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Sample records for 3d qsar analysis

  1. Alignment-independent technique for 3D QSAR analysis.

    PubMed

    Wilkes, Jon G; Stoyanova-Slavova, Iva B; Buzatu, Dan A

    2016-04-01

    Molecular biochemistry is controlled by 3D phenomena but structure-activity models based on 3D descriptors are infrequently used for large data sets because of the computational overhead for determining molecular conformations. A diverse dataset of 146 androgen receptor binders was used to investigate how different methods for defining molecular conformations affect the performance of 3D-quantitative spectral data activity relationship models. Molecular conformations tested: (1) global minimum of molecules' potential energy surface; (2) alignment-to-templates using equal electronic and steric force field contributions; (3) alignment using contributions "Best-for-Each" template; (4) non-energy optimized, non-aligned (2D > 3D). Aggregate predictions from models were compared. Highest average coefficients of determination ranged from R Test (2) = 0.56 to 0.61. The best model using 2D > 3D (imported directly from ChemSpider) produced R Test (2) = 0.61. It was superior to energy-minimized and conformation-aligned models and was achieved in only 3-7 % of the time required using the other conformation strategies. Predictions averaged from models built on different conformations achieved a consensus R Test (2) = 0.65. The best 2D > 3D model was analyzed for underlying structure-activity relationships. For the compound strongest binding to the androgen receptor, 10 substructural features contributing to binding were flagged. Utility of 2D > 3D was compared for two other activity endpoints, each modeling a medium sized data set. Results suggested that large scale, accurate predictions using 2D > 3D SDAR descriptors may be produced for interactions involving endocrine system nuclear receptors and other data sets in which strongest activities are produced by fairly inflexible substrates.

  2. Molecular Determinants of Juvenile Hormone Action as Revealed by 3D QSAR Analysis in Drosophila

    PubMed Central

    Beňo, Milan; Farkaš, Robert

    2009-01-01

    Background Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH). While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. Methodology/Principal Findings To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen) at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 Å or longer than 13.5 Å, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. Conclusions/Significance The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions. PMID:19547707

  3. QSAR and 3D QSAR of inhibitors of the epidermal growth factor receptor

    NASA Astrophysics Data System (ADS)

    Pinto-Bazurco, Mariano; Tsakovska, Ivanka; Pajeva, Ilza

    This article reports quantitative structure-activity relationships (QSAR) and 3D QSAR models of 134 structurally diverse inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase. Free-Wilson analysis was used to derive the QSAR model. It identified the substituents in aniline, the polycyclic system, and the substituents at the 6- and 7-positions of the polycyclic system as the most important structural features. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used in the 3D QSAR modeling. The steric and electrostatic interactions proved the most important for the inhibitory effect. Both QSAR and 3D QSAR models led to consistent results. On the basis of the statistically significant models, new structures were proposed and their inhibitory activities were predicted.

  4. Combinatorial Pharmacophore-Based 3D-QSAR Analysis and Virtual Screening of FGFR1 Inhibitors

    PubMed Central

    Zhou, Nannan; Xu, Yuan; Liu, Xian; Wang, Yulan; Peng, Jianlong; Luo, Xiaomin; Zheng, Mingyue; Chen, Kaixian; Jiang, Hualiang

    2015-01-01

    The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays crucial roles in cell proliferation, angiogenesis, migration, and survival. Aberration in FGFRs correlates with several malignancies and disorders. FGFRs have proved to be attractive targets for therapeutic intervention in cancer, and it is of high interest to find FGFR inhibitors with novel scaffolds. In this study, a combinatorial three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed based on previously reported FGFR1 inhibitors with diverse structural skeletons. This model was evaluated for its prediction performance on a diverse test set containing 232 FGFR inhibitors, and it yielded a SD value of 0.75 pIC50 units from measured inhibition affinities and a Pearson’s correlation coefficient R2 of 0.53. This result suggests that the combinatorial 3D-QSAR model could be used to search for new FGFR1 hit structures and predict their potential activity. To further evaluate the performance of the model, a decoy set validation was used to measure the efficiency of the model by calculating EF (enrichment factor). Based on the combinatorial pharmacophore model, a virtual screening against SPECS database was performed. Nineteen novel active compounds were successfully identified, which provide new chemical starting points for further structural optimization of FGFR1 inhibitors. PMID:26110383

  5. Combinatorial Pharmacophore-Based 3D-QSAR Analysis and Virtual Screening of FGFR1 Inhibitors.

    PubMed

    Zhou, Nannan; Xu, Yuan; Liu, Xian; Wang, Yulan; Peng, Jianlong; Luo, Xiaomin; Zheng, Mingyue; Chen, Kaixian; Jiang, Hualiang

    2015-06-11

    The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays crucial roles in cell proliferation, angiogenesis, migration, and survival. Aberration in FGFRs correlates with several malignancies and disorders. FGFRs have proved to be attractive targets for therapeutic intervention in cancer, and it is of high interest to find FGFR inhibitors with novel scaffolds. In this study, a combinatorial three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed based on previously reported FGFR1 inhibitors with diverse structural skeletons. This model was evaluated for its prediction performance on a diverse test set containing 232 FGFR inhibitors, and it yielded a SD value of 0.75 pIC50 units from measured inhibition affinities and a Pearson's correlation coefficient R2 of 0.53. This result suggests that the combinatorial 3D-QSAR model could be used to search for new FGFR1 hit structures and predict their potential activity. To further evaluate the performance of the model, a decoy set validation was used to measure the efficiency of the model by calculating EF (enrichment factor). Based on the combinatorial pharmacophore model, a virtual screening against SPECS database was performed. Nineteen novel active compounds were successfully identified, which provide new chemical starting points for further structural optimization of FGFR1 inhibitors.

  6. 3D-QSAR and 3D-QSSR studies of thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as CDK4 inhibitors by CoMFA analysis

    PubMed Central

    Cai, Bao-qin; Jin, Hai-xiao; Yan, Xiao-jun; Zhu, Peng; Hu, Gui-xiang

    2014-01-01

    Aim: To investigate the structural basis underlying potency and selectivity of a series of novel analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones as cyclin-dependent kinase 4 (CDK4) inhibitors and to use this information for drug design strategies. Methods: Three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models using comparative molecular field analysis (CoMFA) were conducted on a training set of 48 compounds. Partial least squares (PLS) analysis was employed. External validation was performed with a test set of 9 compounds. Results: The obtained 3D-QSAR model (q2=0.724, r2=0.965, r2pred=0.945) and 3D-QSSR model (q2=0.742, r2=0.923, r2pred=0.863) were robust and predictive. Contour maps with good compatibility to active binding sites provided insight into the potentially important structural features required to enhance activity and selectivity. The contour maps indicated that bulky groups at R1 position could potentially enhance CDK4 inhibitory activity, whereas bulky groups at R3 position have the opposite effect. Appropriate incorporation of bulky electropositive groups at R4 position is favorable and could improve both potency and selectivity to CDK4. Conclusion: These two models provide useful information to guide drug design strategies aimed at obtaining potent and selective CDK4 inhibitors. PMID:24122012

  7. 3D-QSAR AND CONTOUR MAP ANALYSIS OF TARIQUIDAR ANALOGUES AS MULTIDRUG RESISTANCE PROTEIN-1 (MRP1) INHIBITORS

    PubMed Central

    Kakarla, Prathusha; Inupakutika, Madhuri; Devireddy, Amith R.; Gunda, Shravan Kumar; Willmon, Thomas Mark; Ranjana, KC; Shrestha, Ugina; Ranaweera, Indrika; Hernandez, Alberto J.; Barr, Sharla; Varela, Manuel F.

    2016-01-01

    One of the major obstacles to the successful chemotherapy towards several cancers is multidrug resistance of human cancer cells to anti-cancer drugs. An important contributor to multidrug resistance is the human multidrug resistance protein-1 transporter (MRP1), which is an efflux pump of the ABC (ATP binding cassette) superfamily. Thus, highly efficacious, third generation MRP1 inhibitors, like tariquidar analogues, are promising inhibitors of multidrug resistance and are under clinical trials. To maximize the efficacy of MRP1 inhibitors and to reduce systemic toxicity, it is important to limit the exposure of MRP1 inhibitors and anticancer drugs to normal tissues and to increase their co-localization with tumor cells. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) associated with 3D-Quantitiative structure-activity relationship (3D-QSAR) studies were performed on a series of tariquidar analogues, as selective MDR modulators. Best predictability was obtained with CoMFA model r2(non-cross-validated square of correlation coefficient) = 0.968, F value = 151.768 with five components, standard error of estimate = 0.107 while the CoMSIA yielded r2 = 0.982, F value = 60.628 with six components, and standard error of estimate = 0.154. These results indicate that steric, electrostatic, hydrophobic (lipophilic), and hydrogen bond donor substituents play significant roles in multidrug resistance modulation of tariquidar analogues upon MRP1. The tariquidar analogue and MRP1 binding and stability data generated from CoMFA and CoMSIA based 3D–contour maps may further aid in study and design of tariquidar analogues as novel, potent and selective MDR modulator drug candidates. PMID:26913287

  8. Novel substituted benzothiophene and thienothiophene carboxanilides and quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor evaluation and 3D-derived QSAR analysis.

    PubMed

    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Uzelac, Lidija; Jarak, Ivana; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Kralj, Marijeta; Tomić, Sanja; Karminski-Zamola, Grace

    2012-06-14

    A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides and benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Highly predictive 3D-derived QSAR models were obtained, and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D-QSAR analysis. Taken together, the results indicate which modifications of the compounds from the series should further improve their anticancer properties.

  9. Comparison of steroid substrates and inhibitors of P-glycoprotein by 3D-QSAR analysis

    NASA Astrophysics Data System (ADS)

    Li, Yan; Wang, Yong-Hua; Yang, Ling; Zhang, Shu-Wei; Liu, Chang-Hou; Yang, Sheng-Li

    2005-01-01

    Steroid derivatives show a complex interaction with P-glycoprotein (Pgp). To determine the essential structural requirements of a series of structurally related and functionally diverse steroids for Pgp-mediated transport or inhibition, a three-dimensional quantitative structure activity relationship study was performed by comparative similarity index analysis modeling. Twelve models have been explored to well correlate the physiochemical features with their biological functions with Pgp on basis of substrate and inhibitor datasets, in which the best predictive model for substrate gave cross-validated q2=0.720, non-cross-validated r2=0.998, standard error of estimate SEE=0.012, F=257.955, and the best predictive model for inhibitor gave q2=0.536, r2=0.950, SEE=1.761 and F=45.800. The predictive ability of all models was validated by a set of compounds that were not included in the training set. The physiochemical similarities and differences of steroids as Pgp substrate and inhibitor, respectively, were analyzed to be helpful in developing new steroid-like compounds.

  10. Receptor-based 3D-QSAR in Drug Design: Methods and Applications in Kinase Studies.

    PubMed

    Fang, Cheng; Xiao, Zhiyan

    2016-01-01

    Receptor-based 3D-QSAR strategy represents a superior integration of structure-based drug design (SBDD) and three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. It combines the accurate prediction of ligand poses by the SBDD approach with the good predictability and interpretability of statistical models derived from the 3D-QSAR approach. Extensive efforts have been devoted to the development of receptor-based 3D-QSAR methods and two alternative approaches have been exploited. One associates with computing the binding interactions between a receptor and a ligand to generate structure-based descriptors for QSAR analyses. The other concerns the application of various docking protocols to generate optimal ligand poses so as to provide reliable molecular alignments for the conventional 3D-QSAR operations. This review highlights new concepts and methodologies recently developed in the field of receptorbased 3D-QSAR, and in particular, covers its application in kinase studies.

  11. Molecular modeling, quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT1 and ETA receptor antagonists

    PubMed Central

    Singh, Khuraijam Dhanachandra; Muthusamy, Karthikeyan

    2013-01-01

    Aim: Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods: Molecular modeling approach combining quantum-polarized ligand docking (QPLD), MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results: 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship: substitution of methoxymethyl and cyclooctanone might increase the activity against AT1 receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT1 receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion: This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are

  12. 3D-QSAR - Applications, Recent Advances, and Limitations

    NASA Astrophysics Data System (ADS)

    Sippl, Wolfgang

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques are the most prominent computational means to support chemistry within drug design projects where no three-dimensional structure of the macromolecular target is available. The primary aim of these techniques is to establish a correlation of biological activities of a series of structurally and biologically characterized compounds with the spatial fingerprints of numerous field properties of each molecule, such as steric demand, lipophilicity, and electrostatic interactions. The number of 3D-QSAR studies has exponentially increased over the last decade, since a variety of methods are commercially available in user-friendly, graphically guided software. In this chapter, we will review recent advances, known limitations, and the application of receptor-based 3D-QSAR

  13. Integrated computational tools for identification of CCR5 antagonists as potential HIV-1 entry inhibitors: homology modeling, virtual screening, molecular dynamics simulations and 3D QSAR analysis.

    PubMed

    Moonsamy, Suri; Dash, Radha Charan; Soliman, Mahmoud E S

    2014-04-23

    Using integrated in-silico computational techniques, including homology modeling, structure-based and pharmacophore-based virtual screening, molecular dynamic simulations, per-residue energy decomposition analysis and atom-based 3D-QSAR analysis, we proposed ten novel compounds as potential CCR5-dependent HIV-1 entry inhibitors. Via validated docking calculations, binding free energies revealed that novel leads demonstrated better binding affinities with CCR5 compared to maraviroc, an FDA-approved HIV-1 entry inhibitor and in clinical use. Per-residue interaction energy decomposition analysis on the averaged MD structure showed that hydrophobic active residues Trp86, Tyr89 and Tyr108 contributed the most to inhibitor binding. The validated 3D-QSAR model showed a high cross-validated rcv2 value of 0.84 using three principal components and non-cross-validated r2 value of 0.941. It was also revealed that almost all compounds in the test set and training set yielded a good predicted value. Information gained from this study could shed light on the activity of a new series of lead compounds as potential HIV entry inhibitors and serve as a powerful tool in the drug design and development machinery.

  14. 3D-Pharmacophore Mapping Using 4D-QSAR Analysis for the Cytotoxicity of Lamellarins Against Human Hormone-Dependent T47D Breast Cancer Cells

    PubMed Central

    Thipnate, Poonsiri; Liu, Jianzhong; Hannongbua, Supa; Hopfinger, A. J.

    2009-01-01

    4D-QSAR and 3D-pharmacophore models were built and investigated for the cytotoxicity using a training set of 25 lamellarins against human hormone dependent T47D breast cancer cells. Receptor-independent (RI) 4D-QSAR models were first constructed from the exploration of eight possible receptor binding alignments for the entire training set. Since the training set is small (25 compounds), the generality of the 4D-QSAR paradigm was then exploited to devise a strategy to maximize the extraction of binding information from the training set, and to also permit virtual screening of diverse lamellarin chemistry. 4D-QSAR models were sought for only six of the most potent lamellarins of the training set as well as another subset composed of lamellarins with constrained ranges in molecular weight and lipophilicty. This overall modeling strategy has permitted maximizing 3D-pharmacophore information from this small set of structurally complex lamellarins that can be used to drive future analog synthesis and the selection of alternate scaffolds. Overall, it was found that formation of an intermolecular hydrogen bond and hydrophobic interactions for substituents on the E ring most modulate the cytotoxicity against T47D breast cancer cells. Hydrophobic substitutions on the F-ring can also enhance cytotoxic potency. A complementary high throughput virtual screen to the 3D-pharmacophore models, a 4D-fingerprint QSAR model, was constructed using absolute molecular similarity. This 4D-fingerprint virtual high throughput screen permits a larger range of chemistry diversity to be assayed than the 4D-QSAR models. The optimized 4D-QSAR 3D-pharmacophore model has a LOO cross-correlation value of xv-r2 = 0.947, while the optimized 4D-fingerprint virtual screening model has a value of xv-r2 = 0.719. This work reveals that it is possible to develop significant QSAR, 3D-pharmacophore and virtual screening models for a small set of lamellarins showing cytotoxic behavior in breast cancer screens

  15. Structural requirements of 3-carboxyl-4(1H)-quinolones as potential antimalarials from 2D and 3D QSAR analysis.

    PubMed

    Li, Jiazhong; Li, Shuyan; Bai, Chongliang; Liu, Huanxiang; Gramatica, Paola

    2013-07-01

    Malaria is a fatal tropical and subtropical disease caused by the protozoal species Plasmodium. Many commonly available antimalarial drugs and therapies are becoming ineffective because of the emergence of multidrug resistant Plasmodium falciparum, which drives the need for the development of new antimalarial drugs. Recently, a series of 3-carboxyl-4(1H)-quinolone analogs, derived from the famous compound endochin, were reported as promising candidates for orally efficacious antimalarials. In this study, to analyze the structure-activity relationships (SAR) of these quinolones and investigate the structural requirements for antimalarial activity, the 2D multiple linear regressions (MLR) method and 3D comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods are employed to evolve different QSAR models. All these models give satisfactory results with highly accurate fitting and strong external predictive abilities for chemicals not used in model development. Furthermore, the contour maps from 3D models can provide an intuitive understanding of the key structure features responsible for the antimalarial activities. In conclusion, we summarize the detailed position-specific structural requirements of these derivatives accordingly. All these results are helpful for the rational design of new compounds with higher antimalarial bioactivities.

  16. Neuronal nicotinic acetylcholine receptor agonists: pharmacophores, evolutionary QSAR and 3D-QSAR models.

    PubMed

    Nicolotti, Orazio; Altomare, Cosimo; Pellegrini-Calace, Marialuisa; Carotti, Angelo

    2004-01-01

    Neuronal nicotinic acetylcholine ion channel receptors (nAChRs) exist as several subtypes and are involved in a variety of functions and disorders of the central nervous system (CNS), such as Alzheimer's and Parkinson's diseases. The lack of reliable information on the 3D structure of nAChRs prompted us to focus efforts on pharmacophore and structure-affinity relationships (SAFIRs). The use of DISCO (DIStance COmparison) and Catalyst/HipHop led to the formulation of a pharmacophore that is made of three geometrically unrelated features: (i) an ammonium head involved in coulombic and/or H-bond interactions, (ii) a lone pair of a pyridine nitrogen or a carbonyl oxygen, as H-bond acceptor site, and (iii) a hydrophobic molecular region generally constituted by aliphatic cycles. The quantitative SAFIR (QSAFIR) study was carried out on about three hundred nicotinoid agonists, and coherent results were obtained from classical Hansch-type approach, 3D QSAFIRs, based on Comparative Molecular Field Analysis (CoMFA), and trade-off models generated by Multi-objective Genetic QSAR (MoQSAR), a novel evolutionary software that makes use of Genetic Programming (GP) and multi-objective optimization (MO). Within each congeneric series, Hansch-type equations revealed detrimental steric effects as the major factors modulating the receptor affinity, whereas CoMFA allowed us to merge progressively single-class models in a more global one, whose robustness was supported by crossvalidation, high prediction statistics and satisfactory predictions of the affinity data of a true external ligand set (r(2)(pred) = 0.796). Next, MoQSAR was used to analyze a data set of 58 highly active nicotinoids characterized by 56 descriptors, that are log P, MR and 54 low inter-correlated WHIM (Weighted Holistic Invariant Molecular) indices. Equivalent QSAFIR models, that represent different compromises between structural model complexity, fitting and internal model complexity, were found. Our attention was

  17. Neuronal nicotinic acetylcholine receptor agonists: pharmacophores, evolutionary QSAR and 3D-QSAR models.

    PubMed

    Nicolotti, Orazio; Altomare, Cosimo; Pellegrini-Calace, Marialuisa; Carotti, Angelo

    2004-01-01

    Neuronal nicotinic acetylcholine ion channel receptors (nAChRs) exist as several subtypes and are involved in a variety of functions and disorders of the central nervous system (CNS), such as Alzheimer's and Parkinson's diseases. The lack of reliable information on the 3D structure of nAChRs prompted us to focus efforts on pharmacophore and structure-affinity relationships (SAFIRs). The use of DISCO (DIStance COmparison) and Catalyst/HipHop led to the formulation of a pharmacophore that is made of three geometrically unrelated features: (i) an ammonium head involved in coulombic and/or H-bond interactions, (ii) a lone pair of a pyridine nitrogen or a carbonyl oxygen, as H-bond acceptor site, and (iii) a hydrophobic molecular region generally constituted by aliphatic cycles. The quantitative SAFIR (QSAFIR) study was carried out on about three hundred nicotinoid agonists, and coherent results were obtained from classical Hansch-type approach, 3D QSAFIRs, based on Comparative Molecular Field Analysis (CoMFA), and trade-off models generated by Multi-objective Genetic QSAR (MoQSAR), a novel evolutionary software that makes use of Genetic Programming (GP) and multi-objective optimization (MO). Within each congeneric series, Hansch-type equations revealed detrimental steric effects as the major factors modulating the receptor affinity, whereas CoMFA allowed us to merge progressively single-class models in a more global one, whose robustness was supported by crossvalidation, high prediction statistics and satisfactory predictions of the affinity data of a true external ligand set (r(2)(pred) = 0.796). Next, MoQSAR was used to analyze a data set of 58 highly active nicotinoids characterized by 56 descriptors, that are log P, MR and 54 low inter-correlated WHIM (Weighted Holistic Invariant Molecular) indices. Equivalent QSAFIR models, that represent different compromises between structural model complexity, fitting and internal model complexity, were found. Our attention was

  18. Structure/response correlations and similarity/diversity analysis by GETAWAY descriptors. 2. Application of the novel 3D molecular descriptors to QSAR/QSPR studies.

