicrobial activities within a 10 mm maximum error range. Similarly, ANNs were able to predict 2 or 3 different bioactivities at the same time. The accuracy of the prediction was only limited by the inherent errors of the popular antimicrobial disk susceptibility test and the nature of the pathogens. Conclusions. ANNs can be reliable, fast, and cheap tools for the prediction of the antimicrobial activity of EOs thus improving their use in CAM.

  6. Impulsive approach tendencies towards physical activity and sedentary behaviors, but not reflective intentions, prospectively predict non-exercise activity thermogenesis.

    Directory of Open Access Journals (Sweden)

    Boris Cheval

    Full Text Available Understanding the determinants of non-exercise activity thermogenesis (NEAT is crucial, given its extensive health benefits. Some scholars have assumed that a proneness to react differently to environmental cues promoting sedentary versus active behaviors could be responsible for inter-individual differences in NEAT. In line with this reflection and grounded on the Reflective-Impulsive Model, we test the assumption that impulsive processes related to sedentary and physical activity behaviors can prospectively predict NEAT, operationalized as spontaneous effort exerted to maintain low intensity muscle contractions within the release phases of an intermittent maximal isometric contraction task. Participants (n = 91 completed a questionnaire assessing their intentions to adopt physical activity behaviors and a manikin task to assess impulsive approach tendencies towards physical activity behaviors (IAPA and sedentary behaviors (IASB. Participants were then instructed to perform a maximal handgrip strength task and an intermittent maximal isometric contraction task. As hypothesized, multilevel regression analyses revealed that spontaneous effort was (a positively predicted by IAPA, (b negatively predicted by IASB, and (c was not predicted by physical activity intentions, after controlling for some confounding variables such as age, sex, usual PA level and average force provided during the maximal-contraction phases of the task. These effects remained constant throughout all the phases of the task. This study demonstrated that impulsive processes may play a unique role in predicting spontaneous physical activity behaviors. Theoretically, this finding reinforces the utility of a motivational approach based on dual-process models to explain inter-individual differences in NEAT. Implications for health behavior theories and behavior change interventions are outlined.

  7. A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations.

    Science.gov (United States)

    Schweikardt, Thorsten; Olivares, Concepción; Solano, Francisco; Jaenicke, Elmar; García-Borrón, José Carlos; Decker, Heinz

    2007-10-01

    Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase. PMID:17850513

  8. Mechanochemical coupling in the myosin motor domain. I. Insights from equilibrium active-site simulations.

    Directory of Open Access Journals (Sweden)

    Haibo Yu

    2007-02-01

    Full Text Available Although the major structural transitions in molecular motors are often argued to couple to the binding of Adenosine triphosphate (ATP, the recovery stroke in the conventional myosin has been shown to be dependent on the hydrolysis of ATP. To obtain a clearer mechanistic picture for such "mechanochemical coupling" in myosin, equilibrium active-site simulations with explicit solvent have been carried out to probe the behavior of the motor domain as functions of the nucleotide chemical state and conformation of the converter/relay helix. In conjunction with previous studies of ATP hydrolysis with different active-site conformations and normal mode analysis of structural flexibility, the results help establish an energetics-based framework for understanding the mechanochemical coupling. It is proposed that the activation of hydrolysis does not require the rotation of the lever arm per se, but the two processes are tightly coordinated because both strongly couple to the open/close transition of the active site. The underlying picture involves shifts in the dominant population of different structural motifs as a consequence of changes elsewhere in the motor domain. The contribution of this work and the accompanying paper [] is to propose the actual mechanism behind these "population shifts" and residues that play important roles in the process. It is suggested that structural flexibilities at both the small and large scales inherent to the motor domain make it possible to implement tight couplings between different structural motifs while maintaining small free-energy drops for processes that occur in the detached states, which is likely a feature shared among many molecular motors. The significantly different flexibility of the active site in different X-ray structures with variable level arm orientations supports the notation that external force sensed by the lever arm may transmit into the active site and influence the chemical steps (nucleotide

  9. Identification of canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the intracellular domain of the interleukin 23 receptor.

    Science.gov (United States)

    Floss, Doreen M; Mrotzek, Simone; Klöcker, Tobias; Schröder, Jutta; Grötzinger, Joachim; Rose-John, Stefan; Scheller, Jürgen

    2013-07-01

    Signaling of interleukin 23 (IL-23) via the IL-23 receptor (IL-23R) and the shared IL-12 receptor β1 (IL-12Rβ1) controls innate and adaptive immune responses and is involved in the differentiation and expansion of IL-17-producing CD4(+) T helper (TH17) cells. Activation of signal transducer and activator of transcription 3 (STAT3) appears to be the major signaling pathway of IL-23, and STAT binding sites were predicted in the IL-23R but not in the IL-12Rβ1 chain. Using site-directed mutagenesis and deletion variants of the murine and human IL-23R, we showed that the predicted STAT binding sites (pYXXQ; including Tyr-504 and Tyr-626 in murine IL-23R and Tyr-484 and Tyr-611 in human IL-23R) mediated STAT3 activation. Furthermore, we identified two uncommon STAT3 binding/activation sites within the murine IL-23R. First, the murine IL-23R carried the Y(542)PNFQ sequence, which acts as an unusual Src homology 2 (SH2) domain-binding protein activation site of STAT3. Second, we identified a non-canonical, phosphotyrosine-independent STAT3 activation motif within the IL-23R. A third predicted site, Tyr-416 in murine and Tyr-397 in human IL-23R, is involved in the activation of PI3K/Akt and the MAPK pathway leading to STAT3-independent proliferation of Ba/F3 cells upon stimulation with IL-23. In contrast to IL-6-induced short term STAT3 phosphorylation, cellular activation by IL-23 resulted in a slower but long term STAT3 phosphorylation, indicating that the IL-23R might not be a major target of negative feedback inhibition by suppressor of cytokine signaling (SOCS) proteins. In summary, we characterized IL-23-dependent signal transduction with a focus on STAT3 phosphorylation and identified canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the IL-23R.

  10. Structure-Functional Study of Tyrosine and Methionine Dipeptides: An Approach to Antioxidant Activity Prediction

    OpenAIRE

    Anna Torkova; Olga Koroleva; Ekaterina Khrameeva; Tatyana Fedorova; Mikhail Tsentalovich

    2015-01-01

    Quantum chemical methods allow screening and prediction of peptide antioxidant activity on the basis of known experimental data. It can be used to design the selective proteolysis of protein sources in order to obtain products with antioxidant activity. Molecular geometry and electronic descriptors of redox-active amino acids, as well as tyrosine and methionine-containing dipeptides, were studied by Density Functional Theory method. The calculated data was used to reveal several descriptors r...