    PubMed

    Consonni, Viviana; Todeschini, Roberto; Pavan, Manuela; Gramatica, Paola

    2002-01-01

    In a previous paper the theory of the new molecular descriptors called GETAWAY (GEometry, Topology, and Atom-Weights AssemblY) was explained. These descriptors have been proposed with the aim of matching 3D-molecular geometry, atom relatedness, and chemical information. In this paper prediction ability in structure-property correlations of GETAWAY descriptors has been tested extensively by analyzing the regressions of these descriptors for selected properties of some reference compound classes. Moreover, the general performance of the new descriptors in QSAR/QSPR has been evaluated with respect to other well-known sets of molecular descriptors.

  19. Synthesis, 3D-QSAR analysis and biological evaluation of quinoxaline 1,4-di-N-oxide derivatives as antituberculosis agents.

    PubMed

    Pan, Yuanhu; Li, Panpan; Xie, Shuyu; Tao, Yanfei; Chen, Dongmei; Dai, Menghong; Hao, Haihong; Huang, Lingli; Wang, Yulian; Wang, Liye; Liu, Zhenli; Yuan, Zonghui

    2016-08-15

    A series of quinoxaline 1,4-di-N-oxide derivatives variously substituted at C-2 position were synthesized and evaluated for in vitro antimycobacterial activity. Seventeen compounds exhibited potential activity (MIC ⩽6.25μg/mL) against Mycobacterium tuberculosis (H37Rv), in particular the compounds 3d and 3j having an MIC value of 0.39μg/mL. None of the compounds exhibited cytotoxicity when using an MTT assay in VERO cells. To further investigate the structure-activity relationship, CoMFA (q(2)=0.507, r(2)=0.923) and CoMSIA (q(2)=0.665, r(2)=0.977) models were performed on the basis of antimycobacterial activity data. The 3D-QSAR study of these compounds can provide useful information for further rational design of novel quinoxaline 1,4-di-N-oxides for treatment of tuberculosis. PMID:27426298

  20. Synthesis, 3D-QSAR analysis and biological evaluation of quinoxaline 1,4-di-N-oxide derivatives as antituberculosis agents.

    PubMed

    Pan, Yuanhu; Li, Panpan; Xie, Shuyu; Tao, Yanfei; Chen, Dongmei; Dai, Menghong; Hao, Haihong; Huang, Lingli; Wang, Yulian; Wang, Liye; Liu, Zhenli; Yuan, Zonghui

    2016-08-15

    A series of quinoxaline 1,4-di-N-oxide derivatives variously substituted at C-2 position were synthesized and evaluated for in vitro antimycobacterial activity. Seventeen compounds exhibited potential activity (MIC ⩽6.25μg/mL) against Mycobacterium tuberculosis (H37Rv), in particular the compounds 3d and 3j having an MIC value of 0.39μg/mL. None of the compounds exhibited cytotoxicity when using an MTT assay in VERO cells. To further investigate the structure-activity relationship, CoMFA (q(2)=0.507, r(2)=0.923) and CoMSIA (q(2)=0.665, r(2)=0.977) models were performed on the basis of antimycobacterial activity data. The 3D-QSAR study of these compounds can provide useful information for further rational design of novel quinoxaline 1,4-di-N-oxides for treatment of tuberculosis.

  1. How to Deal with Low-Resolution Target Structures: Using SAR, Ensemble Docking, Hydropathic Analysis, and 3D-QSAR to Definitively Map the αβ-Tubulin Colchicine Site

    PubMed Central

    Da, Chenxiao; Mooberry, Susan L.; Gupton, John T.; Kellogg, Glen E.

    2013-01-01

    αβ-tubulin colchicine site inhibitors (CSIs) from four scaffolds that we previously tested for antiproliferative activity were modeled to better understand their effect on microtubules. Docking models, constructed by exploiting the SAR of a pyrrole subset and HINT scoring, guided ensemble docking of all 59 compounds. This conformation set and two variants having progressively less structure knowledge were subjected to CoMFA, CoMFA+HINT, and CoMSIA 3D-QSAR analyses. The CoMFA+HINT model (docked alignment) showed the best statistics: leave-one-out q2 of 0.616, r2 of 0.949 and r2pred (internal test set) of 0.755. An external (tested in other laboratories) collection of 24 CSIs from eight scaffolds were evaluated with the 3D-QSAR models, which correctly ranked their activity trends in 7/8 scaffolds for CoMFA+HINT (8/8 for CoMFA). The combination of SAR, ensemble docking, hydropathic analysis and 3D-QSAR provides an atomic-scale colchicine site model more consistent with a target structure resolution much higher than the ~3.6 Å available for αβ-tubulin. PMID:23961916

  2. 3D-QSAR study of benzotriazol-1-yl carboxamide scaffold as monoacylglycerol lipase inhibitors

    PubMed Central

    Afzal, Obaid; Kumar, Suresh; Kumar, Rajiv; Jaggi, Manu; Bawa, Sandhya

    2014-01-01

    Purpose: The purpose of this study is to build up the 3D pharmacophore of Monoacylglycerol lipase (MAGL) inhibitor and to provide the basis to design the novel and potent MAGL inhibitors. Material and Method: A 3D-QSAR study on benztriazol-1-yl carboxamide derivatives as monoacylglycerol lipase (MAGL) inhibitors was successfully performed by means of pharmacophore mapping using PHASE 3.5 module of Schrφdinger-9.4. Result: The 3D-QSAR obtained from APRRR-105 hypothesis was found to be statistically good with r2 = 0.9228 and q2 = 0.871, taking PLS factor 4. The statistical significance of the model was also confirmed by a high value of Fisher's ratio of 82.8 and a very low value of root-mean-square error (RMSE) 0.2564. Another parameter which signifies the model predictivity is Pearson R. Its value of 0.9512 showed that the correlation between predicted and observed activities for the test set compounds is excellent. Conclusion: The study suggested that one H-bond acceptor, one positive center, and proper positioning of hydrophobic groups near the distal aromatic ring C are the crucial determinants for MAGL inhibition. Thus, it can be assumed that the present QSAR analysis is enough to demonstrate MAGL inhibition with the help of APRRR-105 hypothesis and will be helpful in designing novel and potent MAGL inhibitors. PMID:25400409

  3. Study on the activity of non-purine xanthine oxidase inhibitor by 3D-QSAR modeling and molecular docking

    NASA Astrophysics Data System (ADS)

    Li, Peizhen; Tian, Yueli; Zhai, Honglin; Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun

    2013-11-01

    Non-purine derivatives have been shown to be promising novel drug candidates as xanthine oxidase inhibitors. Based on three-dimensional quantitative structure-activity relationship (3D-QSAR) methods including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), two 3D-QSAR models for a series of non-purine xanthine oxidase (XO) inhibitors were established, and their reliability was supported by statistical parameters. Combined 3D-QSAR modeling and the results of molecular docking between non-purine xanthine oxidase inhibitors and XO, the main factors that influenced activity of inhibitors were investigated, and the obtained results could explain known experimental facts. Furthermore, several new potential inhibitors with higher activity predicted were designed, which based on our analyses, and were supported by the simulation of molecular docking. This study provided some useful information for the development of non-purine xanthine oxidase inhibitors with novel structures.

  4. 3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors

    PubMed Central

    Xie, Huiding; Qiu, Kaixiong; Xie, Xiaoguang

    2014-01-01

    Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models. The reliable and predictive CoMFA and CoMSIA models were obtained with statistical results (CoMFA: q2 = 0.636, r2ncv = 0.988, r2pred = 0.658; CoMSIA: q2 = 0.843, r2ncv = 0.989, r2pred = 0.601). This 3D QSAR approach provides significant insights that can be used to develop novel and potent SAIs. In addition, Genetic algorithm with linear assignment of hypermolecular alignment of database (GALAHAD) was used to derive 3D pharmacophore models. The selected pharmacophore model contains two acceptor atoms and four hydrophobic centers, which was used as a 3D query for virtual screening against NCI2000 database. Six hit compounds were obtained and their biological activities were further predicted by the CoMFA and CoMSIA models, which are expected to design potent and novel SAIs. PMID:25405729

  5. Identification of novel histone deacetylase 1 inhibitors by combined pharmacophore modeling, 3D-QSAR analysis, in silico screening and Density Functional Theory (DFT) approaches

    NASA Astrophysics Data System (ADS)

    Choubey, Sanjay K.; Mariadasse, Richard; Rajendran, Santhosh; Jeyaraman, Jeyakanthan

    2016-12-01

    Overexpression of HDAC1, a member of Class I histone deacetylase is reported to be implicated in breast cancer. Epigenetic alteration in carcinogenesis has been the thrust of research for few decades. Increased deacetylation leads to accelerated cell proliferation, cell migration, angiogenesis and invasion. HDAC1 is pronounced as the potential drug target towards the treatment of breast cancer. In this study, the biochemical potential of 6-aminonicotinamide derivatives was rationalized. Five point pharmacophore model with one hydrogen-bond acceptor (A3), two hydrogen-bond donors (D5, D6), one ring (R12) and one hydrophobic group (H8) was developed using 6-aminonicotinamide derivatives. The pharmacophore hypothesis yielded a 3D-QSAR model with correlation-coefficient (r2 = 0.977, q2 = 0.801) and it was externally validated with (r2pred = 0.929, r2cv = 0.850 and r2m = 0.856) which reveals the statistical significance of the model having high predictive power. The model was then employed as 3D search query for virtual screening against compound libraries (Zinc, Maybridge, Enamine, Asinex, Toslab, LifeChem and Specs) in order to identify novel scaffolds which can be experimentally validated to design future drug molecule. Density Functional Theory (DFT) at B3LYP/6-31G* level was employed to explore the electronic features of the ligands involved in charge transfer reaction during receptor ligand interaction. Binding free energy (ΔGbind) calculation was done using MM/GBSA which defines the affinity of ligands towards the receptor.

  6. 3D QSAR investigations on locomotor activity of 5-cyano-N1,6-disubstituted 2-thiouracil derivatives.

    PubMed

    Kuchekar, B S; Pore, Y V

    2010-06-01

    Three dimensional quantitative structure activity relationship (3D QSAR) investigations were carried out on a series of 5-cyano-N1,6-disubstituted 2-thiouracil derivatives for their locomotor activity. The structures of all compounds were built on a workspace of VlifeMDS3.5 molecular modeling software and 3D QSAR models were generated by applying a partial least square (PLS) linear regression analysis coupled with a stepwise variable selection method. Both derived models were found to be statistically significant in terms of regression and internal and external predictive ability (r(2) = 0.9414 and 0.8511, q(2) = 0.8582 and 0.6222, pred_r(2) = 0.5142 and 0.7917). The QSAR models indicated that both electrostatic and steric interaction energies were contributing significantly to locomotor activity of thiouracil derivatives. PMID:22491179

  7. Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1.

    PubMed

    Fatima, Sabiha; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2012-08-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) operates in a DNA damage signaling network. Molecular docking and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on human PARP-1 inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into a training set and a test set randomly in four different ways, partial least square analysis was performed to obtain QSAR models using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Derived models showed good statistical reliability that is evident from their r², q²(loo) and r²(pred) values. To obtain a consensus for predictive ability from all the models, average regression coefficient r²(avg) was calculated. CoMFA and CoMSIA models showed a value of 0.930 and 0.936, respectively. Information obtained from the best 3D-QSAR model was applied for optimization of lead molecule and design of novel potential inhibitors.

  8. 3D-QSAR Study of 7,8-Dialkyl-1,3-diaminopyrrolo-[3,2-f] Quinazolines with Anticancer Activity as DHFR Inhibitors

    NASA Astrophysics Data System (ADS)

    Chen, Jin-can; Chen, Lan-mei; Liao, Si-yan; Qian, Li; Zheng, Kang-cheng

    2009-06-01

    A three-dimensional quantitative structure-activity relationship (3D-QSAR) study of a series of 7,8-dialkyl-1,3-diaminopyrrolo-[3,2-f] quinazolines with anticancer activity as dihydrofolate reductase (DHFR) inhibitors was carried out by using the comparative molecular field analysis (CoMFA), on the basis of our reported 2D-QSAR of these compounds. The established 3D-QSAR model has good quality of statistics and good prediction ability; the non cross-validation correlation coefficient and the cross-validation value of this model are 0.993 and 0.619, respectively, the F value is 193.4, and the standard deviation SD is 0.208. This model indicates that the steric field factor plays a much more important role than the electrostatic one, in satisfying agreement with the published 2D-QSAR model. However, the 3D-QSAR model offers visual images of the steric field and the electrostatic field. The 3D-QSAR study further suggests the following: to improve the activity, the substituent R' should be selected to be a group with an adaptive bulk like Et or i-Pr, and the substituent R should be selected to be a larger alkyl. In particular, based on our present 3D-QSAR as well as the published 2D-QSAR, the experimentally-proposed hydrophobic binding mechanism on the receptor-binding site of the DHFR can be further explained in theory. Therefore, the QSAR studies help to further understand the “hydrophobic binding" action mechanism of this kind of compounds, and to direct the molecular design of new drugs with higher activity.

  9. Identification of potential influenza virus endonuclease inhibitors through virtual screening based on the 3D-QSAR model.

    PubMed

    Kim, J; Lee, C; Chong, Y

    2009-01-01

    Influenza endonucleases have appeared as an attractive target of antiviral therapy for influenza infection. With the purpose of designing a novel antiviral agent with enhanced biological activities against influenza endonuclease, a three-dimensional quantitative structure-activity relationships (3D-QSAR) model was generated based on 34 influenza endonuclease inhibitors. The comparative molecular similarity index analysis (CoMSIA) with a steric, electrostatic and hydrophobic (SEH) model showed the best correlative and predictive capability (q(2) = 0.763, r(2) = 0.969 and F = 174.785), which provided a pharmacophore composed of the electronegative moiety as well as the bulky hydrophobic group. The CoMSIA model was used as a pharmacophore query in the UNITY search of the ChemDiv compound library to give virtual active compounds. The 3D-QSAR model was then used to predict the activity of the selected compounds, which identified three compounds as the most likely inhibitor candidates.

  10. A combined 3D-QSAR and docking studies for the In-silico prediction of HIV-protease inhibitors

    PubMed Central

    2013-01-01

    Background Tremendous research from last twenty years has been pursued to cure human life against HIV virus. A large number of HIV protease inhibitors are in clinical trials but still it is an interesting target for researchers due to the viral ability to get mutated. Mutated viral strains led the drug ineffective but still used to increase the life span of HIV patients. Results In the present work, 3D-QSAR and docking studies were performed on a series of Danuravir derivatives, the most potent HIV- protease inhibitor known so far. Combined study of 3D-QSAR was applied for Danuravir derivatives using ligand-based and receptor-based protocols and generated models were compared. The results were in good agreement with the experimental results. Additionally, docking analysis of most active 32 and least active 46 compounds into wild type and mutated protein structures further verified our results. The 3D-QSAR and docking results revealed that compound 32 bind efficiently to the wild and mutated protein whereas, sufficient interactions were lost in compound 46. Conclusion The combination of two computational techniques would helped to make a clear decision that compound 32 with well inhibitory activity bind more efficiently within the binding pocket even in case of mutant virus whereas compound 46 lost its interactions on mutation and marked as least active compound of the series. This is all due to the presence or absence of substituents on core structure, evaluated by 3D-QSAR studies. This set of information could be used to design highly potent drug candidates for both wild and mutated form of viruses. PMID:23683267

  11. Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists

    NASA Astrophysics Data System (ADS)

    Ji, Yongjun; Shu, Mao; Lin, Yong; Wang, Yuanqiang; Wang, Rui; Hu, Yong; Lin, Zhihua

    2013-08-01

    The beta chemokine receptor 5 (CCR5) is an attractive target for pharmaceutical industry in the HIV-1, inflammation and cancer therapeutic areas. In this study, we have developed quantitative structure activity relationship (QSAR) models for a series of 41 azacycles CCR5 antagonists using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and Topomer CoMFA methods. The cross-validated coefficient q2 values of 3D-QASR (CoMFA, CoMSIA, and Topomer CoMFA) methods were 0.630, 0.758, and 0.852, respectively, the non-cross-validated R2 values were 0.979, 0.978, and 0.990, respectively. Docking studies were also employed to determine the most probable binding mode. 3D contour maps and docking results suggested that bulky groups and electron-withdrawing groups on the core part would decrease antiviral activity. Furthermore, docking results indicated that H-bonds and π bonds were favorable for antiviral activities. Finally, a set of novel derivatives with predicted activities were designed.

  12. 3D-QSAR and molecular fragment replacement study on diaminopyrimidine and pyrrolotriazine ALK inhibitors

    NASA Astrophysics Data System (ADS)

    Ke, Zhipeng; Lu, Tao; Liu, Haichun; Yuan, Haoliang; Ran, Ting; Zhang, Yanmin; Yao, Sihui; Xiong, Xiao; Xu, Jinxing; Xu, Anyang; Chen, Yadong

    2014-06-01

    Over expression of anaplastic lymphoma kinase (ALK) has been found in many types of cancer, and ALK is a promising therapeutic target for the treatment of cancer. To obtain new potent inhibitors of ALK, we conducted lead optimization using 3D-QSAR modeling and molecular docking investigation of 2,4-diaminopyrimidines and 2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazine-based compounds. Three favorable 3D-QSAR models (CoMFA with q2, 0.555; r2, 0.939; CoMSIA with q2, 0.625; r2, 0.974; Topomer CoMFA with q2, 0.557; r2 0.756) have been developed to predict the biological activity of novel compounds. Topomer Search was utilized for virtual screening to obtain suitable fragments. The novel compounds generated by molecular fragment replacement (MFR) were evaluated by Topomer CoMFA prediction, Glide (docking) and further evaluated with CoMFA and CoMSIA prediction. 25 novel 2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazine derivatives as potential ALK inhibitors were finally obtained. In this paper, a combination of CoMFA, CoMSIA and Topomer CoMFA could obtain favorable 3D-QSAR models and suitable fragments for ALK inhibitors optimization. The work flow which comprised 3D-QSAR modeling, Topomer Search, MFR, molecular docking and evaluating criteria could be applied to de novo drug design and the resulted compounds initiate us to further optimize and design new potential ALK inhibitors.

  13. Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

    PubMed

    Fatima, Sabiha; Jatavath, Mohan Babu; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-10-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors. PMID:25046176

  14. Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

    PubMed

    Fatima, Sabiha; Jatavath, Mohan Babu; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-10-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors.

  15. Anilides and quinolones with nitrogen-bearing substituents from benzothiophene and thienothiophene series: synthesis, photochemical synthesis, cytostatic evaluation, 3D-derived QSAR analysis and DNA-binding properties.

    PubMed

    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Depauw, Sabine; Martin-Kleiner, Irena; David-Cordonnier, Marie-Hélène; Tomić, Sanja; Kralj, Marijeta; Karminski-Zamola, Grace

    2014-01-01

    A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b, 10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the reaction of photochemical dehydrohalogenation from corresponding anilides. Anilides and quinolones were tested for the antiproliferative activity. Fused quinolones bearing protonated aminium group, quaternary ammonium group, N-methylated and protonated aminium group, amino and protonated amino group (8a, 9b, 10-12) showed very prominent anticancer activity, whereby the hydrochloride salt of N',N'-dimethylaminopropyl-substituted quinolone (14) was the most active one, having the IC50 concentration at submicromolar range in accordance with previous QSAR predictions. On the other hand, flexible anilides were among the less active. Chemometric analysis of investigated compounds was performed. 3D-derived QSAR analysis identified solubility, metabolitic stability and the possibility of the compound to be ionized at pH 4-8 as molecular properties that are positively correlated with anticancer activity of investigated compounds, while molecular flexibility, polarizability and sum of hydrophobic surface areas were found to be negatively correlated. Anilides 2a-b, 4-7 and quinolones 3a-b, 8a-b, 9b and 10-14 were evaluated for DNA binding propensities and topoisomerases I/II inhibition as part of their mechanism of action. Among the anilides, only compound 7 presented some DNA binding propensity whereas the quinolones 8b, 9b and 10-14 intercalate in the DNA base pairs, compounds 8b, 9b and 14 being the most efficient ones. The strongest DNA intercalators, compounds 8b, 9b and 14, were clearly distinguished from the other compounds according to their molecular descriptors by the PCA and PLS analysis.

  16. 3D-QSAR and Docking Studies of Pyrido[2,3-d]pyrimidine Derivatives as Wee1 Inhibitors

    NASA Astrophysics Data System (ADS)

    Zeng, Guo-hua; Wu, Wen-juan; Zhang, Rong; Sun, Jun; Xie, Wen-guo; Shen, Yong

    2012-06-01

    In order to investigate the inhibiting mechanism and obtain some helpful information for designing functional inhibitors against Wee1, three-dimensional quantitative structure-activity relationship (3D-QSAR) and docking studies have been performed on 45 pyrido[2,3-d] pyrimidine derivatives acting as Wee1 inhibitors. Two optimal 3D-QSAR models with significant statistical quality and satisfactory predictive ability were established, including the CoMFA model (q2=0.707, R2=0.964) and CoMSIA model (q2=0.645, R2=0.972). The external validation indicated that both CoMFA and CoMSIA models were quite robust and had high predictive power with the predictive correlation coefficient values of 0.707 and 0.794, essential parameter rm2 values of 0.792 and 0.826, the leave-one-out r2m(LOO) values of 0.781 and 0.809, r2m(overall) values of 0.787 and 0.810, respectively. Moreover, the appropriate binding orientations and conformations of these compounds interacting with Wee1 were revealed by the docking studies. Based on the CoMFA and CoMSIA contour maps and docking analyses, several key structural requirements of these compounds responsible for inhibitory activity were identified as follows: simultaneously introducing high electropositive groups to the substituents R1 and R5 may increase the activity, the substituent R2 should be smaller bulky and higher electronegative, moderate-size and strong electron-withdrawing groups for the substituent R3 is advantageous to the activity, but the substituent X should be medium-size and hydrophilic. These theoretical results help to understand the action mechanism and design novel potential Wee1 inhibitors.

  17. 3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors

    NASA Astrophysics Data System (ADS)

    Ungwitayatorn, Jiraporn; Samee, Weerasak; Pimthon, Jutarat

    2004-02-01

    The three-dimensional quantitative structure-activity relationship (3D-QSAR) approach using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was applied to a series of 30 chromone derivatives, a new class of HIV-1 protease inhibitors. The best predictive CoMFA model gives cross-validated r2 ( q2)=0.763, non-cross-validated r2=0.967, standard error of estimate ( S)=5.092, F=90.701. The best CoMSIA model has q2=0.707, non-cross-validated r2=0.943, S=7.018, F=51.734, included steric, electrostatic, hydrophobic, and hydrogen bond donor fields. The predictive ability of these models was validated by a set of five compounds that were not included in the training set. The calculated (predicted) and experimental inhibitory activities were well correlated. The contour maps obtained from CoMFA and CoMSIA models were in agreement with the previous docking study for this chromone series.

  18. 3D QSAR studies of hydroxylated polychlorinated biphenyls as potential xenoestrogens.

    PubMed

    Ruiz, Patricia; Ingale, Kundan; Wheeler, John S; Mumtaz, Moiz

    2016-02-01

    Mono-hydroxylated polychlorinated biphenyls (OH-PCBs) are found in human biological samples and lack of data on their potential estrogenic activity has been a source of concern. We have extended our previous in silico 2D QSAR study through the application of advance techniques such as docking and 3D QSAR to gain insights into their estrogen receptor (ERα) binding. The results support our earlier findings that the hydroxyl group is the most important feature on the compounds; its position, orientation and surroundings in the structure are influential for the binding of OH-PCBs to ERα. This study has also revealed the following additional interactions that influence estrogenicity of these chemicals (a) the aromatic interactions of the biphenyl moieties with the receptor, (b) hydrogen bonding interactions of the p-hydroxyl group with key amino acids ARG394 and GLU353, (c) low or no electronegative substitution at para-positions of the p-hydroxyl group, (d) enhanced electrostatic interactions at the meta position on the B ring, and (e) co-planarity of the hydroxyl group on the A ring. In combination the 2D and 3D QSAR approaches have led us to the support conclusion that the hydroxyl group is the most important feature on the OH-PCB influencing the binding to estrogen receptors, and have enhanced our understanding of the mechanistic details of estrogenicity of this class of chemicals. Such in silico computational methods could serve as useful tools in risk assessment of chemicals. PMID:26598992

  19. More effective antimicrobial mastoparan derivatives, generated by 3D-QSAR-Almond and computational mutagenesis.

    PubMed

    Avram, Speranta; Buiu, Catalin; Borcan, Florin; Milac, Adina-Luminita

    2012-02-01

    Antimicrobial peptides are drugs used against a wide range of pathogens which present a great advantage: in contrast with antibiotics they do not develop resistance. The wide spectrum of antimicrobial peptides advertises them in the research and pharmaceutical industry as attractive starting points for obtaining new, more effective analogs. Here we predict the antimicrobial activity against Bacillus subtilis (expressed as minimal inhibitory concentration values) for 33 mastoparan analogs and their new derivatives by a non-aligned 3D-QSAR (quantitative structure-activity relationship) method. We establish the contribution to antimicrobial activity of molecular descriptors (hydrophobicity, hydrogen bond donor and steric), correlated with contributions from the membrane environment (sodium, potassium, chloride). Our best QSAR models show significant cross-validated correlation q(2) (0.55-0.75), fitted correlation r(2) (greater than 0.90) coefficients and standard error of prediction SDEP (less than 0.250). Moreover, based on our most accurate 3D-QSAR models, we propose nine new mastoparan analogs, obtained by computational mutagenesis, some of them predicted to have significantly improved antimicrobial activity compared to the parent compound.

  20. A Combined Pharmacophore Modeling, 3D QSAR and Virtual Screening Studies on Imidazopyridines as B-Raf Inhibitors

    PubMed Central

    Xie, Huiding; Chen, Lijun; Zhang, Jianqiang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-01-01

    B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). The best pharmacophore model obtained which was used in effective alignment of the data set contains two acceptor atoms, three donor atoms and three hydrophobes. In succession, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 39 imidazopyridine BRIs to build three dimensional quantitative structure-activity relationship (3D QSAR) models based on both pharmacophore and docking alignments. The CoMSIA model based on the pharmacophore alignment shows the best result (q2 = 0.621, r2pred = 0.885). This 3D QSAR approach provides significant insights that are useful for designing potent BRIs. In addition, the obtained best pharmacophore model was used for virtual screening against the NCI2000 database. The hit compounds were further filtered with molecular docking, and their biological activities were predicted using the CoMSIA model, and three potential BRIs with new skeletons were obtained. PMID:26035757

  1. Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular si...

  2. Compound profiling and 3D-QSAR studies of hydrazone derivatives with activity against intracellular Trypanosoma cruzi.

    PubMed

    Costa, Lívia Bandeira; Cardoso, Marcos Veríssimo de Oliveira; de Oliveira Filho, Gevanio Bezerra; de Moraes Gomes, Paulo André Teixeira; Espíndola, José Wanderlan Pontes; de Jesus Silva, Thays Gabrielle; Torres, Pedro Henrique Monteiro; Silva Junior, Floriano Paes; Martin, Julio; de Figueiredo, Regina Célia Bressan Queiroz; Leite, Ana Cristina Lima

    2016-04-15

    Chagas disease is a tropical disease caused by the parasite Trypanosoma cruzi, which is endemic in Central and South America. Few treatments are available with effectiveness limited to the early (acute) stage of disease, significant toxicity and widespread drug resistance. In this work we report the outcome of a HTS-ready assay chemical library screen to identify novel, nontoxic, small-molecule inhibitors of T. cruzi. We have selected 50 compounds that possess hydrazone as a common group. The compounds were screened using recombinant T. cruzi (Tulahuen strain) expressing beta-galactosidase. A 3D quantitative structure-activity relationship (QSAR) analysis was performed using descriptors calculated from comparative molecular field analysis (CoMFA). Our findings show that of the fifty selected hydrazones, compounds LpQM-19, 28 and 31 displayed the highest activity against T. cruzi, leading to a selectivity index (SI) of 20-fold. The 3D-QSAR analysis indicates that a particular electrostatic arrangement, where electron-deficient atoms are aligned along the molecule main axis positively correlates with compound biological activity. These results provide new candidate molecules for the development of treatments against Chagas disease. PMID:26964673

  3. Rigorous Treatment of Multi-species Multi-mode Ligand-Receptor Interactions in 3D-QSAR: CoMFA Analysis of Thyroxine Analogs Binding to Transthyretin

    PubMed Central

    Natesan, Senthil; Wang, Tiansheng; Lukacova, Viera; Bartus, Vladimir; Khandelwal, Akash; Balaz, Stefan

    2011-01-01

    For a rigorous analysis of the receptor-ligand binding, speciation of the ligands caused by ionization, tautomerism, covalent hydration, and dynamic stereoisomerism needs to be considered. Each species may bind in several orientations or conformations (modes), especially for flexible ligands and receptors. A thermodynamic description of the multi-species (MS), multi-mode (MM) binding events shows that the overall association constant is equal to the weighted sum of the sums of microscopic association constants of individual modes for each species, with the weights given by the unbound fractions of individual species. This expression is a prerequisite for a precise quantitative characterization of the ligand-receptor interactions in both structure-based and ligand-based structure-activity analyses. We have implemented the MS-MM correlation expression into the Comparative Molecular Field Analysis (CoMFA), which deduces a map of the binding site from structures and binding affinities of a ligand set, in the absence of experimental structural information on the receptor. The MS-MM CoMFA approach was applied to published data for binding to transthyretin of 28 thyroxine analogs, each forming up to four ionization species under physiological conditions. The published X-ray structures of several analogs, exhibiting multiple binding modes, served as templates for the MS-MM superposition of thyroxine analogs. Additional modes were generated for compounds with flexible alkyl substituents, to identify bound conformations. The results demonstrate that the MS-MM modification improved predictive abilities of the CoMFA models, even for the standard procedure with MS-MM selected species and modes. The predicted prevalences of individual modes and the generated receptor site model are in reasonable agreement with the available X-ray data. The calibrated model can help in the design of inhibitors of transthyretin amyloid fibril formation. PMID:21476521

  4. Combined 3D-QSAR and Molecular Docking Study for Identification of Diverse Natural Products as Potent Pf ENR Inhibitors.

    PubMed

    Wadhwa, Preeti; Saha, Debasmita; Sharma, Anuj

    2015-01-01

    An in-house library of 200 molecules from natural plant products was designed in order to evaluate their binding to Plasmodium ACP enoyl reductase (ENR), a promising biological target for antimalarial chemotherapeutics. The binding site of PfENR was explored computationally and the molecules were docked using AutoDock. Furthermore, the top-ranked scaffolds from docking studies were also compared with known PfENR inhibitors using 3D-QSAR. To this effect, a 3D-QSAR model was derived from a set of experimentally established PfENR inhibitors, using Comparative Molecular Force Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The best optimum CoMFA model exhibited a leave-one-out correlation coefficient (q2) and a noncross- validated correlation coefficient (r2) of 0.630 and 0.911, respectively. The result of this cumulative approach proposed five structurally distinct natural products as potent PfENR inhibitors. This study may lay a stepping stone towards Functional oriented synthesis (FOS) of novel PfENR inhibitors in future. PMID:26517356

  5. Amino substituted benzimidazo[1,2-a]quinolines: Antiproliferative potency, 3D QSAR study and DNA binding properties.

    PubMed

    Perin, Nataša; Nhili, Raja; Cindrić, Maja; Bertoša, Branimir; Vušak, Darko; Martin-Kleiner, Irena; Laine, William; Karminski-Zamola, Grace; Kralj, Marijeta; David-Cordonnier, Marie-Hélène; Hranjec, Marijana

    2016-10-21

    We describe the synthesis, 3D-derived quantitative structure-activity relationship (QSAR), antiproliferative activity and DNA binding properties of a series of 2-amino, 5-amino and 2,5-diamino substituted benzimidazo[1,2-a]quinolines prepared by environmentally friendly uncatalyzed microwave assisted amination. The antiproliferative activities were assessed in vitro against colon, lung and breast carcinoma cell lines; activities ranged from submicromolar to micromolar. The strongest antiproliferative activity was demonstrated by 2-amino-substituted analogues, whereas 5-amino and or 2,5-diamino substituted derivatives resulted in much less activity. Derivatives bearing 4-methyl- or 3,5-dimethyl-1-piperazinyl substituents emerged as the most active. DNA binding properties and the mode of interaction of chosen substituted benzimidazo[1,2-a]quinolines prepared herein were studied using melting temperature studies, a series of spectroscopic studies (UV/Visible, fluorescence, and circular dichroism), and biochemical experiments (topoisomerase I-mediated DNA relaxation and DNase I footprinting experiments). Both compound 36 and its bis-quaternary iodide salt 37 intercalate between adjacent base pairs of the DNA helix while compound 33 presented a very weak topoisomerase I poisoning activity. A 3D-QSAR analysis was performed to identify hydrogen bonding properties, hydrophobicity, molecular flexibility and distribution of hydrophobic regions as these molecular properties had the highest impact on the antiproliferative activity against the three cell lines. PMID:27448912

  6. Amino substituted benzimidazo[1,2-a]quinolines: Antiproliferative potency, 3D QSAR study and DNA binding properties.

    PubMed

    Perin, Nataša; Nhili, Raja; Cindrić, Maja; Bertoša, Branimir; Vušak, Darko; Martin-Kleiner, Irena; Laine, William; Karminski-Zamola, Grace; Kralj, Marijeta; David-Cordonnier, Marie-Hélène; Hranjec, Marijana

    2016-10-21

    We describe the synthesis, 3D-derived quantitative structure-activity relationship (QSAR), antiproliferative activity and DNA binding properties of a series of 2-amino, 5-amino and 2,5-diamino substituted benzimidazo[1,2-a]quinolines prepared by environmentally friendly uncatalyzed microwave assisted amination. The antiproliferative activities were assessed in vitro against colon, lung and breast carcinoma cell lines; activities ranged from submicromolar to micromolar. The strongest antiproliferative activity was demonstrated by 2-amino-substituted analogues, whereas 5-amino and or 2,5-diamino substituted derivatives resulted in much less activity. Derivatives bearing 4-methyl- or 3,5-dimethyl-1-piperazinyl substituents emerged as the most active. DNA binding properties and the mode of interaction of chosen substituted benzimidazo[1,2-a]quinolines prepared herein were studied using melting temperature studies, a series of spectroscopic studies (UV/Visible, fluorescence, and circular dichroism), and biochemical experiments (topoisomerase I-mediated DNA relaxation and DNase I footprinting experiments). Both compound 36 and its bis-quaternary iodide salt 37 intercalate between adjacent base pairs of the DNA helix while compound 33 presented a very weak topoisomerase I poisoning activity. A 3D-QSAR analysis was performed to identify hydrogen bonding properties, hydrophobicity, molecular flexibility and distribution of hydrophobic regions as these molecular properties had the highest impact on the antiproliferative activity against the three cell lines.

  7. Pharmacophore modeling and atom-based 3D-QSAR studies on amino derivatives of indole as potent isoprenylcysteine carboxyl methyltransferase (Icmt) inhibitors

    NASA Astrophysics Data System (ADS)

    Bhadoriya, Kamlendra Singh; Sharma, Mukesh C.; Jain, Shailesh V.

    2015-02-01

    Icmt enzymes are of particular importance in the post-translational modification of proteins that are involved in the regulation of cell growth. Thus, effective Icmt inhibitors may be of significant therapeutic importance in oncogenesis. To determine the structural requirements responsible for high affinity of previously reported amino derivatives of indole as Icmt inhibitors, a successful pharmacophore generation and atom-based 3D-QSAR analysis have been carried out. The best four-point pharmacophore model with four features HHRR: two hydrophobic groups (H) and two aromatic rings (R) as pharmacophore features was developed by PHASE module of Schrodinger suite. In this study, highly predictive 3D-QSAR models have been developed for Icmt inhibition using HHRR.191 hypothesis. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least-square (PLS) statistics results. The validation of the PHASE model was done by dividing the dataset into training and test set. The statistically significant the four-point pharmacophore hypothesis yielded a 3D-QSAR model with good PLS statistics results (R2 = 0.9387, Q2 = 0.8132, F = 114.8, SD = 0.1567, RMSE = 0.2682, Pearson-R = 0.9147). The generated model showed excellent predictive power, with a correlation coefficient of Q2 = 0.8132. The results of ligand-based pharmacophore hypothesis and atom-based 3D-QSAR provide detailed structural insights as well as highlights important binding features of novel amino derivatives of indole as Icmt inhibitors which can afford guidance for the rational drug design of novel, potent and promising Icmt inhibitors with enhanced potencies and may prove helpful for further lead optimization and virtual screening.

  8. 3D QSAR and molecular docking studies of benzimidazole derivatives as hepatitis C virus NS5B polymerase inhibitors.