  11. Early prediction of movie box office success based on Wikipedia activity big data.

    Directory of Open Access Journals (Sweden)

    Márton Mestyán

    Full Text Available Use of socially generated "big data" to access information about collective states of the minds in human societies has become a new paradigm in the emerging field of computational social science. A natural application of this would be the prediction of the society's reaction to a new product in the sense of popularity and adoption rate. However, bridging the gap between "real time monitoring" and "early predicting" remains a big challenge. Here we report on an endeavor to build a minimalistic predictive model for the financial success of movies based on collective activity data of online users. We show that the popularity of a movie can be predicted much before its release by measuring and analyzing the activity level of editors and viewers of the corresponding entry to the movie in Wikipedia, the well-known online encyclopedia.

  12. Early Prediction of Movie Box Office Success based on Wikipedia Activity Big Data

    CERN Document Server

    Mestyán, Márton; Kertész, János

    2012-01-01

    Use of socially generated "big data" to access information about collective states of the minds in human societies becomes a new paradigm in the emerging field of computational social science. One of the natural application of this would be prediction of the society's reaction to a new product in the sense of popularity and adoption rate. However, bridging between "real time monitoring" and "early predicting" remains as a big challenge. Here, we report on an endeavor to build a minimalistic predictive model for the financial success of movies based on collective activity data of online users. We show that the popularity of a movie could be predicted well in advance by measuring and analyzing the activity level of editors and viewers of the corresponding entry to the movie in Wikipedia, the well-known online encyclopedia.

  13. Identification and characterization of radioactively contaminated sites in Ukraine and planning for environmental restoration activities

    International Nuclear Information System (INIS)

    In the Pridniprovsk-Krivoy Rog region uranium, titanium, iron and manganese ores were mined and milled beginning in the 1950s. These activities have caused radioactive contamination of the environment at some sites. In recent times intensive works concerning the surveying of contaminated areas and substantiating the need for remediation have been initiated. The research methodologies applied and the results from radiation surveys are presented for the site of the first uranium mine in the Ukraine, for tailings originating from the Pridniprovsk Chemical Plant (PChP), for the recultivated dump-site of the former 'O'-mine, as well as for the wastes, raw materials and production of the Nicopol Ferro-Alloy Plant. The planning procedure for the remediation activities at the town of Zhovty Vody is described. (author)

  14. Study on the active sites of Cu-ZSM-5 in trichloroethylene catalytic combustion with air

    Institute of Scientific and Technical Information of China (English)

    Cheng Hua Xu; Chuan Qi Liu; Yan Zhong; Xiu Zhou Yang; Jian Ying Liu; Ying Chun Yang; Zhi Xiang Ye

    2008-01-01

    The catalytic activity of Cu-ZSM-5 in trichloroethylene (TCE) combustion increases with the increasing skeletal Cu amount and however decreases with the increase of surface amorphous CuO,which is detected by infrared spectroscopy (IR) and diffuse reflectance ultraviolet-visible spectroscopy (DRS-UV-vis),therefore the skeletal Cu species are concluded to be the active sites for the TCE combustion.

  15. Screening Approach to the Activation of Soil and Contamination of Groundwater at Linear Proton Accelerator Sites

    CERN Document Server

    Otto, Thomas

    The activation of soil and the contamination of groundwater at proton accelerator sites with the radionuclides 3H and 22Na are estimated with a Monte-Carlo calculation and a conservative soil- and ground water model. The obtained radionuclide concentrations show that the underground environment of future accelerators must be adequately protected against a migration of activation products. This study is of particular importance for the proton driver accelerator in the planned EURISOL facility.

  16. Variants of the cell recognition site of fibronectin that retain attachment-promoting activity

    OpenAIRE

    1985-01-01

    A tetrapeptide sequence, Arg-Gly-Asp-Ser, is the minimal structure recognized by cells in the large, adhesive glycoprotein fibronectin. We now have defined the structural requirements for this cell recognition site by testing several synthetic variants of the active tetrapeptide sequence. The conservative substitutions of lysine for arginine, alanine for glycine, or glutamic acid for aspartic acid each resulted in abrogation of the cell attachment-promoting activity characteristic of the natu...

  17. Spectroscopic studies on the active site of hydroperoxide lyase : the influence of detergents on its conformation

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Noordermeer, M.A.; Veldink, G.A.

    2001-01-01

    Expression of high quantities of alfalfa hydroperoxide lyase in Escherichia coli made it possible to study its active site and structure in more detail. Circular dichroism (CD) spectra showed that hydroperoxide lyase consists for about 75% of alpha-helices. Electron paramagnetic resonance (EPR) spec

  18. Biosynthesis of selenosubtilisin: A novel way to target selenium into the active site of subtilisin

    Institute of Scientific and Technical Information of China (English)

    LI Jing; LIU XiaoMan; JI YueTong; QI ZhenHui; GE Yan; XU JiaYun; LIU JunQiu; LUO GuiMin; SHEN JiaCong

    2008-01-01

    Glutathione peroxidase (GPx,EC1.11.1.9),an important anti-oxidative selenoenzyme,can catalyze the reduction of harmful hydroperoxides with concomitant glutathione,thereby protecting cells and other biological issues against oxidative damage.It captures considerable interest in redesign of its function for either the mechanism study or the pharmacological development as an antioxidant.In order to de-velop a general strategy for specifically targeting and operating selenium in active sites of enzymes,the catalytically essential residue selenocysteine (Sec) was first successfully bioincorporated into the catalytic center of subtilisin by using an auxotrophic expression system.The studies of the catalytic activity and the steady-state kinetics demonstrated that selenosubtilisin is an excellent GPx-like bio-catalyst.In comparison with the chemically modified method,biosynthesis exhibits obvious advan-tages:Sec could be site-directly incorporated into active sites of enzymes to overcome the non-speci-ficity generated by chemical modification.This study provides an important strategy for specifically targeting and operating selenium in the active site of an enzyme.

  19. 76 FR 51391 - Commercial Wind Lease Issuance and Site Characterization Activities on the Atlantic Outer...

    Science.gov (United States)

    2011-08-18

    ..., geotechnical, archeological, and biological surveys), and reasonably foreseeable site assessment scenarios... characterization activities (i.e., geological and geophysical surveys and core samples), a lessee must submit the results of such surveys before BOEMRE can consider its COP. See 30 CFR 285.626. 2. Proposed Action...