    PubMed

    Patel, Pallav D; Patel, Maulik R; Kaushik-Basu, Neerja; Talele, Tanaji T

    2008-01-01

    The urgent need for novel HCV antiviral agents has provided an impetus for understanding the structural requisites of NS5B polymerase inhibitors at the molecular level. Toward this objective, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of 67 HCV NS5B polymerase inhibitors were performed using two methods. First, ligand-based 3D QSAR studies were performed based on the lowest energy conformations employing the atom fit alignment method. Second, receptor-based 3D QSAR models were derived from the predicted binding conformations obtained by docking all NS5B inhibitors at the allosteric binding site of NS5B (PDB ID: 2dxs). Results generated from the ligand-based model were found superior (r2cv values of 0.630 for CoMFA and 0.668 for CoMSIA) to those obtained by the receptor-based model (r2cv values of 0.536 and 0.561 for CoMFA and CoMSIA, respectively). The predictive ability of the models was validated using a structurally diversified test set of 22 compounds that had not been included in a preliminary training set of 45 compounds. The predictive r2 values for the ligand-based CoMFA and CoMSIA models were 0.734 and 0.800, respectively, while the corresponding predictive r2 values for the receptor-based CoMFA and CoMSIA models were 0.538 and 0.639, respectively. The greater potency of the tryptophan derivatives over that of the tyrosine derivatives was interpreted based on CoMFA steric and electrostatic contour maps. The CoMSIA results revealed that for a NS5B inhibitor to have appreciable inhibitory activity it requires hydrogen bond donor and acceptor groups at the 5-position of the indole ring and an R substituent at the chiral carbon, respectively. Interpretation of the CoMFA and CoMSIA contour maps in context of the topology of the allosteric binding site of NS5B provided insight into NS5B-inhibitor interactions. Taken together, the present 3D QSAR models were found to accurately predict the HCV NS5B

  9. Biological Evaluation and 3D-QSAR Studies of Curcumin Analogues as Aldehyde Dehydrogenase 1 Inhibitors

    PubMed Central

    Wang, Hui; Du, Zhiyun; Zhang, Changyuan; Tang, Zhikai; He, Yan; Zhang, Qiuyan; Zhao, Jun; Zheng, Xi

    2014-01-01

    Aldehyde dehydrogenase 1 (ALDH1) is reported as a biomarker for identifying some cancer stem cells, and down-regulation or inhibition of the enzyme can be effective in anti-drug resistance and a potent therapeutic for some tumours. In this paper, the inhibitory activity, mechanism mode, molecular docking and 3D-QSAR (three-dimensional quantitative structure activity relationship) of curcumin analogues (CAs) against ALDH1 were studied. Results demonstrated that curcumin and CAs possessed potent inhibitory activity against ALDH1, and the CAs compound with ortho di-hydroxyl groups showed the most potent inhibitory activity. This study indicates that CAs may represent a new class of ALDH1 inhibitor. PMID:24840575

  10. 3D-QSAR, molecular docking and molecular dynamics studies of a series of RORγt inhibitors.

    PubMed

    Wang, Fangfang; Yang, Wei; Shi, Yonghui; Le, Guowei

    2015-09-01

    The discovery of clinically relevant inhibitors of retinoic acid receptor-related orphan receptor-gamma-t (RORγt) for autoimmune diseases therapy has proven to be a challenging task. In the present work, to find out the structural features required for the inhibitory activity, we show for the first time a three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations for a series of novel thiazole/thiophene ketone amides with inhibitory activity at the RORγt receptor. The optimum CoMFA and CoMSIA models, derived from ligand-based superimposition I, exhibit leave-one-out cross-validated correlation coefficient (R(2)cv) of .859 and .805, respectively. Furthermore, the external predictive abilities of the models were evaluated by a test set, producing the predicted correlation coefficient (R(2)pred) of .7317 and .7097, respectively. In addition, molecular docking analysis was applied to explore the binding modes between the inhibitors and the receptor. MD simulation and MM/PBSA method were also employed to study the stability and rationality of the derived conformations, and the binding free energies in detail. The QSAR models and the results of molecular docking, MD simulation, binding free energies corroborate well with each other and further provide insights regarding the development of novel RORγt inhibitors with better activity.

  11. Multi-conformation 3D QSAR study of benzenesulfonyl-pyrazol-ester compounds and their analogs as cathepsin B inhibitors

    PubMed Central

    Zhou, Zhigang; Wang, Yanli; Bryant, Stephen H.

    2011-01-01

    Cathepsin B has been found being responsible for many human diseases. Inhibitors of cathepsin B, a ubiquitous lysosomal cysteine protease, have been developed as a promising treatment for human diseases resulting from malfunction and over-expression of this enzyme. Through a high throughput screening assay, a set of compounds were found able to inhibit the enzymatic activity of cathepsin B. The binding structures of these active compounds were modeled through docking simulation. Three-dimensional (3D) quantitative structure-activity relationship (QSAR) models were constructed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on the docked structures of the compounds. Strong correlations were obtained for both CoMFA and CoMSIA models with cross-validated correlation coefficients (q2) of 0.605 and 0.605 and the regression correlation coefficients (r2) of 0.999 and 0.997, respectively. The robustness of these models was further validated using leave-one-out (LOO) method and training-test set method. The activities of eight (8) randomly selected compounds were predicted using models built from training set of compounds with prediction errors of less than 1 unit for most compounds in CoMFA and CoMSIA models. Structural features for compounds with improved activity are suggested based on the analysis of the CoMFA and CoMSIA contour maps and the property map of the protein ligand binding site. These results may help to provide better understanding of the structure-activity relationship of cathepsin B inhibitors and to facilitate lead optimization and novel inhibitor design. The multi-conformation method to build 3D QSAR is very effective approach to obtain satisfactory models with high correlation with experimental results and high prediction power for unknown compounds. PMID:21798778

  12. 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide

    PubMed Central

    Li, Shun-Lai; He, Mao-Yu; Du, Hong-Guang

    2011-01-01

    The active metabolite of the novel immunosuppressive agent leflunomide has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite. The statistical results, cross-validated rCV2 (0.664) and non cross-validated r2 (0.687), show a good predictive ability. The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme. PMID:21686163

  13. Molecular docking and 3D-QSAR studies on triazolinone and pyridazinone, non-nucleoside inhibitor of HIV-1 reverse transcriptase.

    PubMed

    Sivan, Sree Kanth; Manga, Vijjulatha

    2010-06-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors of the HIV-1 reverse transcriptase. Recently a series of Triazolinone and Pyridazinone were reported as potent inhibitors of HIV-1 wild type reverse transcriptase. In the present study, docking and 3D quantitative structure activity relationship (3D QSAR) studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 31 molecules. Ligands were built and minimized using Tripos force field and applying Gasteiger-Hückel charges. These ligands were docked into protein active site using GLIDE 4.0. The docked poses were analyzed; the best docked poses were selected and aligned. CoMFA and CoMSIA fields were calculated using SYBYL6.9. The molecules were divided into training set and test set, a PLS analysis was performed and QSAR models were generated. The model showed good statistical reliability which is evident from the r2 nv, q2 loo and r2 pred values. The CoMFA model provides the most significant correlation of steric and electrostatic fields with biological activities. The CoMSIA model provides a correlation of steric, electrostatic, acceptor and hydrophobic fields with biological activities. The information rendered by 3D QSAR model initiated us to optimize the lead and design new potential inhibitors.

  14. Comparison of Different 2D and 3D-QSAR Methods on Activity Prediction of Histamine H3 Receptor Antagonists

    PubMed Central

    Dastmalchi, Siavoush; Hamzeh-Mivehroud, Maryam; Asadpour-Zeynali, Karim

    2012-01-01

    Histamine H3 receptor subtype has been the target of several recent drug development programs. Quantitative structure-activity relationship (QSAR) methods are used to predict the pharmaceutically relevant properties of drug candidates whenever it is applicable. The aim of this study was to compare the predictive powers of three different QSAR techniques, namely, multiple linear regression (MLR), artificial neural network (ANN), and HASL as a 3D QSAR method, in predicting the receptor binding affinities of arylbenzofuran histamine H3 receptor antagonists. Genetic algorithm coupled partial least square as well as stepwise multiple regression methods were used to select a number of calculated molecular descriptors to be used in MLR and ANN-based QSAR studies. Using the leave-group-out cross-validation technique, the performances of the MLR and ANN methods were evaluated. The calculated values for the mean absolute percentage error (MAPE), ranging from 2.9 to 3.6, and standard deviation of error of prediction (SDEP), ranging from 0.31 to 0.36, for both MLR and ANN methods were statistically comparable, indicating that both methods perform equally well in predicting the binding affinities of the studied compounds toward the H3 receptors. On the other hand, the results from 3D-QSAR studies using HASL method were not as good as those obtained by 2D methods. It can be concluded that simple traditional approaches such as MLR method can be as reliable as those of more advanced and sophisticated methods like ANN and 3D-QSAR analyses. PMID:25317190

  15. Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

    SciTech Connect

    Li, Xiaolin; Ye, Li; Wang, Xiaoxiang; Wang, Xinzhou; Liu, Hongling; Zhu, Yongliang; Yu, Hongxia

    2012-12-15

    Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 and non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.

  16. 3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors

    PubMed Central

    Fang, Yajing; Lu, Yulin; Zang, Xixi; Wu, Ting; Qi, XiaoJuan; Pan, Siyi; Xu, Xiaoyun

    2016-01-01

    Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti-Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids. The cross-validated coefficient (q2) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents. PMID:27049530

  17. 3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors.

    PubMed

    Fang, Yajing; Lu, Yulin; Zang, Xixi; Wu, Ting; Qi, XiaoJuan; Pan, Siyi; Xu, Xiaoyun

    2016-01-01

    Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti-Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids. The cross-validated coefficient (q(2)) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents. PMID:27049530

  18. A group center overlap based approach for "3D QSAR" studies on TIBO derivatives.

    PubMed

    Sapre, Nitin S; Gupta, Swagata; Pancholi, Nilanjana; Sapre, Neelima

    2009-04-30

    Current challenges in drug designing and lead optimization has reached a bottle neck where the main onus lies on rigorous validation to afford robust and predictive models. In the present study, we have suggested that predictive structure-activity relationship (SAR) models based on robust statistical analyses can serve as effective screening tools for large volume of compounds present either in chemical databases or in virtual libraries. 3D descriptors derived from the similarity-based alignment of molecules with respect to group center overlap from each individual template point and other "alignment averaged," but significant descriptors (ClogP, molar refractivity, connolly accessible area) were used to generate QSAR models. The results indicated that the artificial neural network method (r(2) = 0.902) proved to be superior to the multiple linear regression method (r(2) = 0.810). Cross validation of the models with an external set was reasonably satisfactory. Screening PubChem compound database based on the models obtained, yielded 14 newer modified compounds belonging to the TIBO class of inhibitors, as well as, two novel scaffolds, with enhanced binding efficacy as hits. These hits may be targeted toward potent lead-optimization and help in designing and synthesizing new compounds with potential therapeutic utility. PMID:18785154

  19. Docking and 3-D QSAR studies on the binding of tetrahydropyrimid-2-one HIV-1 protease inhibitors

    NASA Astrophysics Data System (ADS)

    Rao, Shashidhar N.; Balaji, Govardhan A.; Balaji, Vitukudi N.

    2013-06-01

    We present molecular docking and 3-D QSAR studies on a series of tetrahydropyrimid-2-one HIV-1 protease inhibitors whose binding affinities to the enzyme span nearly 6 orders of magnitude. The docking investigations have been carried out with Surflex (GEOM, GEOMX) and Glide (SP and XP) methodologies available through Tripos and Schrodinger suite of tools in the context of Sybyl-X and Maestro interfaces, respectively. The alignments for 3-D QSAR studies were obtained by using the automated Surflex-SIM methodology in Sybyl-X and the analyses were performed using the CoMFA and CoMSIA methods. Additionally, the top-ranked poses obtained from various docking protocols were also employed to generate CoMFA and CoMSIA models to evaluate the qualitative consistency of the docked models with experimental data. Our studies demonstrate that while there are a number of common features in the docked models obtained from Surflex-dock and Glide methodologies, the former sets of models are generally better correlated with deduced experimental binding modes based on the X-ray structures of known HIV-1 protease complexes with cyclic ureas. The urea moiety common to all the ligands are much more tightly aligned in Surflex docked structures than in the models obtained from Glide SP and XP dockings. The 3-D QSAR models are qualitatively and quantitatively similar to those previously reported, suggesting the utility of automatically generated alignments from Surflex-SIM methodology.

  20. A new computer program for QSAR-analysis: ARTE-QSAR.

    PubMed

    Van Damme, Sofie; Bultinck, Patrick

    2007-08-01

    A new computer program has been designed to build and analyze quantitative-structure activity relationship (QSAR) models through regression analysis. The user is provided with a range of regression and validation techniques. The emphasis of the program lies mainly in the validation of QSAR models in chemical applications. ARTE-QSAR produces an easy interpretable output from which the user can conclude if the obtained model is suitable for prediction and analysis. PMID:17394240

  1. A new computer program for QSAR-analysis: ARTE-QSAR.

    PubMed

    Van Damme, Sofie; Bultinck, Patrick

    2007-08-01

    A new computer program has been designed to build and analyze quantitative-structure activity relationship (QSAR) models through regression analysis. The user is provided with a range of regression and validation techniques. The emphasis of the program lies mainly in the validation of QSAR models in chemical applications. ARTE-QSAR produces an easy interpretable output from which the user can conclude if the obtained model is suitable for prediction and analysis.

  2. Molecular docking and 3D-QSAR studies on the glucocorticoid receptor antagonistic activity of hydroxylated polychlorinated biphenyls.

    PubMed

    Liu, S; Luo, Y; Fu, J; Zhou, J; Kyzas, G Z

    2016-01-01

    The glucocorticoid receptor (GR) antagonistic activities of hydroxylated polychlorinated biphenyls (HO-PCBs) were recently characterised. To further explore the interactions between HO-PCBs and the GR, and to elucidate structural characteristics that influence the GR antagonistic activity of HO-PCBs, molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed. Comparative molecular similarity indices analysis (CoMSIA) was performed using both ligand- and receptor-based alignment schemes. Results generated from the receptor-based model were found to be more satisfactory, with q(2) of 0.632 and r(2) of 0.931 compared with those from the ligand-based model. Some internal validation strategies (e.g. cross-validation analysis, bootstrapping analysis and Y-randomisation) and an external validation method were used respectively to further assess the stability and predictive ability of the derived model. Graphical interpretation of the model provided some insights into the structural features that affected the GR antagonistic activity of HO-PCBs. Molecular docking studies revealed that some key residues were critical for ligand-receptor interactions by forming hydrogen bonds (Glu540) and hydrophobic interactions with ligands (Ile539, Val543 and Trp577). Although CoMSIA sometimes depends on the alignment of the molecules, the information provided is beneficial for predicting the GR antagonistic activities of HO-PCB homologues and is helpful for understanding the binding mechanisms of HO-PCBs to GR. PMID:26848875

  3. Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach

    PubMed Central

    Naffaa, Moawiah M.; Bakht, Mohammed Afroz; Malhotra, Manav; Ganaie, Majid A.

    2014-01-01

    Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity. Furthermore, the essential features responsible for the activity were established by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their antiproliferation activity. Based on the pattern recognition studies obtained from QSAR results, ten novel compounds were designed and docked in the active domain of tubulin protein. One of the novel designed compounds “N1” exhibited binding energy −9.69 kcal/mol and predicted Ki 78.32 nM which was found to be better than colchicine. PMID:25383219

  4. 3D-QSAR modelling dataset of bioflavonoids for predicting the potential modulatory effect on P-glycoprotein activity.

    PubMed

    Wongrattanakamon, Pathomwat; Lee, Vannajan Sanghiran; Nimmanpipug, Piyarat; Jiranusornkul, Supat

    2016-12-01

    The data is obtained from exploring the modulatory activities of bioflavonoids on P-glycoprotein function by ligand-based approaches. Multivariate Linear-QSAR models for predicting the induced/inhibitory activities of the flavonoids were created. Molecular descriptors were initially used as independent variables and a dependent variable was expressed as pFAR. The variables were then used in MLR analysis by stepwise regression calculation to build the linear QSAR data. The entire dataset consisted of 23 bioflavonoids was used as a training set. Regarding the obtained MLR QSAR model, R of 0.963, R (2)=0.927, [Formula: see text], SEE=0.197, F=33.849 and q (2)=0.927 were achieved. The true predictabilities of QSAR model were justified by evaluation with the external dataset (Table 4). The pFARs of representative flavonoids were predicted by MLR QSAR modelling. The data showed that internal and external validations may generate the same conclusion. PMID:27626051

  5. 3D-QSAR modelling dataset of bioflavonoids for predicting the potential modulatory effect on P-glycoprotein activity.

    PubMed

    Wongrattanakamon, Pathomwat; Lee, Vannajan Sanghiran; Nimmanpipug, Piyarat; Jiranusornkul, Supat

    2016-12-01

    The data is obtained from exploring the modulatory activities of bioflavonoids on P-glycoprotein function by ligand-based approaches. Multivariate Linear-QSAR models for predicting the induced/inhibitory activities of the flavonoids were created. Molecular descriptors were initially used as independent variables and a dependent variable was expressed as pFAR. The variables were then used in MLR analysis by stepwise regression calculation to build the linear QSAR data. The entire dataset consisted of 23 bioflavonoids was used as a training set. Regarding the obtained MLR QSAR model, R of 0.963, R (2)=0.927, [Formula: see text], SEE=0.197, F=33.849 and q (2)=0.927 were achieved. The true predictabilities of QSAR model were justified by evaluation with the external dataset (Table 4). The pFARs of representative flavonoids were predicted by MLR QSAR modelling. The data showed that internal and external validations may generate the same conclusion.

  6. Docking-based three-dimensional quantitative structure-activity relationship (3D-QSAR) predicts binding affinities to aryl hydrocarbon receptor for polychlorinated dibenzodioxins, dibenzofurans, and biphenyls.

    PubMed

    Yuan, Jintao; Pu, Yuepu; Yin, Lihong

    2013-07-01

    Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) cause toxic effects after binding to an intracellular cytosolic receptor called the aryl hydrocarbon receptor (AhR). Thymic atrophy, weight loss, immunotoxicity, acute lethality, and induction of cytochrome P4501A1 have all been correlated with the binding affinity to AhR. To study the key molecular features for determining binding affinity to AhR, a homology model of AhR ligand-binding domains was developed, a molecular docking approach was employed to obtain docking-based conformations of all molecules in the whole set, and 3-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, namely, comparative molecular field analysis (CoMFA), was applied. A partial least square analysis was performed, and QSAR models were generated for a training set of 59 compounds. The generated QSAR model showed good internal and external statistical reliability, and in a comparison with other reported CoMFA models using different alignment methods, the docking-based CoMFA model showed some advantages.

  7. Searching for anthranilic acid-based thumb pocket 2 HCV NS5B polymerase inhibitors through a combination of molecular docking, 3D-QSAR and virtual screening.

    PubMed

    Vrontaki, Eleni; Melagraki, Georgia; Mavromoustakos, Thomas; Afantitis, Antreas

    2016-01-01

    A combination of the following computational methods: (i) molecular docking, (ii) 3-D Quantitative Structure Activity Relationship Comparative Molecular Field Analysis (3D-QSAR CoMFA), (iii) similarity search and (iv) virtual screening using PubChem database was applied to identify new anthranilic acid-based inhibitors of hepatitis C virus (HCV) replication. A number of known inhibitors were initially docked into the "Thumb Pocket 2" allosteric site of the crystal structure of the enzyme HCV RNA-dependent RNA polymerase (NS5B GT1b). Then, the CoMFA fields were generated through a receptor-based alignment of docking poses to build a validated and stable 3D-QSAR CoMFA model. The proposed model can be first utilized to get insight into the molecular features that promote bioactivity, and then within a virtual screening procedure, it can be used to estimate the activity of novel potential bioactive compounds prior to their synthesis and biological tests.

  8. In silico screening for identification of novel β-1,3-glucan synthase inhibitors using pharmacophore and 3D-QSAR methodologies.

    PubMed

    Meetei, Potshangbam Angamba; Rathore, R S; Prabhu, N Prakash; Vindal, Vaibhav

    2016-01-01

    The enzyme β-1,3-glucan synthase, which catalyzes the synthesis of β-1,3-glucan, an essential and unique structural component of the fungal cell wall, has been considered as a promising target for the development of less toxic anti-fungal agents. In this study, a robust pharmacophore model was developed and structure activity relationship analysis of 42 pyridazinone derivatives as β-1,3-glucan synthase inhibitors were carried out. A five-point pharmacophore model, consisting of two aromatic rings (R) and three hydrogen bond acceptors (A) was generated. Pharmacophore based 3D-QSAR model was developed for the same reported data sets. The generated 3D-QSAR model yielded a significant correlation coefficient value (R (2) = 0.954) along with good predictive power confirmed by the high value of cross-validated correlation coefficient (Q (2) = 0.827). Further, the pharmacophore model was employed as a 3D search query to screen small molecules database retrieved from ZINC to select new scaffolds. Finally, ADME studies revealed the pharmacokinetic efficiency of these compounds. PMID:27429875

  9. Constrained NBMPR Analogue Synthesis, Pharmacophore Mapping and 3D-QSAR Modeling of Equilibrative nucleoside Transporter 1 (ENT1) Inhibitory Activity

    PubMed Central

    Zhu, Zhengxiang; Buolamwini, John K.

    2009-01-01

    Conformationally constrained analogue synthesis was undertaken to aid in pharmacophore mapping and 3D QSAR analysis of nitrobenzylmercaptopurine riboside (NBMPR) congeners as equilibriative nucleoside transporter 1 (ENT1) inhibitors. In our previous study (Zhu et al., J. Med. Chem. 46, 831–837, 2003), novel regioisomeric nitro-1, 2, 3, 4-tetrahydroisoquinoline conformationally constrained analogues of NBMPR were synthesized and evaluated as ENT1 ligands. 7-NO2-1, 2, 3, 4-tetrahydroisoquino-2-yl purine riboside was identified as the analogue with the nitro group in the best orientation at the NBMPR binding site of ENT1. In the present study, further conformational constraining was introduced by synthesizing 5′-O, 8-cyclo derivatives. The flow cytometrically determined binding affinities indicated that the additional 5′-O, 8-cyclo constraining was unfavorable for binding to the ENT1 transporter. The structure-activity relationship (SAR) acquired was applied to pharmacophore mapping using the PHASE program. The best pharmacophore hypothesis obtained embodied an anti-conformation with three H-bond acceptors, one hydrophobic center, and two aromatic rings involving the 3′-OH, 4′-oxygen, the NO2 group, the benzyl phenyl and the imidazole and pyrimidine portions of the purine ring, respectively. A PHASE 3D-QSAR model derived with this pharmacophore yielded an r2 of 0.916 for four (4) PLS components, and an excellent external test set predictive r2 of 0.78 for 39 compounds. This pharmacophore was used for molecular alignment in a comparative molecular field analysis (CoMFA) 3D-QSAR study that also afforded a predictive model with external test set validation predictive r2 of 0.73. Thus, although limited, this study suggests that the bioactive conformation for NBMPR at the ENT1 transporter could be anti. The study has also suggested an ENT1 inhibitory pharmacophore, and established a predictive CoMFA 3D-QSAR model that might be useful for novel ENT1 inhibitor

  10. Investigation of Antigen-Antibody Interactions of Sulfonamides with a Monoclonal Antibody in a Fluorescence Polarization Immunoassay Using 3D-QSAR Models

    PubMed Central

    Wang, Zhanhui; Kai, Zhenpeng; Beier, Ross C.; Shen, Jianzhong; Yang, Xinling

    2012-01-01

    A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The affinities of the MAbSMR, expressed as Log10IC50, for 17 sulfonamide analogs were determined by competitive fluorescence polarization immunoassay (FPIA). The results demonstrated that the proposed pharmacophore model containing two hydrogen-bond acceptors, two hydrogen-bond donors and two hydrophobic centers characterized the structural features of the sulfonamides necessary for MAbSMR binding. Removal of two outliers from the initial set of 17 sulfonamide analogs improved the predictability of the models. The 3D-QSAR models of 15 sulfonamides based on CoMFA and CoMSIA resulted in q2 cv values of 0.600 and 0.523, and r2 values of 0.995 and 0.994, respectively, which indicates that both methods have significant predictive capability. Connolly surface analysis, which mainly focused on steric force fields, was performed to complement the results from CoMFA and CoMSIA. This novel study combining FPIA with pharmacophore modeling demonstrates that multidisciplinary research is useful for investigating antigen-antibody interactions and also may provide information required for the design of new haptens. PMID:22754368

  11. 3D-QSAR studies and shape based virtual screening for identification of novel hits to inhibit MbtA in Mycobacterium tuberculosis.

    PubMed

    Maganti, Lakshmi; Ghoshal, Nanda

    2015-01-01

    Mycobacterium tuberculosis, the pathogen responsible for tuberculosis, uses various strategies to survive in a variety of host lesions. The re-emergence of multi-drug-resistant strains of M. tuberculosis underlines the necessity to discover new molecules. Inhibitors of aryl acid adenylating enzyme, MbtA, involved in siderophore biosynthesis in M. tuberculosis, are being explored as potential anti tubercular agents. In this study, we have used 3D-QSAR models and shape based virtual screening to identify novel MbtA inhibitors. 3D-QSAR studies were carried out on nucleoside bisubstrate derivatives. Both Comparative Molecular Field Analysis (r(2) = .944 and r(2)(pred) = .938) and Comparative Molecular Similarity Indices Analysis (r(2) = .892 and r(2)(pred) = .842) models, developed using Gasteiger charges with all fields, predicted efficiently. A total of 13 hits were identified as novel prospective inhibitors for MbtA by utilizing an insilico workflow. Out of 13 hits, five top ranked hits were used for further molecular dynamics studies to gain more insights about the stability of the complexes. PMID:24417439

  12. Molecular docking, molecular dynamics simulation, and structure-based 3D-QSAR studies on the aryl hydrocarbon receptor agonistic activity of hydroxylated polychlorinated biphenyls.

    PubMed

    Cao, Fu; Li, Xiaolin; Ye, Li; Xie, Yuwei; Wang, Xiaoxiang; Shi, Wei; Qian, Xiangping; Zhu, Yongliang; Yu, Hongxia

    2013-09-01

    The binding interactions between hydroxylated polychlorinated biphenyls (HO-PCBs) and the aryl hydrocarbon receptor (AhR) are suspected of causing toxic effects. To understand the binding mode between HO-PCBs and AhR, and to explore the structural characteristics that influence the AhR agonistic activities of HO-PCBs, the combination of molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR), and molecular dynamics (MD) simulations was performed. Using molecular docking, the HO-PCBs were docked into the binding pocket of AhR, which was generated by homology modeling. Comparative molecular similarity index analysis (CoMSIA) models were subsequently developed from three different alignment rules. The optimum 3D-QSAR model showed good predictive ability (q(2)=0.583, R(2)=0.913) and good mechanism interpretability. The statistical reliability of the CoMSIA model was also validated. In addition, molecular docking and MD simulations were applied to explore the binding modes between the ligands and AhR. The results obtained from this study may lead to a better understanding of the interaction mechanism between HO-PCBs and AhR.

  13. Novel chemical scaffolds of the tumor marker AKR1B10 inhibitors discovered by 3D QSAR pharmacophore modeling

    PubMed Central

    Kumar, Raj; Son, Minky; Bavi, Rohit; Lee, Yuno; Park, Chanin; Arulalapperumal, Venkatesh; Cao, Guang Ping; Kim, Hyong-ha; Suh, Jung-keun; Kim, Yong-seong; Kwon, Yong Jung; Lee, Keun Woo

    2015-01-01

    Aim: Recent evidence suggests that aldo-keto reductase family 1 B10 (AKR1B10) may be a potential diagnostic or prognostic marker of human tumors, and that AKR1B10 inhibitors offer a promising choice for treatment of many types of human cancers. The aim of this study was to identify novel chemical scaffolds of AKR1B10 inhibitors using in silico approaches. Methods: The 3D QSAR pharmacophore models were generated using HypoGen. A validated pharmacophore model was selected for virtual screening of 4 chemical databases. The best mapped compounds were assessed for their drug-like properties. The binding orientations of the resulting compounds were predicted by molecular docking. Density functional theory calculations were carried out using B3LYP. The stability of the protein-ligand complexes and the final binding modes of the hit compounds were analyzed using 10 ns molecular dynamics (MD) simulations. Results: The best pharmacophore model (Hypo 1) showed the highest correlation coefficient (0.979), lowest total cost (102.89) and least RMSD value (0.59). Hypo 1 consisted of one hydrogen-bond acceptor, one hydrogen-bond donor, one ring aromatic and one hydrophobic feature. This model was validated by Fischer's randomization and 40 test set compounds. Virtual screening of chemical databases and the docking studies resulted in 30 representative compounds. Frontier orbital analysis confirmed that only 3 compounds had sufficiently low energy band gaps. MD simulations revealed the binding modes of the 3 hit compounds: all of them showed a large number of hydrogen bonds and hydrophobic interactions with the active site and specificity pocket residues of AKR1B10. Conclusion: Three compounds with new structural scaffolds have been identified, which have stronger binding affinities for AKR1B10 than known inhibitors. PMID:26051108

  14. Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking.

    PubMed

    Sun, Guohui; Fan, Tengjiao; Zhang, Na; Ren, Ting; Zhao, Lijiao; Zhong, Rugang

    2016-01-01

    DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O⁶ position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have been synthesized over the past decades to improve the chemotherapeutic effects of O⁶-alkylating agents. In the present study, we performed a three-dimensional quantitative structure activity relationship (3D-QSAR) study on 97 guanine derivatives as MGMT inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Three different alignment methods (ligand-based, DFT optimization-based and docking-based alignment) were employed to develop reliable 3D-QSAR models. Statistical parameters derived from the models using the above three alignment methods showed that the ligand-based CoMFA (Qcv² = 0.672 and Rncv² = 0.997) and CoMSIA (Qcv² = 0.703 and Rncv² = 0.946) models were better than the other two alignment methods-based CoMFA and CoMSIA models. The two ligand-based models were further confirmed by an external test-set validation and a Y-randomization examination. The ligand-based CoMFA model (Qext² = 0.691, Rpred² = 0.738 and slope k = 0.91) was observed with acceptable external test-set validation values rather than the CoMSIA model (Qext² = 0.307, Rpred² = 0.4 and slope k = 0.719). Docking studies were carried out to predict the binding modes of the inhibitors with MGMT. The results indicated that the obtained binding interactions were consistent with the 3D contour maps. Overall, the combined results of the 3D-QSAR and the docking obtained in this study provide an insight into the understanding of the interactions between guanine derivatives and MGMT protein, which will assist in designing novel MGMT inhibitors with desired activity. PMID:27347909

  15. Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking.

    PubMed

    Sun, Guohui; Fan, Tengjiao; Zhang, Na; Ren, Ting; Zhao, Lijiao; Zhong, Rugang

    2016-06-23

    DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O⁶ position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have been synthesized over the past decades to improve the chemotherapeutic effects of O⁶-alkylating agents. In the present study, we performed a three-dimensional quantitative structure activity relationship (3D-QSAR) study on 97 guanine derivatives as MGMT inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Three different alignment methods (ligand-based, DFT optimization-based and docking-based alignment) were employed to develop reliable 3D-QSAR models. Statistical parameters derived from the models using the above three alignment methods showed that the ligand-based CoMFA (Qcv² = 0.672 and Rncv² = 0.997) and CoMSIA (Qcv² = 0.703 and Rncv² = 0.946) models were better than the other two alignment methods-based CoMFA and CoMSIA models. The two ligand-based models were further confirmed by an external test-set validation and a Y-randomization examination. The ligand-based CoMFA model (Qext² = 0.691, Rpred² = 0.738 and slope k = 0.91) was observed with acceptable external test-set validation values rather than the CoMSIA model (Qext² = 0.307, Rpred² = 0.4 and slope k = 0.719). Docking studies were carried out to predict the binding modes of the inhibitors with MGMT. The results indicated that the obtained binding interactions were consistent with the 3D contour maps. Overall, the combined results of the 3D-QSAR and the docking obtained in this study provide an insight into the understanding of the interactions between guanine derivatives and MGMT protein, which will assist in designing novel MGMT inhibitors with desired activity.

  16. QSAR study and conformational analysis of 4-arylthiazolylhydrazones derived from 1-indanones with anti-Trypanosoma cruzi activity.

    PubMed

    Noguera, Guido J; Fabian, Lucas E; Lombardo, Elisa; Finkielsztein, Liliana

    2015-10-12

    A set of 4-arylthiazolylhydrazones derived from 1-indanones (TZHs) previously synthesized and assayed against Trypanosoma cruzi, the causative agent of Chagas disease, were explored in terms of conformational analysis. We found that TZHs can adopt four minimum energy conformations: cis (A, B and C) and trans. The possible bioactive conformation was selected by a 3D-QSAR model. Different molecular parameters were calculated to produce QSAR second-generation models. These QSAR results are discussed in conjunction with conformational analysis from molecular modeling studies. The main factor to determine the activity of the compounds was the partial charge at the N(3) atom (qN3). The predictive ability of the QSAR equations proposed was experimentally validated. The QSAR models developed in this study will be helpful to design novel potent TZHs.

  17. Structure-based and multiple potential three-dimensional quantitative structure-activity relationship (SB-MP-3D-QSAR) for inhibitor design.

    PubMed

    Du, Qi-Shi; Gao, Jing; Wei, Yu-Tuo; Du, Li-Qin; Wang, Shu-Qing; Huang, Ri-Bo

    2012-04-23

    The inhibitions of enzymes (proteins) are determined by the binding interactions between ligands and targeting proteins. However, traditional QSAR (quantitative structure-activity relationship) is a one-side technique, only considering the structures and physicochemical properties of inhibitors. In this study, the structure-based and multiple potential three-dimensional quantitative structure-activity relationship (SB-MP-3D-QSAR) is presented, in which the structural information of host protein is involved in the QSAR calculations. The SB-MP-3D-QSAR actually is a combinational method of docking approach and QSAR technique. Multiple docking calculations are performed first between the host protein and ligand molecules in a training set. In the targeting protein, the functional residues are selected, which make the major contribution to the binding free energy. The binding free energy between ligand and targeting protein is the summation of multiple potential energies, including van der Waals energy, electrostatic energy, hydrophobic energy, and hydrogen-bond energy, and may include nonthermodynamic factors. In the foundational QSAR equation, two sets of weighting coefficients {aj} and {bp} are assigned to the potential energy terms and to the functional residues, respectively. The two coefficient sets are solved by using iterative double least-squares (IDLS) technique in the training set. Then, the two sets of weighting coefficients are used to predict the bioactivities of inquired ligands. In an application example, the new developed method obtained much better results than that of docking calculations.

  18. Pharmacophore modeling, virtual screening and 3D-QSAR studies of 5-tetrahydroquinolinylidine aminoguanidine derivatives as sodium hydrogen exchanger inhibitors.

    PubMed

    Bhatt, Hardik G; Patel, Paresh K

    2012-06-01

    Sodium hydrogen exchanger (SHE) inhibitor is one of the most important targets in treatment of myocardial ischemia. In the course of our research into new types of non-acylguanidine, SHE inhibitory activities of 5-tetrahydroquinolinylidine aminoguanidine derivatives were used to build pharmacophore and 3D-QSAR models. Genetic Algorithm Similarity Program (GASP) was used to derive a 3D pharmacophore model which was used in effective alignment of data set. Eight molecules were selected on the basis of structure diversity to build 10 different pharmacophore models. Model 1 was considered as the best model as it has highest fitness score compared to other nine models. The obtained model contained two acceptor sites, two donor atoms and one hydrophobic region. Pharmacophore modeling was followed by substructure searching and virtual screening. The best CoMFA model, representing steric and electrostatic fields, obtained for 30 training set molecules was statistically significant with cross-validated coefficient (q(2)) of 0.673 and conventional coefficient (r(2)) of 0.988. In addition to steric and electrostatic fields observed in CoMFA, CoMSIA also represents hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. CoMSIA model was also significant with cross-validated coefficient (q(2)) and conventional coefficient (r(2)) of 0.636 and 0.986, respectively. Both models were validated by an external test set of eight compounds and gave satisfactory prediction (r(pred)(2)) of 0.772 and 0.701 for CoMFA and CoMSIA models, respectively. This pharmacophore based 3D-QSAR approach provides significant insights that can be used to design novel, potent and selective SHE inhibitors. PMID:22546667

  19. 3D-QSAR study and design of 4-hydroxyamino α-pyranone carboxamide analogues as potential anti-HCV agents

    NASA Astrophysics Data System (ADS)

    Li, Wenlian; Xiao, Faqi; Zhou, Mingming; Jiang, Xuejin; Liu, Jun; Si, Hongzong; Xie, Meng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-09-01

    The three dimensional-quantitative structure activity relationship (3D-QSAR) study was performed on a series of 4-hydroxyamino α-pyranone carboxamide analogues using comparative molecular similarity indices analysis (COMSIA). The purpose of the present study was to develop a satisfactory model providing a reliable prediction based on 4-hydroxyamino α-pyranone carboxamide analogues as anti-HCV (hepatitis C virus) inhibitors. The statistical results and the results of validation of this optimum COMSIA model were satisfactory. Furthermore, analysis of the contour maps helped to provide guidelines for finding structural requirement. Therefore, the satisfactory results from this study may provide useful guidelines for drug development of anti-HCV inhibitors.

  20. Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models

    PubMed Central

    Li, Yi-Fang; Chang, Yi-Qun; Deng, Jie; Li, Wei-Xi; Jian, Jie; Gao, Jia-Suo; Wan, Xin; Gao, Hao; Kurihara, Hiroshi; Sun, Ping-Hua; He, Rong-Rong

    2016-01-01

    The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2′R,3′R)-desgalloyloolongtheanin-3,3′-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 μg/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents. PMID:27694956

  1. 3D-QSAR-aided design, synthesis, in vitro and in vivo evaluation of dipeptidyl boronic acid proteasome inhibitors and mechanism studies.

    PubMed

    Lei, Meng; Feng, Huayun; Wang, Cheng; Li, Hailing; Shi, Jingmiao; Wang, Jia; Liu, Zhaogang; Chen, Shanshan; Hu, Shihe; Zhu, Yongqiang

    2016-06-01

    Proteasome had been clinically validated as an effective target for the treatment of cancers. Up to now, many structurally diverse proteasome inhibitors were discovered. And two of them were launched to treat multiple myeloma (MM) and mantle cell lymphoma (MCL). Based on our previous biological results of dipeptidyl boronic acid proteasome inhibitors, robust 3D-QSAR models were developed and structure-activity relationship (SAR) was summarized. Several structurally novel compounds were designed based on the theoretical models and finally synthesized. Biological results showed that compound 12e was as active as the standard bortezomib in enzymatic and cellular activities. In vivo pharmacokinetic profiles suggested compound 12e showed a long half-life, which indicated that it could be administered intravenously. Cell cycle analysis indicated that compound 12e inhibited cell cycle progression at the G2M stage. PMID:27117691

  2. A Structure-Activity Relationship Study of Imidazole-5-Carboxylic Acid Derivatives as Angiotensin II Receptor Antagonists Combining 2D and 3D QSAR Methods.