  20. Aberration-corrected imaging of active sites on industrial catalyst nanoparticles

    DEFF Research Database (Denmark)

    Gontard, Lionel Cervera; Chang, L-Y; Hetherington, CJD;

    2007-01-01

    Picture perfect: Information about the local topologies of active sites on commercial nanoparticles can be gained with atomic resolution through spherical-aberration-corrected transmission electron microscopy (TEM). A powder of Pt nanoparticles on carbon black was examined with two advanced TEM t...

  1. Comparative active-site mutation study of human and Caenorhabditis elegans thymidine kinase 1

    DEFF Research Database (Denmark)

    Skovgaard, Tine; Uhlin, Ulla; Munch-Petersen, Birgitte

    2012-01-01

    ligands. To improve our understanding of TK1 substrate specificity, we performed a detailed, mutation-based comparative structure-function study of the active sites of two thymidine kinases: HuTK1 and Caenorhabditis elegans TK1 (CeTK1). Specifically, mutations were introduced into the hydrophobic pocket...

  2. Molecular Interactions Between the Active Sites of RGD (Arg-Gly-Asp with its Receptor (Integrine

    Directory of Open Access Journals (Sweden)

    E. Jauregui

    2000-03-01

    Full Text Available A study of the molecular interactions between the active sites of RGD (Arg-Gly-Asp with it Receptor using simultaions is reported. Our calculations indicate that the guanidine-carboxylate complex is energetically favourd with respect to the guanidine-methyl tetrazole complex.

  3. Artificial Metalloenzymes for Asymmetric Catalysis by Creation of Novel Active Sites in Protein and DNA Scaffolds

    NARCIS (Netherlands)

    Drienovska, Ivana; Roelfes, Gerard

    2015-01-01

    Artificial metalloenzymes have emerged as a promising new approach to asymmetric catalysis. In our group, we are exploring novel artificial metalloenzyme designs involving creation of a new active site in a protein or DNA scaffold that does not have an existing binding pocket. In this review, we giv

  4. 78 FR 8190 - Commercial Wind Leasing and Site Assessment Activities on the Atlantic Outer Continental Shelf...

    Science.gov (United States)

    2013-02-05

    ... published the Notice in the Federal Register (77 FR 74218) inviting Federal, state, local government... Bureau of Ocean Energy Management Commercial Wind Leasing and Site Assessment Activities on the Atlantic... Notice of Intent to Prepare an Environmental Assessment (EA) for Commercial Wind Leasing and...

  5. 77 FR 5830 - Commercial Wind Leasing and Site Assessment Activities on the Atlantic Outer Continental Shelf...

    Science.gov (United States)

    2012-02-06

    ... (NOA) in the Federal Register (72 FR 62,672) of the Programmatic EIS for Alternative Energy Development... FR 30,616) of the EA for Issuance of Leases for Wind Resource Data Collection on the Outer... Bureau of Ocean Energy Management Commercial Wind Leasing and Site Assessment Activities on the...

  6. Domestic activities at the Linear Pottery site of Elsloo (Netherlands) : a look from under the microscoop

    NARCIS (Netherlands)

    Gijn, van A.L.; Mazzucco, N.; Hamon, C.; Allard, P.; Ilett, M.

    2013-01-01

    Use-wear analysis of a sample of flint tools from the site of Elsloo, situated in the Graetheide cluster (NL), has shed light on the domestic activities carried out within the settlement. It was shown that hide processing predominates. The extent and character of the wear on the hide working impleme

  7. Predicting the activation states of the muscles governing upper esophageal sphincter relaxation and opening.

    Science.gov (United States)

    Omari, Taher I; Jones, Corinne A; Hammer, Michael J; Cock, Charles; Dinning, Philip; Wiklendt, Lukasz; Costa, Marcello; McCulloch, Timothy M

    2016-03-15

    The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these "mechanical states" of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of "activation state" maps may allow better physiological and pathophysiological interpretations of UES function.

  8. Prediction of translation initiation sites in human mRNA sequences with AUG start codon in weak Kozak context: A neural network approach.

    Science.gov (United States)

    Tikole, Suhas; Sankararamakrishnan, Ramasubbu

    2008-05-16

    Translation of eukaryotic mRNAs is often regulated by nucleotides around the start codon. A purine at position -3 and a guanine at position +4 contribute significantly to enhance the translation efficiency. Algorithms to predict the translation initiation site often fail to predict the start site if the sequence context is not present. We have developed a neural network method to predict the initiation site of mRNA sequences that lack the preferred nucleotides at the positions -3 and +4 surrounding the translation initiation site. Neural networks of various architectures comprising different number of hidden layers were designed and tested for various sizes of windows of nucleotides surrounding translation initiation sites. We found that the neural network with two hidden layers showed a sensitivity of 83% and specificity of 73% indicating a vastly improved performance in successfully predicting the translation initiation site of mRNA sequences with weak Kozak context. WeakAUG server is freely available at http://bioinfo.iitk.ac.in/AUGPred/.

  9. Comparison between measured and predicted resting metabolic rate in moderately active adolescents.

    Science.gov (United States)

    De Lorenzo A; Bertini, I; Puijia, A; Testolin, G; Testolin, C

    1999-09-01

    The aim of this study was to check the validity of predictive equations for the calculation of resting metabolic rate (RMR) in moderately active adolescents. The RMR was measured in a sample of 25 healthy 15.5-18.2-year-old boys practicing soccer. The RMR was assessed by indirect calorimetry for 30 min following an overnight fast. Body composition was estimated from skinfold thickness measurements. Among the available equations to predict RMR, we decided to use those a of Molnar et al., Harris-Benedict, Schofield, and Cunningham. Measured and predicted values were compared by means of a one-way ANOVA. Also the Bland-Altman test was performed in order to evaluate the accuracy of the prediction equations compared to the measured value. The measured RMR was found to be 1834 +/- 160 kcal/day (mean +/- SD), while the Molnar et al., Schofield, Harris-Benedict, and Cunningham predicted values were 1707 +/- 78, 1866 +/- 89, 1779 +/- 84 and 1830 +/- 87 kcal/day, respectively. On average, compared to the measured values only the Molnar et al. equation differed significantly. On an individual basis, all the equations demonstrated considerable variability between measured and predicted RMRs. The predicted values also differed significantly. As regards the moderately active subjects (16-18 years old), we recommend the use of the Schofield equation, based on simple anthropometric parameters and also that of Cunningham, even if the estimation or measurement of fat-free mass may be cumbersome for everyday pediatric use. PMID:10664318

  10. In silico engineering and optimization of Transcription Activator-Like Effectors and their derivatives for improved DNA binding predictions.