    PubMed

    Sharma, Mukesh C

    2016-03-01

    Two-dimensional (2D) and three-dimensional (3D) quantitative structure-activity relationship (QSAR) studies were performed for correlating the chemical composition of imidazole-5-carboxylic acid analogs and their angiotensin II [Formula: see text] receptor antagonist activity using partial least squares and k-nearest neighbor, respectively. For comparing the three different feature selection methods of 2D-QSAR, k-nearest neighbor models were used in conjunction with simulated annealing (SA), genetic algorithm and stepwise coupled with partial least square (PLS) showed variation in biological activity. The statistically significant best 2D-QSAR model having good predictive ability with statistical values of [Formula: see text] and [Formula: see text] was developed by SA-partial least square with the descriptors like [Formula: see text]count, 5Chain count, SdsCHE-index, and H-acceptor count, showing that increase in the values of these descriptors is beneficial to the activity. The 3D-QSAR studies were performed using the SA-PLS. A leave-one-out cross-validated correlation coefficient [Formula: see text] and predicate activity [Formula: see text] = 0.7226 were obtained. The information rendered by QSAR models may lead to a better understanding of structural requirements of substituted imidazole-5-carboxylic acid derivatives and also aid in designing novel potent antihypertensive molecules.

  3. 3D-QSAR and docking studies on 1-hydroxypyridin-2-one compounds as mutant isocitrate dehydrogenase 1 inhibitors

    NASA Astrophysics Data System (ADS)

    Wang, Zhenya; Chang, Yiqun; Han, Yushui; Liu, Kangjia; Hou, Jinsong; Dai, Chengli; Zhai, Yuanhao; Guo, Jialiang; Sun, Pinghua; Lin, Jing; Chen, Weimin

    2016-11-01

    Mutation of isocitrate dehydrogenase 1 (IDH1) which is frequently found in certain cancers such as glioma, sarcoma and acute myeloid leukemia, has been proven to be a potent drug target for cancer therapy. In silico methodologies such as 3D-QSAR and molecular docking were performed to explore compounds with better mutant isocitrate dehydrogenase 1 (MIDH1) inhibitory activity using a series of 40 newly reported 1-hydroxypyridin-2-one compounds as MIDH1 inhibitors. The satisfactory CoMFA and CoMSIA models obtained after internal and external cross-validation gave q2 values of 0.691 and 0.535, r2 values of 0.984 and 0.936, respectively. 3D contour maps generated from CoMFA and CoMSIA along with the docking results provided information about the structural requirements for better MIDH1 inhibitory activity. Based on the structure-activity relationship, 17 new potent molecules with better predicted activity than the most active compound in the literature have been designed.

  4. In silico exploration of c-KIT inhibitors by pharmaco-informatics methodology: pharmacophore modeling, 3D QSAR, docking studies, and virtual screening.

    PubMed

    Chaudhari, Prashant; Bari, Sanjay

    2016-02-01

    c-KIT is a component of the platelet-derived growth factor receptor family, classified as type-III receptor tyrosine kinase. c-KIT has been reported to be involved in, small cell lung cancer, other malignant human cancers, and inflammatory and autoimmune diseases associated with mast cells. Available c-KIT inhibitors suffer from tribulations of growing resistance or cardiac toxicity. A combined in silico pharmacophore and structure-based virtual screening was performed to identify novel potential c-KIT inhibitors. In the present study, five molecules from the ZINC database were retrieved as new potential c-KIT inhibitors, using Schrödinger's Maestro 9.0 molecular modeling suite. An atom-featured 3D QSAR model was built using previously reported c-KIT inhibitors containing the indolin-2-one scaffold. The developed 3D QSAR model ADHRR.24 was found to be significant (R2 = 0.9378, Q2 = 0.7832) and instituted to be sufficiently robust with good predictive accuracy, as confirmed through external validation approaches, Y-randomization and GH approach [GH score 0.84 and Enrichment factor (E) 4.964]. The present QSAR model was further validated for the OECD principle 3, in that the applicability domain was calculated using a "standardization approach." Molecular docking of the QSAR dataset molecules and final ZINC hits were performed on the c-KIT receptor (PDB ID: 3G0E). Docking interactions were in agreement with the developed 3D QSAR model. Model ADHRR.24 was explored for ligand-based virtual screening followed by in silico ADME prediction studies. Five molecules from the ZINC database were obtained as potential c-KIT inhibitors with high in -silico predicted activity and strong key binding interactions with the c-KIT receptor.

  5. Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents.

    PubMed

    Abdel-Atty, Mona M; Farag, Nahla A; Kassab, Shaymaa E; Serya, Rabah A T; Abouzid, Khaled A M

    2014-12-01

    In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl)acrylic acids IIIa-g (E), 4-(4-(substituted)phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted)phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted)phenyl) carbamoyl]benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50 ranging from 2.27 to 10.71μM. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties.

  6. Exploration of Novel Inhibitors for Bruton’s Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation

    PubMed Central

    Choi, Light; Woo Lee, Keun

    2016-01-01

    Bruton’s tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in many cellular signaling pathways. B cell malignancies are dependent on BCR signaling, thus making BTK an efficient therapeutic target. Over the last few years, significant efforts have been made in order to develop BTK inhibitors to treat B-cell malignancies, and autoimmunity or allergy/hypersensitivity but limited success has been achieved. Here in this study, 3D QSAR pharmacophore models were generated for Btk based on known IC50 values and experimental energy scores with extensive validations. The five features pharmacophore model, Hypo1, includes one hydrogen bond acceptor lipid, one hydrogen bond donor, and three hydrophobic features, which has the highest correlation coefficient (0.98), cost difference (112.87), and low RMS (1.68). It was further validated by the Fisher’s randomization method and test set. The well validated Hypo1 was used as a 3D query to search novel Btk inhibitors with different chemical scaffold using high throughput virtual screening technique. The screened compounds were further sorted by applying ADMET properties, Lipinski’s rule of five and molecular docking studies to refine the retrieved hits. Furthermore, molecular dynamic simulation was employed to study the stability of docked conformation and to investigate the binding interactions in detail. Several important hydrogen bonds with Btk were revealed, which includes the gatekeeper residues Glu475 and Met 477 at the hinge region. Overall, this study suggests that the proposed hits may be more effective inhibitors for cancer and autoimmune therapy. PMID:26784025

  7. Active site characterization and structure based 3D-QSAR studies on non-redox type 5-lipoxygenase inhibitors.

    PubMed

    Ul-Haq, Zaheer; Khan, Naveed; Zafar, Syed Kashif; Moin, Syed Tarique

    2016-06-10

    Structure-based 3D-QSAR study was performed on a class of 5-benzylidene-2-phenylthiazolinones non-redox type 5-LOX inhibitors. In this study, binding pocket of 5-Lipoxygenase (pdb id 3o8y) was identified by manual docking using 15-LOX (pdb id 2p0m) as a reference structure. Additionally, most of the binding site residues were found conserved in both structures. These non-redox inhibitors were then docked into the binding site of 5-LOX. To generate reliable CoMFA and CoMSIA models, atom fit data base alignment method using docked conformation of the most active compound was employed. The q(2)cv and r(2)ncv values for CoMFA model were found to be 0.549 and 0.702, respectively. The q(2)cv and r(2)ncv values for the selected CoMSIA model comprised four descriptors steric, electrostatic, hydrophobic and hydrogen bond donor fields were found to be 0.535 and 0.951, respectively. Obtained results showed that our generated model was statistically reliable. Furthermore, an external test set validates the reliability of the predicted model by calculating r(2)pred i.e.0.787 and 0.571 for CoMFA and CoMSIA model, respectively. 3D contour maps generated from CoMFA and CoMSIA models were utilized to determine the key structural features of ligands responsible for biological activities. The applied protocol will be helpful to design more potent and selective inhibitors of 5-LOX. PMID:27044904

  8. Benzimidazole derivatives. 3. 3D-QSAR/CoMFA model and computational simulation for the recognition of 5-HT(4) receptor antagonists.

    PubMed

    López-Rodríguez, María L; Murcia, Marta; Benhamú, Bellinda; Viso, Alma; Campillo, Mercedes; Pardo, Leonardo

    2002-10-24

    A three-dimensional quantitative structure-affinity relationship study (3D-QSAR), using the comparative molecular field analysis (CoMFA) method, and subsequent computational simulation of ligand recognition have been successfully applied to explain the binding affinities for the 5-HT(4) receptor (5-HT(4)R) of a series of benzimidazole-4-carboxamides and carboxylates derivatives 1-24. The K(i) values of these compounds are in the range from 0.11 to 10 000 nM. The derived 3D-QSAR model shows high predictive ability (q(2) = 0.789 and r(2) = 0.997). Steric (contribution of 43.5%) and electrostatic (50.3%) fields and solvation energy (6.1%) of this novel class of 5-HT(4)R antagonists are relevant descriptors for structure-activity relationships. Computational simulation of the complexes between the benzimidazole-4-carboxamide UCM-21195 (5) and the carboxylate UCM-26995 (21) and a 3D model of the transmembrane domain of the 5-HT(4)R, constructed using the reported crystal structure of rhodopsin, have allowed us to define the molecular details of the ligand-receptor interaction that includes (i) the ionic interaction between the NH group of the protonated piperidine of the ligand and the carboxylate group of Asp(3.32), (ii) the hydrogen bond between the carbonyl oxygen of the ligand and the hydroxyl group of Ser(5.43), (iii) the hydrogen bond between the NH group of Asn(6.55) and the aromatic ring of carboxamides or the ether oxygen of carboxylates, (iv) the interaction of the electron-rich clouds of the aromatic ring of Phe(6.51) and the electron-poor hydrogens of the carbon atoms adjacent to the protonated piperidine nitrogen of the ligand, and (v) the pi-sigma stacking interaction between the benzimidazole system of the ligand and the benzene ring of Tyr(5.38). Moreover, the noticeable increase in potency at the 5-HT(4)R sites, by the introduction of a chloro or bromo atom at the 6-position of the aromatic ring, is attributed to the additional electrostatic and van der

  9. 2D- and 3D-QSAR of tocainide and mexiletine analogues acting as Na(v)1.4 channel blockers.

    PubMed

    Carrieri, Antonio; Muraglia, Marilena; Corbo, Filomena; Pacifico, Concetta

    2009-04-01

    Enantiomeric forms of Tocainide, Mexiletine, and structurally related local anaesthetic compounds, were analyzed with respect to their potency in blocking Na(v)1.4 channel. Structure-activity relationships based on in vitro pharmacological assays, suggested that an increase in terms of lipophilicity and/or molecular surface as well as the presence of specific polar spacers might be determinant for receptor interactions. QSAR and pharmacophore models were then used to support at 3D level this hypothesis. PMID:19027197

  10. 3D-QSAR and docking studies of 3-Pyridine heterocyclic derivatives as potent PI3K/mTOR inhibitors

    NASA Astrophysics Data System (ADS)

    Yang, Wenjuan; Shu, Mao; Wang, Yuanqiang; Wang, Rui; Hu, Yong; Meng, Lingxin; Lin, Zhihua

    2013-12-01

    Phosphoinosmde-3-kinase/ mammalian target of rapamycin (PI3K/mTOR) dual inhibitors have attracted a great deal of interest as antitumor drugs research. In order to design and optimize these dual inhibitors, two types of 3D-quantitative structure-activity relationship (3D-QSAR) studies based on the ligand alignment and receptor alignment were applied using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). In the study based on ligands alignment, models of PI3K (CoMFA with r2, 0.770; q2, 0.622; CoMSIA with r2, 0.945; q2, 0.748) and mTOR (CoMFA with r2, 0.850; q2, 0.654; CoMSIA with r2, 0.983; q2, 0.676) have good predictability. And in the study based on receptor alignment, models of PI3K (CoMFA with r2, 0.745; q2, 0.538; CoMSIA with r2, 0.938; q2, 0.630) and mTOR (CoMFA with r2, 0.977; q2, 0.825; CoMSIA with r2, 0.985; q2, 0.728) also have good predictability. 3D contour maps and docking results suggested different groups on the core parts of the compounds could enhance the biological activities. Finally, ten derivatives as potential candidates of PI3K/mTOR inhibitors with good predicted activities were designed.

  11. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model

    PubMed Central

    Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

    2016-01-01

    Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q2) value of 0.597 and correlation coefficients (r2) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q2 and r2 of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r2pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity. PMID:27144563

  12. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model.

    PubMed

    Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

    2016-01-01

    Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q²) value of 0.597 and correlation coefficients (r²) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q² and r² of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r²pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity. PMID:27144563

  13. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs

    PubMed Central

    Shiri, Fereshteh; Pirhadi, Somayeh; Ghasemi, Jahan B.

    2015-01-01

    Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD) and the enhanced replacement method (ERM) were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND) approach. After variable selection, GRIND were correlated with activity values (pIC50) by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q2 value of 0.77, an rpred2 of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap) implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors. PMID:27013913

  14. Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives.

    PubMed

    Xu, Feng; Yang, Zhen-Zhen; Ke, Zhong-Lu; Xi, Li-Min; Yan, Qi-Dong; Yang, Wei-Qiang; Zhu, Li-Qing; Lin, Fei-Lei; Lv, Wei-Ke; Wu, Han-Gui; Wang, John; Li, Hai-Bo

    2016-10-01

    A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and their structures were confirmed by single-crystal X-ray diffraction. Compared to some reported structures of 1,6-dihydro-1,2,4,5-tetrazine, these compounds can't be considered as having homoaromaticity. Their antiproliferative activities were evaluated against MCF-7, Bewo and HL-60 cells in vitro. Two compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 0.63-13.12μM. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 51 [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives with antiproliferative activity against MCF-7 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.716 and 0.723, respectively. Conventional r(2) values were 0.985 and 0.976, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives. PMID:27597251

  15. 3D QSAR based design of novel oxindole derivative as 5HT7 inhibitors.

    PubMed

    Chitta, Aparna; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-06-01

    To understand the structural requirements of 5-hydroxytryptamine (5HT7) receptor inhibitors and to design new ligands against 5HT7 receptor with enhanced inhibitory potency, a three-dimensional quantitative structure-activity relationship study with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a data set of 56 molecules consisting of oxindole, tetrahydronaphthalene, aryl ketone substituted arylpiperazinealkylamide derivatives was performed. Derived model showed good statistical reliability in terms of predicting 5HT7 inhibitory activity of the molecules, based on molecular property fields like steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. This is evident from statistical parameters like conventional r2 and a cross validated (q2) values of 0.985, 0.743 for CoMFA and 0.970, 0.608 for CoMSIA, respectively. Predictive ability of the models to determine 5HT7 antagonistic activity is validated using a test set of 16 molecules that were not included in the training set. Predictive r2 obtained for the test set was 0.560 and 0.619 for CoMFA and CoMSIA, respectively. Steric, electrostatic fields majorly contributed toward activity which forms the basis for design of new molecules. Absorption, distribution, metabolism and elimination (ADME) calculation using QikProp 2.5 (Schrodinger 2010, Portland, OR) reveals that the molecules confer to Lipinski's rule of five in majority of the cases.

  16. Studies on [5,6]-Fused Bicyclic Scaffolds Derivatives as Potent Dual B-RafV600E/KDR Inhibitors Using Docking and 3D-QSAR Approaches

    PubMed Central

    Liu, Hai-Chun; Tang, San-Zhi; Lu, Shuai; Ran, Ting; Wang, Jian; Zhang, Yan-Min; Xu, An-Yang; Lu, Tao; Chen, Ya-Dong

    2015-01-01

    Research and development of multi-target inhibitors has attracted increasing attention as anticancer therapeutics. B-RafV600E synergistically works with vascular endothelial growth factor receptor 2 (KDR) to promote the occurrence and progression of cancers, and the development of dual-target drugs simultaneously against these two kinds of kinase may offer a better treatment advantage. In this paper, docking and three-dimensional quantitative structure activity relationship (3D-QSAR) studies were performed on a series of dual B-Raf/KDR inhibitors with a novel hinge-binding group, [5,6]-fused bicyclic scaffold. Docking studies revealed optimal binding conformations of these compounds interacting with both B-Raf and KDR. Based on these conformations, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) 3D-QSAR models were constructed, and the best CoMFA (q2 = 0.542, r2 = 0.989 for B-Raf; q2 = 0.768, r2 = 0.991 for KDR) and CoMSIA models (q2 = 0.519, r2 = 0.992 for B-Raf; q2 = 0.849, r2 = 0.993 for KDR) were generated. Further external validations confirmed their predictability, yielding satisfactory correlation coefficients (r2pred = 0.764 (CoMFA), r2pred = 0.841 (CoMSIA) for B-Raf, r2pred = 0.912 (CoMFA), r2pred = 0.846 (CoMSIA) for KDR, respectively). Through graphical analysis and comparison on docking results and 3D-QSAR contour maps, key amino acids that affect the ligand-receptor interactions were identified and structural features influencing the activities were discussed. New potent derivatives were designed, and subjected to preliminary pharmacological evaluation. The study may offer useful references for the modification and development of novel dual B-Raf/KDR inhibitors. PMID:26501259

  17. A combination of pharmacophore modeling, atom-based 3D-QSAR, molecular docking and molecular dynamics simulation studies on PDE4 enzyme inhibitors.

    PubMed

    Tripuraneni, Naga Srinivas; Azam, Mohammed Afzal

    2016-11-01

    Phosphodiesterases 4 enzyme is an attractive target for the design of anti-inflammatory and bronchodilator agents. In the present study, pharmacophore and atom-based 3D-QSAR studies were carried out for pyrazolopyridine and quinoline derivatives using Schrödinger suite 2014-3. A four-point pharmacophore model was developed using 74 molecules having pIC50 ranging from 10.1 to 4.5. The best four feature model consists of one hydrogen bond acceptor, two aromatic rings, and one hydrophobic group. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a high correlation coefficient (R(2 )= .9949), cross validation coefficient (Q(2 )= .7291), and Pearson-r (.9107) at six component partial least square factor. The external validation indicated that our QSAR model possessed high predictive power with R(2) value of .88. The generated model was further validated by enrichment studies using the decoy test. Molecular docking, free energy calculation, and molecular dynamics (MD) simulation studies have been performed to explore the putative binding modes of these ligands. A 10-ns MD simulation confirmed the docking results of both stability of the 1XMU-ligand complex and the presumed active conformation. Outcomes of the present study provide insight in designing novel molecules with better PDE4 inhibitory activity.

  18. Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's disease.

    PubMed

    Zhou, An; Hu, Jianping; Wang, Lirong; Zhong, Guochen; Pan, Jian; Wu, Zeyu; Hui, Ailing

    2015-10-01

    Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552 and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green).

  19. The discovery of a novel and selective inhibitor of PTP1B over TCPTP: 3D QSAR pharmacophore modeling, virtual screening, synthesis, and biological evaluation.

    PubMed

    Ma, Ying; Jin, Yuan-Yuan; Wang, Ye-Liu; Wang, Run-Ling; Lu, Xin-Hua; Kong, De-Xin; Xu, Wei-Ren

    2014-06-01

    Given the special role of insulin and leptin signaling in various biological responses, protein-tyrosine phosphatase-1B (PTP1B) was regarded as a novel therapeutic target for treating type 2 diabetes and obesity. However, owing to the highly conserved (sequence identity of about 74%) in active pocket, targeting PTP1B for drug discovery is a great challenge. In this study, we employed the software package Discovery Studio to develop 3D QSAR pharmacophore models for PTP1B and TCPTP inhibitors. It was further validated by three methods (cost analysis, test set prediction, and Fisher's test) to show that the models can be used to predict the biological activities of compounds without costly and time-consuming synthesis. The criteria for virtual screening were also validated by testing the selective PTP1B inhibitors. Virtual screening experiments and subsequent in vitro evaluation of promising hits revealed a novel and selective inhibitor of PTP1B over TCPTP. After that, a most likely binding mode was proposed. Thus, the findings reported here may provide a new strategy in discovering selective PTP1B inhibitors.