    KAUST Repository

    Piatek, Marek J.

    2015-12-01

    Transcription Activator-Like Effectors (TALEs) can be used as adaptable DNAbinding modules to create site-specific chimeric nucleases or synthetic transcriptional regulators. The central repeat domain mediates specific DNA binding via hypervariable repeat di-residues (RVDs). This DNA-Binding Domain can be engineered to bind preferentially to any user-selected DNA sequence if engineered appropriately. Therefore, TALEs and their derivatives have become indispensable molecular tools in site-specific manipulation of genes and genomes. This thesis revolves around two problems: in silico design and improved binding site prediction of TALEs. In the first part, a study is shown where TALEs are successfully designed in silico and validated in laboratory to yield the anticipated effects on selected genes. Software is developed to accompany the process of designing and prediction of binding sites. I expanded the functionality of the software to be used as a more generic set of tools for the design, target and offtarget searching. Part two contributes a method and associated toolkit developed to allow users to design in silico optimized synthetic TALEs with user-defined specificities for various experimental purposes. This method is based on a mutual relationship of three consecutive tandem repeats in the DNA-binding domain. This approach revealed positional and compositional bias behind the binding of TALEs to DNA. In conclusion, I developed methods, approaches, and software to enhance the functionality of synthetic TALEs, which should improve understanding of TALEs biology and will further advance genome-engineering applications in various organisms and cell types.

  11. The role of the catalysts with highly dispersed and isolated active sites in the selective oxidation of light hydrocarbons

    Institute of Scientific and Technical Information of China (English)

    WANG Hongxuan; ZHAO Zhen

    2005-01-01

    This review summarizes the role of catalysts with highly dispersed and isolated active sites (active sites: supported atoms f≤0.5 % ) in the selective oxidation of light hydrocarbons, such as methane, ethane and propane, into oxygenatesand the epoxidation of olefins. The plausible structures of the highly dispersed and isolated active species, as well as their effects on the catalytic performances are discussed. The special physico-chemical properties and the functional mechanism of the catalysts with highly dispersed and isolated active sites, as well as the preparation, characterization of the catalysts with highly dispersed and isolated active sites and their applications in other types of reactions of lower hydrocarbons are summarized.

  12. Autonomous Motivation Predicts 7-Day Physical Activity in Hong Kong Students.

    Science.gov (United States)

    Ha, Amy S; Ng, Johan Y Y

    2015-07-01

    Autonomous motivation predicts positive health behaviors such as physical activity. However, few studies have examined the relation between motivational regulations and objectively measured physical activity and sedentary behaviors. Thus, we investigated whether different motivational regulations (autonomous motivation, controlled motivation, and amotivation) predicted 7-day physical activity, sedentary behaviors, and health-related quality of life (HRQoL) of students. A total of 115 students (mean age = 11.6 years, 55.7% female) self-reported their motivational regulations and health-related quality of life. Physical activity and sedentary behaviors were measured using accelerometers for seven days. Using multilevel modeling, we found that autonomous motivation predicted higher levels of moderate-to-vigorous physical activity, less sedentary behaviors, and better HRQoL. Controlled motivation and amotivation each only negatively predicted one facet of HRQoL. Results suggested that autonomous motivation could be an important predictor of physical activity behaviors in Hong Kong students. Promotion of this form of motivational regulation may also increase HRQoL.

  13. Semi-active model predictive control for 3rd generation benchmark problem using smart dampers

    Institute of Scientific and Technical Information of China (English)

    Yan Guiyun; Sun Bingnan; Lü Yanping

    2007-01-01

    A semi-active strategy for model predictive control (MPC), in which magneto-rheological dampers are used as an actuator, is presented for use in reducing the nonlinear seismic response of high-rise buildings. A multi-step predictive model is developed to estimate the seismic performance of high-rise buildings, taking into account of the effects of nonlinearity, time-variability, model mismatching, and disturbances and uncertainty of controlled system parameters by the predicted error feedback in the multi-step predictive model. Based on the predictive model, a Kalman-Bucy observer suitable for semi-active strategy is proposed to estimate the state vector from the acceleration and semi-active control force feedback.The main advantage of the proposed strategy is its inherent stability, simplicity, on-line real-time operation, and the ability to handle nonlinearity, uncertainty, and time-variability properties of structures. Numerical simulation of the nonlinear seismic responses of a controlled 20-story benchmark building is carried out, and the simulation results are compared to those of other control systems. The results show that the developed semi-active strategy can efficiently reduce the nonlinear seismic response of high-rise buildings.

  14. Asymmetry of the Active Site Loop Conformation between Subunits of Glutamate-1-semialdehyde Aminomutase in Solution

    Directory of Open Access Journals (Sweden)

    Barbara Campanini

    2013-01-01

    Full Text Available Glutamate-1-semialdehyde aminomutase (GSAM is a dimeric, pyridoxal 5′-phosphate (PLP- dependent enzyme catalysing in plants and some bacteria the isomerization of L-glutamate-1-semialdehyde to 5-aminolevulinate, a common precursor of chlorophyll, haem, coenzyme B12, and other tetrapyrrolic compounds. During the catalytic cycle, the coenzyme undergoes conversion from pyridoxamine 5′-phosphate (PMP to PLP. The entrance of the catalytic site is protected by a loop that is believed to switch from an open to a closed conformation during catalysis. Crystallographic studies indicated that the structure of the mobile loop is related to the form of the cofactor bound to the active site, allowing for asymmetry within the dimer. Since no information on structural and functional asymmetry of the enzyme in solution is available in the literature, we investigated the active site accessibility by determining the cofactor fluorescence quenching of PMP- and PLP-GSAM forms. PLP-GSAM is partially quenched by potassium iodide, suggesting that at least one catalytic site is accessible to the anionic quencher and therefore confirming the asymmetry observed in the crystal structure. Iodide induces release of the cofactor from PMP-GSAM, apparently from only one catalytic site, therefore suggesting an asymmetry also in this form of the enzyme in solution, in contrast with the crystallographic data.

  15. A split active site couples cap recognition by Dcp2 to activation

    OpenAIRE

    Floor, Stephen N.; Jones, Brittnee N.; Hernandez, Gail A.; Gross, John D.

    2010-01-01

    Decapping by Dcp2 is an essential step in 5′-3′ mRNA decay. In yeast, decapping requires an open-to-closed transition in Dcp2, though the link between closure and catalysis remains elusive. Here we show using NMR that cap binds conserved residues on both the catalytic and regulatory domains of Dcp2. Lesions in the cap-binding site on the regulatory domain reduce the catalytic step two orders of magnitude and block formation of the closed state whereas Dcp1 enhances the catalytic step by a fac...

  16. Predicting summer site occupancy for an invasive species, the common brushtail possum (Trichosurus vulpecula), in an urban environment.

    Science.gov (United States)

    Adams, Amy L; Dickinson, Katharine J M; Robertson, Bruce C; van Heezik, Yolanda

    2013-01-01

    Invasive species are often favoured in fragmented, highly-modified, human-dominated landscapes such as urban areas. Because successful invasive urban adapters can occupy habitat that is quite different from that in their original range, effective management programmes for invasive species in urban areas require an understanding of distribution, habitat and resource requirements at a local scale that is tailored to the fine-scale heterogeneity typical of urban landscapes. The common brushtail possum (Trichosurus vulpecula) is one of New Zealand's most destructive invasive pest species. As brushtail possums traditionally occupy forest habitat, control in New Zealand has focussed on rural and forest habitats, and forest fragments in cities. However, as successful urban adapters, possums may be occupying a wider range of habitats. Here we use site occupancy methods to determine the distribution of brushtail possums across five distinguishable urban habitat types during summer, which is when possums have the greatest impacts on breeding birds. We collected data on possum presence/absence and habitat characteristics, including possible sources of supplementary food (fruit trees, vegetable gardens, compost heaps), and the availability of forest fragments from 150 survey locations. Predictive distribution models constructed using the programme PRESENCE revealed that while occupancy rates were highest in forest fragments, possums were still present across a large proportion of residential habitat with occupancy decreasing as housing density increased and green cover decreased. The presence of supplementary food sources was important in predicting possum occupancy, which may reflect the high nutritional value of these food types. Additionally, occupancy decreased as the proportion of forest fragment decreased, indicating the importance of forest fragments in determining possum distribution. Control operations to protect native birds from possum predation in cities should

  17. Predicting summer site occupancy for an invasive species, the common brushtail possum (Trichosurus vulpecula, in an urban environment.

    Directory of Open Access Journals (Sweden)

    Amy L Adams

    Full Text Available Invasive species are often favoured in fragmented, highly-modified, human-dominated landscapes such as urban areas. Because successful invasive urban adapters can occupy habitat that is quite different from that in their original range, effective management programmes for invasive species in urban areas require an understanding of distribution, habitat and resource requirements at a local scale that is tailored to the fine-scale heterogeneity typical of urban landscapes. The common brushtail possum (Trichosurus vulpecula is one of New Zealand's most destructive invasive pest species. As brushtail possums traditionally occupy forest habitat, control in New Zealand has focussed on rural and forest habitats, and forest fragments in cities. However, as successful urban adapters, possums may be occupying a wider range of habitats. Here we use site occupancy methods to determine the distribution of brushtail possums across five distinguishable urban habitat types during summer, which is when possums have the greatest impacts on breeding birds. We collected data on possum presence/absence and habitat characteristics, including possible sources of supplementary food (fruit trees, vegetable gardens, compost heaps, and the availability of forest fragments from 150 survey locations. Predictive distribution models constructed using the programme PRESENCE revealed that while occupancy rates were highest in forest fragments, possums were still present across a large proportion of residential habitat with occupancy decreasing as housing density increased and green cover decreased. The presence of supplementary food sources was important in predicting possum occupancy, which may reflect the high nutritional value of these food types. Additionally, occupancy decreased as the proportion of forest fragment decreased, indicating the importance of forest fragments in determining possum distribution. Control operations to protect native birds from possum predation in

  18. Number of active transcription factor binding sites is essential for the Hes7 oscillator

    Directory of Open Access Journals (Sweden)

    de Angelis Martin

    2006-02-01

    Full Text Available Abstract Background It is commonly accepted that embryonic segmentation of vertebrates is regulated by a segmentation clock, which is induced by the cycling genes Hes1 and Hes7. Their products form dimers that bind to the regulatory regions and thereby repress the transcription of their own encoding genes. An increase of the half-life of Hes7 protein causes irregular somite formation. This was shown in recent experiments by Hirata et al. In the same work, numerical simulations from a delay differential equations model, originally invented by Lewis, gave additional support. For a longer half-life of the Hes7 protein, these simulations exhibited strongly damped oscillations with, after few periods, severely attenuated the amplitudes. In these simulations, the Hill coefficient, a crucial model parameter, was set to 2 indicating that Hes7 has only one binding site in its promoter. On the other hand, Bessho et al. established three regulatory elements in the promoter region. Results We show that – with the same half life – the delay system is highly sensitive to changes in the Hill coefficient. A small increase changes the qualitative behaviour of the solutions drastically. There is sustained oscillation and hence the model can no longer explain the disruption of the segmentation clock. On the other hand, the Hill coefficient is correlated with the number of active binding sites, and with the way in which dimers bind to them. In this paper, we adopt response functions in order to estimate Hill coefficients for a variable number of active binding sites. It turns out that three active transcription factor binding sites increase the Hill coefficient by at least 20% as compared to one single active site. Conclusion Our findings lead to the following crucial dichotomy: either Hirata's model is correct for the Hes7 oscillator, in which case at most two binding sites are active in its promoter region; or at least three binding sites are active, in which

  19. Ambulatory teaching: Do approaches to learning predict the site and preceptor characteristics valued by clerks and residents in the ambulatory setting?

    Directory of Open Access Journals (Sweden)

    Kirby John R

    2005-10-01

    Full Text Available Abstract Background In a study to determine the site and preceptor characteristics most valued by clerks and residents in the ambulatory setting we wished to confirm whether these would support effective learning. The deep approach to learning is thought to be more effective for learning than surface approaches. In this study we determined how the approaches to learning of clerks and residents predicted the valued site and preceptor characteristics in the ambulatory setting. Methods Postal survey of all medical residents and clerks in training in Ontario determining the site and preceptor characteristics most valued in the ambulatory setting. Participants also completed the Workplace Learning questionnaire that includes 3 approaches to learning scales and 3 workplace climate scales. Multiple regression analysis was used to predict the preferred site and preceptor characteristics as the dependent variables by the average scores of the approaches to learning and perception of workplace climate scales as the independent variables. Results There were 1642 respondents, yielding a 47.3% response rate. Factor analysis revealed 7 preceptor characteristics and 6 site characteristics valued in the ambulatory setting. The Deep approach to learning scale predicted all of the learners' preferred preceptor characteristics (β = 0.076 to β = 0.234, p Direction was more strongly associated with the Surface Rational approach (β = .252, p Surface Disorganized approach to learning (β = .154, p Deep approach. The Deep approach to learning scale predicted valued site characteristics of Office Management, Patient Logistics, Objectives and Preceptor Interaction (p Surface Rational approach to learning predicted valuing Learning Resources and Clinic Set-up (β = .09, p = .001; β = .197, p Surface Disorganized approach to learning weakly negatively predicted Patient Logistics (β = -.082, p = .003 and positively the Learning Resources (β = .088, p = .003. Climate