  20. Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore Approaches.

    PubMed

    Lee, Sehan; Barron, Mace G

    2015-11-01

    Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the neurotransmitter acetylcholine in animals, has been used as a target for drugs and pesticides. With the increasing availability of AChE crystal structures, with or without ligands bound, structure-based approaches have been successfully applied to AChE inhibitors (AChEIs). The major limitation of these approaches has been the small applicability domain due to the lack of structural diversity in the training set. In this study, we developed a 3 dimensional quantitative structure-activity relationship (3D-QSAR) for inhibitory activity of 89 reversible and irreversible AChEIs including drugs and insecticides. A 3D-fingerprint descriptor encoding protein-ligand interactions was developed using molecular docking and structure-based pharmacophore to rationalize the structural requirements responsible for the activity of these compounds. The obtained 3D-QSAR model exhibited high correlation value (R(2) = 0.93) and low mean absolute error (MAE = 0.32 log units) for the training set (n = 63). The model was predictive across a range of structures as shown by the leave-one-out cross-validated correlation coefficient (Q(2) = 0.89) and external validation results (n = 26, R(2) = 0.89, and MAE = 0.38 log units). The model revealed that the compounds with high inhibition potency had proper conformation in the active site gorge and interacted with key amino acid residues, in particular Trp84 and Phe330 at the catalytic anionic site, Trp279 at the peripheral anionic site, and Gly118, Gly119, and Ala201 at the oxyanion hole. The resulting universal 3D-QSAR model provides insight into the multiple molecular interactions determining AChEI potency that may guide future chemical design and regulation of toxic AChEIs.

  1. Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore Approaches.

    PubMed

    Lee, Sehan; Barron, Mace G

    2015-11-01

    Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the neurotransmitter acetylcholine in animals, has been used as a target for drugs and pesticides. With the increasing availability of AChE crystal structures, with or without ligands bound, structure-based approaches have been successfully applied to AChE inhibitors (AChEIs). The major limitation of these approaches has been the small applicability domain due to the lack of structural diversity in the training set. In this study, we developed a 3 dimensional quantitative structure-activity relationship (3D-QSAR) for inhibitory activity of 89 reversible and irreversible AChEIs including drugs and insecticides. A 3D-fingerprint descriptor encoding protein-ligand interactions was developed using molecular docking and structure-based pharmacophore to rationalize the structural requirements responsible for the activity of these compounds. The obtained 3D-QSAR model exhibited high correlation value (R(2) = 0.93) and low mean absolute error (MAE = 0.32 log units) for the training set (n = 63). The model was predictive across a range of structures as shown by the leave-one-out cross-validated correlation coefficient (Q(2) = 0.89) and external validation results (n = 26, R(2) = 0.89, and MAE = 0.38 log units). The model revealed that the compounds with high inhibition potency had proper conformation in the active site gorge and interacted with key amino acid residues, in particular Trp84 and Phe330 at the catalytic anionic site, Trp279 at the peripheral anionic site, and Gly118, Gly119, and Ala201 at the oxyanion hole. The resulting universal 3D-QSAR model provides insight into the multiple molecular interactions determining AChEI potency that may guide future chemical design and regulation of toxic AChEIs. PMID:26202430

  2. A combined pharmacophore modeling, 3D-QSAR and molecular docking study of substituted bicyclo-[3.3.0]oct-2-enes as liver receptor homolog-1 (LRH-1) agonists

    NASA Astrophysics Data System (ADS)

    Lalit, Manisha; Gangwal, Rahul P.; Dhoke, Gaurao V.; Damre, Mangesh V.; Khandelwal, Kanchan; Sangamwar, Abhay T.

    2013-10-01

    A combined pharmacophore modelling, 3D-QSAR and molecular docking approach was employed to reveal structural and chemical features essential for the development of small molecules as LRH-1 agonists. The best HypoGen pharmacophore hypothesis (Hypo1) consists of one hydrogen-bond donor (HBD), two general hydrophobic (H), one hydrophobic aromatic (HYAr) and one hydrophobic aliphatic (HYA) feature. It has exhibited high correlation coefficient of 0.927, cost difference of 85.178 bit and low RMS value of 1.411. This pharmacophore hypothesis was cross-validated using test set, decoy set and Cat-Scramble methodology. Subsequently, validated pharmacophore hypothesis was used in the screening of small chemical databases. Further, 3D-QSAR models were developed based on the alignment obtained using substructure alignment. The best CoMFA and CoMSIA model has exhibited excellent rncv2 values of 0.991 and 0.987, and rcv2 values of 0.767 and 0.703, respectively. CoMFA predicted rpred2 of 0.87 and CoMSIA predicted rpred2 of 0.78 showed that the predicted values were in good agreement with the experimental values. Molecular docking analysis reveals that π-π interaction with His390 and hydrogen bond interaction with His390/Arg393 is essential for LRH-1 agonistic activity. The results from pharmacophore modelling, 3D-QSAR and molecular docking are complementary to each other and could serve as a powerful tool for the discovery of potent small molecules as LRH-1 agonists.

  3. 3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase

    NASA Astrophysics Data System (ADS)

    Li, Wenlian; Si, Hongzong; Li, Yang; Ge, Cuizhu; Song, Fucheng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-08-01

    Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion and hepatitis C virus (HCV) infection is a global health threat. The HCV NS5B polymerase, an RNA dependent RNA polymerase (RdRp) and an essential role in the replication of the virus, has no functional equivalent in mammalian cells. So the research and development of efficient NS5B polymerase inhibitors provides a great strategy for antiviral therapy against HCV. A combined three-dimensional quantitative structure-activity relationship (QSAR) modeling was accomplished to profoundly understand the structure-activity correlation of a train of indole-based inhibitors of the HCV NS5B polymerase to against HCV. A comparative molecular similarity indices analysis (COMSIA) model as the foundation of the maximum common substructure alignment was developed. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient q2 was 0.627 and non-cross-validated r2 value was 0.943. In addition, the results of internal validations of bootstrapping and Y-randomization confirmed the rationality and good predictive ability of the model, as well as external validation (the external predictive correlation coefficient rext2 = 0.629). The information obtained from the COMSIA contour maps enables the interpretation of their structure-activity relationship. Furthermore, the molecular docking study of the compounds for 3TYV as the protein target revealed important interactions between active compounds and amino acids, and several new potential inhibitors with higher activity predicted were designed basis on our analyses and supported by the simulation of molecular docking. Meanwhile, the OSIRIS Property Explorer was introduced to help select more satisfactory compounds. The satisfactory results from this study may lay a reliable theoretical base for drug development of hepatitis C virus NS5B polymerase inhibitors.

  4. Molecular docking, molecular dynamics simulation, and structure-based 3D-QSAR studies on estrogenic activity of hydroxylated polychlorinated biphenyls.

    PubMed

    Li, Xiaolin; Ye, Li; Wang, Xiaoxiang; Wang, Xinzhou; Liu, Hongling; Qian, Xiangping; Zhu, Yongliang; Yu, Hongxia

    2012-12-15

    Hydroxylated polychlorinated biphenyls (HO-PCBs), major metabolites of PCBs, have been reported to present agonist or antagonist interactions with estrogen receptor α (ERα) and induce ER-mediated responses. In this work, a multistep framework combining molecular docking, molecular dynamics (MD) simulations, and structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed to explore the influence of structural features on the estrogenic activities of HO-PCBs, and to investigate the molecular mechanism of ERα-ligand interactions. The CoMSIA (comparative molecular similarity indices analysis) model was developed from the conformations obtained from molecular docking. The model exhibited statistically significant results as the cross-validated correlation coefficient q² was 0.648, the non-cross-validated correlation coefficient r² was 0.968, and the external predictive correlation coefficient r(pred)² was 0.625. The key amino acid residues were identified by molecular docking, and the detailed binding modes of the compounds with different activities were determined by MD simulations. The binding free energies correlated well with the experimental activity. An energetic analysis, MM-GBSA energy decomposition, revealed that the van der Waals interaction was the major driving force for the binding of compounds to ERα. The hydrogen bond interactions between the ligands and residue His524 help to stabilize the conformation of ligands at the binding pocket. These results are expected to be beneficial to predict estrogenic activities of other HO-PCB congeners and helpful for understanding the binding mechanism of HO-PCBs and ERα. PMID:23137989

  5. De novo design of N-(pyridin-4-ylmethyl)aniline derivatives as KDR inhibitors: 3D-QSAR, molecular fragment replacement, protein-ligand interaction fingerprint, and ADMET prediction.

    PubMed

    Zhang, Yanmin; Liu, Haichun; Jiao, Yu; Yuan, Haoliang; Wang, Fengxiao; Lu, Shuai; Yao, Sihui; Ke, Zhipeng; Tai, Wenting; Jiang, Yulei; Chen, Yadong; Lu, Tao

    2012-11-01

    Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2 or kinase insert domain receptor (KDR) have been identified as promising targets for novel anticancer agents. To achieve new potent inhibitors of KDR, we conducted molecular fragment replacement (MFR) studies for the understanding of 3D-QSAR modeling and the docking investigation of arylphthalazines and 2-((1H-Azol-1-yl)methyl)-N-arylbenzamides-based KDR inhibitors. Two favorable 3D-QSAR models (CoMFA with q(2), 0.671; r(2), 0.969; CoMSIA with q(2), 0.608; r(2), 0.936) have been developed to predict the biological activity of new compounds. The new molecular database generated by MFR was virtually screened using Glide (docking) and further evaluated with CoMFA prediction, protein-ligand interaction fingerprint (PLIF) and ADMET analysis. 44 N-(pyridin-4-ylmethyl)aniline derivatives as novel potential KDR inhibitors were finally obtained. In this paper, the work flow developed could be applied to de novo drug design and virtual screening potential KDR inhibitors, and use hit compounds to further optimize and design new potential KDR inhibitors.

  6. A 3D-QSAR model based screen for dihydropyridine-like compound library to identify inhibitors of amyloid beta (Aβ) production.

    PubMed

    Mathura, Venkatarajan S; Patel, Nikunj; Bachmeier, Corbin; Mullan, Michael; Paris, Daniel

    2010-01-01

    Abnormal accumulation of amyloid beta peptide (Aβ) is one of the hallmarks of Alzheimer's disease progression. Practical limitations such as cost , poor hit rates and a lack of well characterized targets are a major bottle neck in the in vitro screening of a large number of chemical libraries and profiling them to identify Aβ inhibitors. We used a limited set of 1,4 dihydropyridine (DHP)-like compounds from our model set (MS) of 24 compounds which inhibit Aβ as a training set and built 3D-QSAR (Three-dimensional Quantitative Structure-Activity Relationship) models using the Phase program (SchrÖdinger, USA). We developed a 3D-QSAR model that showed the best prediction for Aβ inhibition in the test set of compounds and used this model to screen a 1,043 DHP-like small library set of (LS) compounds. We found that our model can effectively predict potent hits at a very high rate and result in significant cost savings when screening larger libraries. We describe here our in silico model building strategy, model selection parameters and the chemical features that are useful for successful screening of DHP and DHP-like chemical libraries for Aβ inhibitors. PMID:21364791

  7. Chemical proteomic tool for ligand mapping of CYP antitargets: an NMR-compatible 3D QSAR descriptor in the Heme-Based Coordinate System.

    PubMed

    Yao, Huili; Costache, Aurora D; Sem, Daniel S

    2004-01-01

    Chemical proteomic strategies strive to probe and understand protein-ligand interactions across gene families. One gene family of particular interest in drug and xenobiotic metabolism are the cytochromes P450 (CYPs), the topic of this article. Although numerous tools exist to probe affinity of CYP-ligand interactions, fewer exist for the rapid experimental characterization of the structural nature of these interactions. As a complement to recent advances in X-ray crystallography, NMR methods are being developed that allow for fairly high throughput characterization of protein-ligand interactions. One especially promising NMR approach involves the use of paramagnetic induced relaxation effects to measure distances of ligand atoms from the heme iron in CYP enzymes. Distances obtained from these T(1) relaxation measurements can be used as a direct source of 1-dimensional structural information or to restrain a ligand docking to generate a 3-dimensional data set. To facilitate such studies, we introduce the concept of the Heme-Based Coordinate System and present how it can be used in combination with NMR T(1) relaxation data to derive 3D QSAR descriptors directly or in combination with in silico docking. These descriptors should have application in defining the binding preferences of CYP binding sites using 3D QSAR models. They are especially well-suited for the biasing of fragment assembly and combinatorial chemistry drug design strategies, to avoid fragment or reagent combinations with enhanced affinity for CYP antitargets.

  8. Molecular modeling studies on series of Btk inhibitors using docking, structure-based 3D-QSAR and molecular dynamics simulation: a combined approach.

    PubMed

    Balasubramanian, Pavithra K; Balupuri, Anand; Cho, Seung Joo

    2016-03-01

    Bruton tyrosine kinase (Btk) is a non-receptor tyrosine kinase. It is a crucial component in BCR pathway and expressed only in hematopoietic cells except T cells and Natural killer cells. BTK is a promising target because of its involvement in signaling pathways and B cell diseases such as autoimmune disorders and lymphoma. In this work, a combined molecular modeling study of molecular docking, 3D-QSAR and molecular dynamic (MD) simulation were performed on a series of 2,5-diaminopyrimidine compounds as inhibitors targeting Btk kinase to understand the interaction and key residues involved in the inhibition. A structure based CoMFA (q (2) = 0.675, NOC = 5, r (2) = 0.961) and COMSIA (q (2) = 0.704, NOC = 6, r (2) = 0.962) models were developed from the conformation obtained by docking. The developed models were subjected to various validation techniques such as leave-five-out, external test set, bootstrapping, progressive sampling and rm (2) metrics and found to have a good predictive ability in both internal and external validation. Our docking results showed the important residues that interacts in the active site residues in inhibition of Btk kinase. Furthermore, molecular dynamics simulation was employed to study the stability of the docked conformation and to investigate the binding interactions in detail. The MD simulation analyses identified several important hydrogen bonds with Btk, including the gatekeeper residue Thr474 and Met477 at the hinge region. Hydrogen bond with active site residues Leu408 and Arg525 were also recognized. A good correlation between the MD results, docking studies and the contour map analysis are observed. This indicates that the developed models are reliable. Our results from this study can provide insights in the designing and development of more potent Btk kinase inhibitors.

  9. In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations.

    PubMed

    Gao, Xiaodong; Han, Liping; Ren, Yujie

    2016-01-01

    Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q² values (0.531, 0.726), fitted correlation r² coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity. PMID:27164065

  10. Structural and chemical basis for enhanced affinity and potency for a large series of estrogen receptor ligands: 2D and 3D QSAR studies.

    PubMed

    Salum, Lívia de B; Polikarpov, Igor; Andricopulo, Adriano D

    2007-09-01

    The estrogen receptor (ER) is an important drug target for the development of novel therapeutic agents for the treatment of breast cancer. Progress towards the design of more potent and selective ER modulators requires the optimization of multiple ligand-receptor interactions. Comparative molecular field analyses (CoMFA) and hologram quantitative structure-activity relationships (HQSAR) were conducted on a large set of ERalpha modulators. Two training sets containing either 127 or 69 compounds were used to generate QSAR models for in vitro binding affinity and potency, respectively. Significant correlation coefficients (affinity models, CoMFA, r(2)=0.93 and q(2)=0.79; HQSAR, r(2)=0.92 and q(2)=0.71; potency models, CoMFA, r(2)=0.94 and q(2)=0.72; HQSAR, r(2)=0.92 and q(2)=0.74) were obtained, indicating the potential of the models for untested compounds. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel ERalpha modulators having improved affinity and potency.

  11. Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H-pyrazole niacinamide derivatives as BRAF inhibitors.

    PubMed

    Li, Cui-Yun; Li, Qing-Shan; Yan, Li; Sun, Xiao-Guang; Wei, Ran; Gong, Hai-Bin; Zhu, Hai-Liang

    2012-06-15

    A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. Results of the bioassays against BRAF(V600E) and WM266.4 human melanoma cell line showed several compounds to be endowed potent activities with IC(50) and GI(50) value in low micromolar range, among which compound 27e, (5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3-yl methanone (IC(50)=0.20 μM, GI(50)=0.89 μM) was bearing the best bioactivity comparable with the positive control Sorafenib. Docking simulation was performed to determine the probable binding model and 3D-QSAR model was built to provide more pharmacophore understanding that could use to design new agents with more potent BRAF(V600E) inhibitory activity.

  12. 3D face analysis for demographic biometrics

    SciTech Connect

    Tokola, Ryan A; Mikkilineni, Aravind K; Boehnen, Chris Bensing

    2015-01-01

    Despite being increasingly easy to acquire, 3D data is rarely used for face-based biometrics applications beyond identification. Recent work in image-based demographic biometrics has enjoyed much success, but these approaches suffer from the well-known limitations of 2D representations, particularly variations in illumination, texture, and pose, as well as a fundamental inability to describe 3D shape. This paper shows that simple 3D shape features in a face-based coordinate system are capable of representing many biometric attributes without problem-specific models or specialized domain knowledge. The same feature vector achieves impressive results for problems as diverse as age estimation, gender classification, and race classification.

  13. Pharmacophore and 3D-QSAR characterization of 6-arylquinazolin-4-amines as Cdc2-like kinase 4 (Clk4) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) inhibitors.

    PubMed

    Pan, Yongmei; Wang, Yanli; Bryant, Stephen H

    2013-04-22

    Cdc2-like kinase 4 (Clk4) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) are protein kinases that are promising targets for treatment of diseases caused by abnormal gene splicing. 6-Arylquinazolin-4-amines have been recently identified as potent Clk4 and Dyrk1A inhibitors. In order to understand the structure-activity correlation of these analogs, we have applied ligand-based pharmacophore and 3D-QSAR modeling combined with structure-based homology modeling and docking. The high R(2) and Q(2) (0.88 and 0.79 for Clk4, 0.85 and 0.82 for Dyrk1A, respectively) based on validation with training and test set compounds suggested that the generated 3D-QSAR models are reliable in predicting novel ligand activities against Clk4 and Dyrk1A. The binding mode identified through docking ligands to the ATP binding domain of Clk4 was consistent with the structural properties and energy field contour maps characterized by pharmacophore and 3D-QSAR models and gave valuable insights into the structure-activity profile of 6-arylquinazolin-4-amine analogs. The obtained 3D-QSAR and pharmacophore models in combination with the binding mode between inhibitor and residues of Clk4 will be helpful for future lead compound identification and optimization to design potent and selective Clk4 and Dyrk1A inhibitors. PMID:23496085

  14. Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies.

    PubMed

    Nikolic, Katarina; Mavridis, Lazaros; Djikic, Teodora; Vucicevic, Jelica; Agbaba, Danica; Yelekci, Kemal; Mitchell, John B O

    2016-01-01

    HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands

  15. Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies

    PubMed Central

    Nikolic, Katarina; Mavridis, Lazaros; Djikic, Teodora; Vucicevic, Jelica; Agbaba, Danica; Yelekci, Kemal; Mitchell, John B. O.

    2016-01-01

    HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer‘s disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a “predictor” model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent

  16. 3D joint dynamics analysis of healthy children's gait.

    PubMed

    Samson, William; Desroches, Guillaume; Cheze, Laurence; Dumas, Raphaël

    2009-11-13

    The 3D joint moments and 2D joint powers have been largely explored in the literature of healthy children's gait, in particular to compare them with pathologic subjects' gait. However, no study reported on 3D joint power in children which could be due to the difficulties in interpreting the results. Recently, the analysis of the 3D angle between the joint moment and the joint angular velocity vectors has been proposed in order to help 3D joint power interpretation. Our hypothesis is that this 3D angle may help in characterizing the level of gait maturation. The present study explores 3D joint moments, 3D joint power and the proposed 3D angle for both children's and adults' gaits to highlight differences in the strategies used. The results seem to confirm that children have an alternative strategy of mainly ankle stabilization and hip propulsion compared to the adults' strategy of mainly ankle resistance and propulsion and hip stabilization. In the future, the same 3D angle analysis should be applied to different age groups for better describing the evolution of the 3D joint dynamic strategies during the growth.