  20. Integral Public Activities as a Support to the Site Selection Process for LILW Repository

    International Nuclear Information System (INIS)

    The first site selection process for low and intermediate level radioactive waste (LILW) repository took place between 1990 and 1993 in Slovenia was stopped unsuccessfully with very strong public opposition at local level, followed by political withdrawal on national level. As one of the consequences ARAO started to develop new approach to the site selection based also on the findings from sociology, psychology and other human sciences. The recommendations on public involvement and transparency were so strong that ARAO started with first limited public relation (PR) activities which later grew to the PR process which supports all technical activities in ARAO. Presently the PR process covers communication, information and research activities and assures careful planning, prompt responds and involvement of the highest responsible persons at ARAO. Integral public relation activities are divided in several parts. Majority of activities support the on-going site selection process where activities are presently focused on functioning of local partnerships developed as a basic communication tool to involve as much citizens and public as possible on local level. Presently two local partnerships are working in Krsko and Brezice community with clear role to enhance public involvement according to Aarchus convention. Each of the partnerships is organized in a specific way adjusted to the local needs. Communication activities are organized also for different other projects and are preparing the necessary basis for the work with different groups of stake holders and in different situations. As a foundation very broad information material, such as books, leaflets, reports, magazines, video cassettes, CD and DVD on the radioactive waste management is prepared and used for different purposes. We also try to be proactive with web pages and have a well organized visitors' center. Improvement of public relation process is achieved through constant survey and feed-back information

  1. eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape

    Science.gov (United States)

    Kinoshita, Kengo; Murakami, Yoichi; Nakamura, Haruki

    2007-01-01

    We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a PDB format file as the output. In addition, the predicted interacting interface is displayed to facilitate the examination of the virtual complex structure on our own applet viewer with the web browser (URL: http://eF-site.hgc.jp/eF-seek). PMID:17567616

  2. Ionizing Groups at the Active Site of the Alkaline Phosphatase from Ostrea cucullate

    Institute of Scientific and Technical Information of China (English)

    CHEN Qiao; WANG Qin; LIAO Jinhua; CHEN Qingxi

    2006-01-01

    The ionizing groups at the active site of alkaline phosphatase (ALP, EC 3.1.3.1) from Ostrea cucullate were studied using kinetic methods. The ionization constant, pKe, of the ionizing groups at the active site of the enzyme was found to be 10.11 at 37.0℃ and the organic solvent, dioxin, had no effect on the pKe. The standard dissociation enthalpy (△Ho) was determined to be 10.57 kcal/mol (1 cal=4.18 J). The results show that the dissociation group of the enzyme active center is the з-NH3+ of lysine. Chemical modification of the enzyme by acetic anhydride and succinic anhydride demonstrates that the amino group is one of the enzyme's functional groups.

  3. Active space decomposition with multiple sites: Density matrix renormalization group algorithm

    CERN Document Server

    Parker, Shane M

    2014-01-01

    We extend the active space decomposition method, recently developed by us, to more than two active sites using the density matrix renormalization group algorithm. The fragment wave functions are described by complete or restricted active-space wave functions. Numerical results are shown on a benzene pentamer and a perylene diimide trimer. It is found that the truncation errors in our method decrease almost exponentially with respect to the number of renormalization states M, allowing for numerically exact calculations (to a few {\\mu}Eh or less) with M = 128 in both cases, which is in contrast to conventional ab initio density matrix renormalization group.

  4. Mapping Topoisomerase IV Binding and Activity Sites on the E. coli Genome.

    Science.gov (United States)

    El Sayyed, Hafez; Le Chat, Ludovic; Lebailly, Elise; Vickridge, Elise; Pages, Carine; Cornet, Francois; Cosentino Lagomarsino, Marco; Espéli, Olivier

    2016-05-01

    Catenation links between sister chromatids are formed progressively during DNA replication and are involved in the establishment of sister chromatid cohesion. Topo IV is a bacterial type II topoisomerase involved in the removal of catenation links both behind replication forks and after replication during the final separation of sister chromosomes. We have investigated the global DNA-binding and catalytic activity of Topo IV in E. coli using genomic and molecular biology approaches. ChIP-seq revealed that Topo IV interaction with the E. coli chromosome is controlled by DNA replication. During replication, Topo IV has access to most of the genome but only selects a few hundred specific sites for its activity. Local chromatin and gene expression context influence site selection. Moreover strong DNA-binding and catalytic activities are found at the chromosome dimer resolution site, dif, located opposite the origin of replication. We reveal a physical and functional interaction between Topo IV and the XerCD recombinases acting at the dif site. This interaction is modulated by MatP, a protein involved in the organization of the Ter macrodomain. These results show that Topo IV, XerCD/dif and MatP are part of a network dedicated to the final step of chromosome management during the cell cycle. PMID:27171414

  5. A Crouzon syndrome synonymous mutation activates a 5{prime} splice site within the IIIC exon of the FGFR2 gene

    Energy Technology Data Exchange (ETDEWEB)

    Gatto, F.D.; Breathnach, R. [INSERM, Nantes (France)

    1995-06-10

    Crouzon syndrome, an autosomal dominant condition causing premature fusion of cranial structures, appears to be caused by mutations in the FGFR2 gene. Several mutations have been identified in the IIIc or bek exon that alter the amino acid sequence of the receptor in a zone known to be involved in ligand binding. In addition, a synonymous G to A transition has been described in three familial Crouzon syndrome cases (mutation at the third position of the alanine 344 codon). It has been suggested that this mutation may activate a cryptic 5{prime} or 3{prime} splice site. The significance of this latter mutation in Crouzon syndrome will be established only when it is known whether it does in fact affect splicing. If it does, prediction of the structure of the mutated receptor requires us to know whether a cryptic 5{prime} or a cryptic 3{prime} splice site has been activated. Ideally, splicing of the pre-mRNA would be studied in the cell type in which the mutated receptor is supposed to exert its effect. However, in our case this information is not available. An alternative strategy is to study splicing in cultured cells using cloned genes. The validity of this approach has been established in other disease systems, for example, thalassemias. 9 refs., 1 fig.

  6. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5.

    Science.gov (United States)

    Pavri, Rushad; Gazumyan, Anna; Jankovic, Mila; Di Virgilio, Michela; Klein, Isaac; Ansarah-Sobrinho, Camilo; Resch, Wolfgang; Yamane, Arito; Reina San-Martin, Bernardo; Barreto, Vasco; Nieland, Thomas J; Root, David E; Casellas, Rafael; Nussenzweig, Michel C

    2010-10-01

    Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class switch recombination (CSR) of antibody loci. We found that Spt5, a factor associated with stalled RNA polymerase II (Pol II) and single stranded DNA (ssDNA), is required for CSR. Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II. Further, Spt5 accumulation at sites of Pol II stalling is predictive of AID-induced mutation. We propose that AID is targeted to sites of Pol II stalling in part via its association with Spt5. PMID:20887897

  7. Regulatory inspection activities on nuclear power plant sites during construction in the United Kingdom

    International Nuclear Information System (INIS)

    The work of regulatory inspection of the construction of the plant on the site is performed not only by the inspector who has been allocated to inspection duties for that site but also by the specialist staff who are involved with the safety assessment of the plant. The coordination of this work is described in the paper and examples are given of inspection activities associated with the enforcement requirements of license conditions as well as those related to the inspection of the plant itself

  8. Technical basis for classification of low-activity waste fraction from Hanford site tanks

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, C.A., Westinghouse Hanford

    1996-07-17

    The overall objective of this report is to provide a technical basis to support a U.S. Nuclear Regulatory Commission determination to classify the low-activity waste from the Hanford Site single-shell and double-shell tanks as `incidental` wastes after removal of additional radionuclides and immobilization.The proposed processing method, in addition to the previous radionuclide removal efforts, will remove the largest practical amount of total site radioactivity, attributable to high-level wastes, for disposal in a deep geologic repository. The remainder of the waste would be considered `incidental` waste and could be disposed onsite.

  9. Predicting mutually exclusive spliced exons based on exon length, splice site and reading frame conservation, and exon sequence homology

    Directory of Open Access Journals (Sweden)

    Hammesfahr Björn

    2011-06-01

    Full Text Available Abstract Background Alternative splicing of pre-mature RNA is an important process eukaryotes utilize to increase their repertoire of different protein products. Several types of different alternative splice forms exist including exon skipping, differential splicing of exons at their 3'- or 5'-end, intron retention, and mutually exclusive splicing. The latter term is used for clusters of internal exons that are spliced in a mutually exclusive manner. Results We have implemented an extension to the WebScipio software to search for mutually exclusive exons. Here, the search is based on the precondition that mutually exclusive exons encode regions of the same structural part of the protein product. This precondition provides restrictions to the search for candidate exons concerning their length, splice site conservation and reading frame preservation, and overall homology. Mutually exclusive exons that are not homologous and not of about the same length will not be found. Using the new algorithm, mutually exclusive exons in several example genes, a dynein heavy chain, a muscle myosin heavy chain, and Dscam were correctly identified. In addition, the algorithm was applied to the whole Drosophila melanogaster X chromosome and the results were compared to the Flybase annotation and an ab initio prediction. Clusters of mutually exclusive exons might be subsequent to each other and might encode dozens of exons. Conclusions This is the first implementation of an automatic search for mutually exclusive exons in eukaryotes. Exons are predicted and reconstructed in the same run providing the complete gene structure for the protein query of interest. WebScipio offers high quality gene structure figures with the clusters of mutually exclusive exons colour-coded, and several analysis tools for further manual inspection. The genome scale analysis of all genes of the Drosophila melanogaster X chromosome showed that WebScipio is able to find all but two of the 28

  10. Assessment of national systems for obtaining local acceptance of nuclear waste management siting activities

    International Nuclear Information System (INIS)

    On behalf of the United States Department of Energy (DOE), International Energy Associates Limited (IEAL) of Washington, D.C. has conducted surveys and analyses of fourteen countries' plans and approaches for dealing with the problems of obtaining local siting acceptance for nuclear waste management facilities. It was determined that the following elements of the formal systems generally facilitate and/or expedite waste management siting decisions: (1) a clear-cut pro-nuclear power position on the part of the government; (2) a willingness on the part of the central government to exert (with prudence and restraint) its pre-emptive rights in nuclear matters; (3) political structures in which the heads of regional or provincial governments are appointed by the central government; (4) national laws that link reactor licensing with a detailed plan for waste management; (5) an established and stable policy with regard to reprocessing. In contrast, it was determined that the following elements of the formal system generally hinder waste management siting activities: (1) historically strong local land used veto laws; (2) the use of national referenda for making nuclear decisions; (3) requirements for public hearings. The informal approaches fall into the following five categories: (1) political: e.g. assertion of will by political leaders, activities to enlist support of local politicians, activities to broaden involvement in decision-making; (2) economic: e.g. emphasis on normal benefits, provision for additional economic benefits; (3) siting: e.g. at or near existing nuclear facilities, on government or utility property, at multiple locations to spread the political burden; (4) timing: e.g. decoupling drilling activities from ultimate repository site decision, deliberate deferral to (long-range) future; (5) education: e.g. creation of special government programmes, enlisting of media support

  11. Kinetic model of ethopropazine interaction with horse serum butyrylcholinesterase and its docking into the active site.

    Science.gov (United States)

    Golicnik, Marko; Sinko, Goran; Simeon-Rudolf, Vera; Grubic, Zoran; Stojan, Jure

    2002-02-01

    The action of a potent tricyclic cholinesterase inhibitor ethopropazine on the hydrolysis of acetylthiocholine and butyrylthiocholine by purified horse serum butyrylcholinesterase (EC 3.1.1.8) was investigated at 25 and 37 degrees C. The enzyme activities were measured on a stopped-flow apparatus and the analysis of experimental data was done by applying a six-parameter model for substrate hydrolysis. The model, which was introduced to explain the kinetics of Drosophila melanogaster acetylcholinesterase [Stojan et al. (1998) FEBS Lett. 440, 85-88], is defined with two dissociation constants and four rate constants and can describe both cooperative phenomena, apparent activation at low substrate concentrations and substrate inhibition by excess of substrate. For the analysis of the data in the presence of ethopropazine at two temperatures, we have enlarged the reaction scheme to allow primarily its competition with the substrate at the peripheral site, but the competition at the acylation site was not excluded. The proposed reaction scheme revealed, upon analysis, competitive effects of ethopropazine at both sites; at 25 degrees C, three enzyme-inhibitor dissociation constants could be evaluated; at 37 degrees C, only two constants could be evaluated. Although the model considers both cooperative phenomena, it appears that decreased enzyme sensitivity at higher temperature, predominantly for the ligands at the peripheral binding site, makes the determination of some expected enzyme substrate and/or inhibitor complexes technically impossible. The same reason might also account for one of the paradoxes in cholinesterases: activities at 25 degrees C at low substrate concentrations are higher than at 37 degrees C. Positioning of ethopropazine in the active-site gorge by molecular dynamics simulations shows that A328, W82, D70, and Y332 amino acid residues stabilize binding of the inhibitor. PMID:11811945

  12. Controlling activation site density by low-energy far-field stimulation in cardiac tissue

    Science.gov (United States)

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2012-06-01

    Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites (“virtual electrodes”) in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

  13. Black and Brown Bear Activity at Selected Coastal Sites in Glacier Bay National Park and Preserve, Alaska: A Preliminary Assessment Using Noninvasive Procedures

    Science.gov (United States)

    Partridge, Steve; Smith, Tom; Lewis, Tania

    2009-01-01

    A number of efforts in recent years have sought to predict bear activity in various habitats to minimize human disturbance and bear/human conflicts. Alaskan coastal areas provide important foraging areas for bears (Ursus americanus and U. arctos), particularly following den emergence when there may be no snow-free foraging alternatives. Additionally, coastal areas provide important food items for bears throughout the year. Glacier Bay National Park and Preserve (GLBA) in southeastern Alaska has extensive coastal habitats, and the National Park Service (NPS) has been long interested in learning more about the use of these coastal habitats by bears because these same habitats receive extensive human use by park visitors, especially kayaking recreationists. This study provides insight regarding the nature and intensity of bear activity at selected coastal sites within GLBA. We achieved a clearer understanding of bear/habitat relationships within GLBA by analyzing bear activity data collected with remote cameras, bear sign mapping, scat collections, and genetic analysis of bear hair. Although we could not quantify actual levels of bear activity at study sites, agreement among measures of activity (for example, sign counts, DNA analysis, and video record) lends support to our qualitative site assessments. This work suggests that habitat evaluation, bear sign mapping, and periodic scat counts can provide a useful index of bear activity for sites of interest.

  14. Development of a regression model to predict copper toxicity to Daphnia magna and site-specific copper criteria across multiple surface-water drainages in an arid landscape.

    Science.gov (United States)

    Fulton, Barry A; Meyer, Joseph S

    2014-08-01

    The water effect ratio (WER) procedure developed by the US Environmental Protection Agency is commonly used to derive site-specific criteria for point-source metal discharges into perennial waters. However, experience is limited with this method in the ephemeral and intermittent systems typical of arid climates. The present study presents a regression model to develop WER-based site-specific criteria for a network of ephemeral and intermittent streams influenced by nonpoint sources of Cu in the southwestern United States. Acute (48-h) Cu toxicity tests were performed concurrently with Daphnia magna in site water samples and hardness-matched laboratory waters. Median effect concentrations (EC50s) for Cu in site water samples (n=17) varied by more than 12-fold, and the range of calculated WER values was similar. Statistically significant (α=0.05) univariate predictors of site-specific Cu toxicity included (in sequence of decreasing significance) dissolved organic carbon (DOC), hardness/alkalinity ratio, alkalinity, K, and total dissolved solids. A multiple-regression model developed from a combination of DOC and alkalinity explained 85% of the toxicity variability in site water samples, providing a strong predictive tool that can be used in the WER framework when site-specific criteria values are derived. The biotic ligand model (BLM) underpredicted toxicity in site waters by more than 2-fold. Adjustments to the default BLM parameters improved the model's performance but did not provide a better predictive tool compared with the regression model developed from DOC and alkalinity.

  15. On the development of a model predicting the recrystallization texture of aluminum using the Taylor model for rolling textures and the coincidence lattice site theory

    Science.gov (United States)

    T, Morimoto; F, Yoshida; A, Yanagida; J, Yanagimoto

    2015-04-01

    First, hardening model in f.c.c. metals was formulated with collinear interactions slips, Hirth slips and Lomer-Cottrell slips. Using the Taylor and the Sachs rolling texture prediction model, the residual dislocation densities of cold-rolled commercial pure aluminum were estimated. Then, coincidence site lattice grains were investigated from observed cold rolling texture. Finally, on the basis of oriented nucleation theory and coincidence site lattice theory, the recrystallization texture of commercial pure aluminum after low-temperature annealing was predicted.

  16. eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape

    OpenAIRE

    Kinoshita, Kengo; Murakami, Yoichi; Nakamura, Haruki

    2007-01-01

    We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a ...

  17. Predikin and PredikinDB: a computational framework for the prediction of protein kinase peptide specificity and an associated database of phosphorylation sites

    OpenAIRE

    Kemp Bruce E; Huber Thomas; Brinkworth Ross I; Saunders Neil FW; Kobe Bostjan

    2008-01-01

    Abstract Background We have previously described an approach to predicting the substrate specificity of serine-threonine protein kinases. The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. Predikin was implemented originally as a web application written in Javascript. Results Here, we describe a...

  18. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Science.gov (United States)

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). PMID:26544602

  19. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Science.gov (United States)

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01).

  20. Neural Activities Underlying the Feedback Express Salience Prediction Errors for Appetitive and Aversive Stimuli

    Science.gov (United States)

    Gu, Yan; Hu, Xueping; Pan, Weigang; Yang, Chun; Wang, Lijun; Li, Yiyuan; Chen, Antao

    2016-01-01

    Feedback information is essential for us to adapt appropriately to the environment. The feedback-related negativity (FRN), a frontocentral negative deflection after the delivery of feedback, has been found to be larger for outcomes that are worse than expected, and it reflects a reward prediction error derived from the midbrain dopaminergic projections to the anterior cingulate cortex (ACC), as stated in reinforcement learning theory. In contrast, the prediction of response-outcome (PRO) model claims that the neural activity in the mediofrontal cortex (mPFC), especially the ACC, is sensitive to the violation of expectancy, irrespective of the valence of feedback. Additionally, increasing evidence has demonstrated significant activities in the striatum, anterior insula and occipital lobe for unexpected outcomes independently of their valence. Thus, the neural mechanism of the feedback remains under dispute. Here, we investigated the feedback with monetary reward and electrical pain shock in one task via functional magnetic resonance imaging. The results revealed significant prediction-error-related activities in the bilateral fusiform gyrus, right middle frontal gyrus and left cingulate gyrus for both money and pain. This implies that some regions underlying the feedback may signal a salience prediction error rather than a reward prediction error. PMID:27694920