  17. 3D-QSAR and molecular docking study of LRRK2 kinase inhibitors by CoMFA and CoMSIA methods.

    PubMed

    Pourbasheer, E; Aalizadeh, R

    2016-05-01

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) modelling was conducted on a series of leucine-rich repeat kinase 2 (LRRK2) antagonists using CoMFA and CoMSIA methods. The data set, which consisted of 37 molecules, was divided into training and test subsets by using a hierarchical clustering method. Both CoMFA and CoMSIA models were derived using a training set on the basis of the common substructure-based alignment. The optimum PLS model built by CoMFA and CoMSIA provided satisfactory statistical results (q(2) = 0.589 and r(2) = 0.927 and q(2) = 0.473 and r(2) = 0.802, respectively). The external predictive ability of the models was evaluated by using seven compounds. Moreover, an external evaluation set with known experimental data was used to evaluate the external predictive ability of the porposed models. The statistical parameters indicated that CoMFA (after region focusing) has high predictive ability in comparison with standard CoMFA and CoMSIA models. Molecular docking was also performed on the most active compound to investigate the existence of interactions between the most active inhibitor and the LRRK2 receptor. Based on the obtained results and CoMFA contour maps, some features were introduced to provide useful insights for designing novel and potent LRRK2 inhibitors. PMID:27228480

  18. Identification of Potent Virtual Leads Specific to S1' Loop of ADAMTS4: Pharmacophore Modeling, 3D-QSAR, Molecular Docking and Dynamic Studies.

    PubMed

    Suganya, P Rathi; Kalva, Sukesh; Saleena, Lilly M

    2016-01-01

    ADAMTS4 (Aggrecanase-1) is an important enzyme, which belongs to ADAMTS family. Aggrecanase-1 is involved in aggrecan degradation of articular cartilage in osteoarthritis and rheumatoid arthritis. Overall variability of S1' domain of ADAMTS4 has been the main selectivity determinant to design the unique inhibitors. 34 inhibitors from Binding database and literature were used to develop the pharmacophore model. The five featured pharmacophore model AHHRR had the best survival score of 3.493 and post-hoc score of 2.545, indicating that the model is highly reliable. The 3D-QSAR acquired had excellent r(2) value of 0.99 and GH score of 0.839. The validated pharmacophore model was used for insilico screening of Asinex and ZINC database for finding the potential lead compounds. ZINC00987406 and ASN04459656 which pose high glide score i.e >7 Kcal/mol and H-bond and hydrophobic interactions in the S1'loop residues of ADAMTS4 were subjected to Molecular Dynamics Simulation studies. Molecular dynamic simulation result indicates that the RMSD and RMSF of backbone atoms for the above complexes were within the limit of 2.0 A˚. These compounds can be potential candidates for osteoarthritis by inhibiting ADAMTS4. PMID:26813685

  19. Design, biological evaluation and 3D QSAR studies of novel dioxin-containing triaryl pyrazoline derivatives as potential B-Raf inhibitors.

    PubMed

    Yang, Yu-Shun; Yang, Bing; Zou, Yan; Li, Guigen; Zhu, Hai-Liang

    2016-07-01

    A series of novel dioxin-containing triaryl pyrazoline derivatives C1-C20 have been synthesized. Their B-Raf inhibitory and anti-proliferation activities were evaluated. Compound C6 displayed the most potent biological activity against B-Raf(V600E) and WM266.4 human melanoma cell line with corresponding IC50 value of 0.04μM and GI50 value of 0.87μM, being comparable with the positive controls and more potent than our previous best compounds. Moreover, C6 was selective for B-Raf(V600E) from B-Raf(WT), C-Raf and EGFR and low toxic. The docking simulation suggested the potent bioactivity might be caused by breaking the limit of previous binding pattern. A new 3D QSAR model was built with the activity data and binding conformations to conduct visualized SAR discussion as well as to introduce new directions. Stretching the backbone to outer space or totally reversing the backbone are both potential orientations for future researches. PMID:27238841

  20. Elucidating the structural basis of diphenyl ether derivatives as highly potent enoyl-ACP reductase inhibitors through molecular dynamics simulations and 3D-QSAR study.

    PubMed

    Kamsri, Pharit; Punkvang, Auradee; Saparpakorn, Patchareenart; Hannongbua, Supa; Irle, Stephan; Pungpo, Pornpan

    2014-07-01

    Diphenyl ether derivatives are good candidates for anti-tuberculosis agents that display a promising potency for inhibition of InhA, an essential enoyl-acyl carrier protein (ACP) reductase involved in fatty acid biosynthesis pathways in Mycobacterium tuberculosis. In this work, key structural features for the inhibition were identified by 3D-QSAR CoMSIA models, constructed based on available experimental binding properties of diphenyl ether inhibitors, and a set of four representative compounds was subjected to MD simulations of inhibitor-InhA complexes for the calculation of binding free energies. The results show that bulky groups are required for the R1 substituent on the phenyl A ring of the inhibitors to favor a hydrophobic pocket formed by residues Phe149, Met155, Pro156, Ala157, Tyr158, Pro193, Met199, Val203, Leu207, Ile215, and Leu218. Small substituents with a hydrophilic property are required at the R3 and R4 positions of the inhibitor phenyl B rings to form hydrogen bonds with the backbones of Gly96 and Met98, respectively. For the R2 substituent, small substituents with simultaneous hydrophilic or hydrophobic properties are required to favor the interaction with the pyrophosphate moiety of NAD(+) and the methyl side chain of Ala198, respectively. The reported data provide structural guidance for the design of new and potent diphenyl ether-based inhibitors with high inhibitory activities against M. tuberculosis InhA. PMID:24935113

  1. Elucidating the structural basis of diphenyl ether derivatives as highly potent enoyl-ACP reductase inhibitors through molecular dynamics simulations and 3D-QSAR study.

    PubMed

    Kamsri, Pharit; Punkvang, Auradee; Saparpakorn, Patchareenart; Hannongbua, Supa; Irle, Stephan; Pungpo, Pornpan

    2014-07-01

    Diphenyl ether derivatives are good candidates for anti-tuberculosis agents that display a promising potency for inhibition of InhA, an essential enoyl-acyl carrier protein (ACP) reductase involved in fatty acid biosynthesis pathways in Mycobacterium tuberculosis. In this work, key structural features for the inhibition were identified by 3D-QSAR CoMSIA models, constructed based on available experimental binding properties of diphenyl ether inhibitors, and a set of four representative compounds was subjected to MD simulations of inhibitor-InhA complexes for the calculation of binding free energies. The results show that bulky groups are required for the R1 substituent on the phenyl A ring of the inhibitors to favor a hydrophobic pocket formed by residues Phe149, Met155, Pro156, Ala157, Tyr158, Pro193, Met199, Val203, Leu207, Ile215, and Leu218. Small substituents with a hydrophilic property are required at the R3 and R4 positions of the inhibitor phenyl B rings to form hydrogen bonds with the backbones of Gly96 and Met98, respectively. For the R2 substituent, small substituents with simultaneous hydrophilic or hydrophobic properties are required to favor the interaction with the pyrophosphate moiety of NAD(+) and the methyl side chain of Ala198, respectively. The reported data provide structural guidance for the design of new and potent diphenyl ether-based inhibitors with high inhibitory activities against M. tuberculosis InhA.

  2. New approach to pharmacophore mapping and QSAR analysis using inductive logic programming. Application to thermolysin inhibitors and glycogen phosphorylase B inhibitors.

    PubMed

    Marchand-Geneste, Nathalie; Watson, Kimberly A; Alsberg, Bjørn K; King, Ross D

    2002-01-17

    A key problem in QSAR is the selection of appropriate descriptors to form accurate regression equations for the compounds under study. Inductive logic programming (ILP) algorithms are a class of machine-learning algorithms that have been successfully applied to a number of SAR problems. Unlike other QSAR methods, which use attributes to describe chemical structure, ILP uses relations. This gives ILP the advantages of not requiring explicit superimposition of individual compounds in a dataset, of dealing naturally with multiple conformations, and of using a language much closer to that used normally by chemists. We unify ILP and standard regression techniques to give a QSAR method that has the strength of ILP at describing steric structure with the familiarity and power of regression methods. Complex pharmacophores, correlating with activity, were identified and used as new indicator variables, along with the comparative molecular field analysis (CoMFA) prediction, to form predictive regression equations. We compared the formation of 3D-QSARs using standard CoMFA with the use of ILP on the well-studied thermolysin zinc protease inhibitor dataset and a glycogen phosphorylase inhibitor dataset. In each case the addition of ILP variables produced statistically better results (P < 0.01 for thermolysin and P < 0.05 for GP datasets) than the CoMFA analysis. Moreover, the new ILP variables were not found to increase the complexity of the final QSAR equations and gave possible insight into the binding mechanism of the ligand-protein complex under study.

  3. Treating chemical diversity in QSAR analysis: modeling diverse HIV-1 integrase inhibitors using 4D fingerprints.

    PubMed

    Iyer, Manisha; Hopfinger, A J

    2007-01-01

    A set of 213 compounds across 12 structurally diverse classes of HIV-1 integrase inhibitors was used to develop and evaluate a combined clustering and QSAR modeling methodology to construct significant, reliable, and robust models for structurally diverse data sets. The trial-descriptor pool for both clustering- and QSAR-model building consisted of 4D fingerprints and classic QSAR descriptors. Clustering was carried out using a combination of the partitioning around medoids method and divisive hierarchical clustering. QSAR models were constructed for members of each cluster by linear-regression fitting and model optimization using the genetic function approximation. The 12 structurally diverse classes of integrase inhbitors were partitioned into five clusters from which corresponding QSAR models, overwhelmingly composed of 4D fingerprint descriptors, were constructed. Analysis of the five QSAR models suggests that three models correspond to structurally diverse inhibitors that likely bind at a common site on integrase characterized by a common inhibitor hydrogen-bond donor, but involving somewhat different alignments and/or poses for the inhibitors of each of the three clusters. The particular alignments for the inhibitors of each of the three QSAR models involve specific distributions of nonpolar groups over the inhibitors. The two other clusters, one for coumarins and the other for depsides and depsidones, lead to QSAR models with less-defined pharmacophores, likely representing an inhibitor binding to a site(s) different from that of the other nine classes of inhibitors. Overall, the clustering and QSAR methodology employed in this study suggests that it can meaningfully partition structurally diverse compounds expressing a common endpoint in such a manner that leads to statistically significant and pharmacologically insightful composite QSAR models. PMID:17661457

  4. Template CoMFA Generates Single 3D-QSAR Models that, for Twelve of Twelve Biological Targets, Predict All ChEMBL-Tabulated Affinities

    PubMed Central

    Cramer, Richard D.

    2015-01-01

    The possible applicability of the new template CoMFA methodology to the prediction of unknown biological affinities was explored. For twelve selected targets, all ChEMBL binding affinities were used as training and/or prediction sets, making these 3D-QSAR models the most structurally diverse and among the largest ever. For six of the targets, X-ray crystallographic structures provided the aligned templates required as input (BACE, cdk1, chk2, carbonic anhydrase-II, factor Xa, PTP1B). For all targets including the other six (hERG, cyp3A4 binding, endocrine receptor, COX2, D2, and GABAa), six modeling protocols applied to only three familiar ligands provided six alternate sets of aligned templates. The statistical qualities of the six or seven models thus resulting for each individual target were remarkably similar. Also, perhaps unexpectedly, the standard deviations of the errors of cross-validation predictions accompanying model derivations were indistinguishable from the standard deviations of the errors of truly prospective predictions. These standard deviations of prediction ranged from 0.70 to 1.14 log units and averaged 0.89 (8x in concentration units) over the twelve targets, representing an average reduction of almost 50% in uncertainty, compared to the null hypothesis of “predicting” an unknown affinity to be the average of known affinities. These errors of prediction are similar to those from Tanimoto coefficients of fragment occurrence frequencies, the predominant approach to side effect prediction, which template CoMFA can augment by identifying additional active structural classes, by improving Tanimoto-only predictions, by yielding quantitative predictions of potency, and by providing interpretable guidance for avoiding or enhancing any specific target response. PMID:26065424

  5. Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy

    PubMed Central

    Jiang, Xueyun; Wang, Yuji; Zhu, Haimei; Wang, Yaonan; Zhao, Ming; Zhao, Shurui; Wu, Jianhui; Li, Shan; Peng, Shiqi

    2015-01-01

    With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydroimidazol-1-yl)-oxyacetyl-L-amino acids (6a–o) were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 μmol/kg 6a–o exhibited excellent oral anti-inflammation and analgesic activity. The dose-dependent assay of their representative 6f indicates that the effective dose should be 3.3 μmol/kg. The correlation of the three-dimensional quantitative structure–activity relationship with the docking analysis provides a basis for the rational design of drugs to treat inflammatory pain. PMID:25960636

  6. MOLECULAR MODELLING, 3D-QSAR, AND DRUG DOCKING STUDIES ON THE ROLE OF NATURAL ANTICOAGULANT COMPOUNDS IN ANTITHROMBOTIC THERAPY

    PubMed Central

    Kakarla, Prathusha; Devireddy, Amith R.; Inupakutika, Madhuri A.; Cheeti, Upender R.; Floyd, Jared T.; Mun, Mukherjee M.; Vigil, Raelyn N.; Hunter, Russell P.; Varela, Manuel F.

    2015-01-01

    Thromboembolic disorders are the leading cause of human mortality. Therefore, development of effective anticoagulant therapy is critical. Factor XIIIA (FXIIIA) protein is a crucial factor in the blood coagulation cascade, and hence it is a vital target for evolution of new antithrombotic agents. Structure-function studies of clotting factor active sites, clot formation, and thrombus structure have gained prominence in the efforts to develop novel anticoagulants. Factor XIIIA was homology modelled with the human transglutaminase-2 crystal structure as a base template for BLAST analysis. Docking and comparative binding site analysis revealed active site residue conservation and inhibitor-protein interactions. Nineteen small molecules possessing suspected anticoagulant properties were successfully docked into the FXIIIA active site following the best CoMFA and CoMSIA prediction values. Dabigatran etexilate was anticipated to be the best FXIIIA inhibitor among the nineteen anticoagulants with the highest binding affinity for the FXIIIA protein and the highest FlexX dock score of −29.8 KJ/mol. Structural properties of FXIIIA inhibitors with increased antithrombotic activity were predicted by this docking study. PMID:25750914

  7. Imaging and 3D morphological analysis of collagen fibrils.

    PubMed

    Altendorf, H; Decencière, E; Jeulin, D; De sa Peixoto, P; Deniset-Besseau, A; Angelini, E; Mosser, G; Schanne-Klein, M-C

    2012-08-01

    The recent booming of multiphoton imaging of collagen fibrils by means of second harmonic generation microscopy generates the need for the development and automation of quantitative methods for image analysis. Standard approaches sequentially analyse two-dimensional (2D) slices to gain knowledge on the spatial arrangement and dimension of the fibrils, whereas the reconstructed three-dimensional (3D) image yields better information about these characteristics. In this work, a 3D analysis method is proposed for second harmonic generation images of collagen fibrils, based on a recently developed 3D fibre quantification method. This analysis uses operators from mathematical morphology. The fibril structure is scanned with a directional distance transform. Inertia moments of the directional distances yield the main fibre orientation, corresponding to the main inertia axis. The collaboration of directional distances and fibre orientation delivers a geometrical estimate of the fibre radius. The results include local maps as well as global distribution of orientation and radius of the fibrils over the 3D image. They also bring a segmentation of the image into foreground and background, as well as a classification of the foreground pixels into the preferred orientations. This accurate determination of the spatial arrangement of the fibrils within a 3D data set will be most relevant in biomedical applications. It brings the possibility to monitor remodelling of collagen tissues upon a variety of injuries and to guide tissues engineering because biomimetic 3D organizations and density are requested for better integration of implants.

  8. The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models.

    PubMed

    Vitorović-Todorović, Maja D; Cvijetić, Ilija N; Juranić, Ivan O; Drakulić, Branko J

    2012-09-01

    The 3D-QSAR analysis based on alignment independent descriptors (GRIND-2) was performed on the set of 110 structurally diverse, dual binding AChE reversible inhibitors. Three separate models were built, based on different conformations, generated following next criteria: (i) minimum energy conformations, (ii) conformation most similar to the co-crystalized ligand conformation, and (iii) docked conformation. We found that regardless on conformation used, all the three models had good statistic and predictivity. The models revealed the importance of protonated pyridine nitrogen of tacrine moiety for anti AChE activity, and recognized HBA and HBD interactions as highly important for the potency. This was revealed by the variables associated with protonated pyridinium nitrogen, and the two amino groups of the linker. MIFs calculated with the N1 (pyridinium nitrogen) and the DRY GRID probes in the AChE active site enabled us to establish the relationship between amino acid residues within AChE active site and the variables having high impact on models. External predictive power of the models was tested on the set of 40 AChE reversible inhibitors, most of them structurally different from the training set. Some of those compounds were tested on the different enzyme source. We found that external predictivity was highly sensitive on conformations used. Model based on docked conformations had superior predictive ability, emphasizing the need for the employment of conformations built by taking into account geometrical restrictions of AChE active site gorge.

  9. 3-D transient analysis of pebble-bed HTGR by TORT-TD/ATTICA3D

    SciTech Connect

    Seubert, A.; Sureda, A.; Lapins, J.; Buck, M.; Bader, J.; Laurien, E.

    2012-07-01

    As most of the acceptance criteria are local core parameters, application of transient 3-D fine mesh neutron transport and thermal hydraulics coupled codes is mandatory for best estimate evaluations of safety margins. This also applies to high-temperature gas cooled reactors (HTGR). Application of 3-D fine-mesh transient transport codes using few energy groups coupled with 3-D thermal hydraulics codes becomes feasible in view of increasing computing power. This paper describes the discrete ordinates based coupled code system TORT-TD/ATTICA3D that has recently been extended by a fine-mesh diffusion solver. Based on transient analyses for the PBMR-400 design, the transport/diffusion capabilities are demonstrated and 3-D local flux and power redistribution effects during a partial control rod withdrawal are shown. (authors)

  10. SAMA: A Method for 3D Morphological Analysis.

    PubMed

    Paulose, Tessie; Montévil, Maël; Speroni, Lucia; Cerruti, Florent; Sonnenschein, Carlos; Soto, Ana M

    2016-01-01

    Three-dimensional (3D) culture models are critical tools for understanding tissue morphogenesis. A key requirement for their analysis is the ability to reconstruct the tissue into computational models that allow quantitative evaluation of the formed structures. Here, we present Software for Automated Morphological Analysis (SAMA), a method by which epithelial structures grown in 3D cultures can be imaged, reconstructed and analyzed with minimum human intervention. SAMA allows quantitative analysis of key features of epithelial morphogenesis such as ductal elongation, branching and lumen formation that distinguish different hormonal treatments. SAMA is a user-friendly set of customized macros operated via FIJI (http://fiji.sc/Fiji), an open-source image analysis platform in combination with a set of functions in R (http://www.r-project.org/), an open-source program for statistical analysis. SAMA enables a rapid, exhaustive and quantitative 3D analysis of the shape of a population of structures in a 3D image. SAMA is cross-platform, licensed under the GPLv3 and available at http://montevil.theobio.org/content/sama. PMID:27035711

  11. SAMA: A Method for 3D Morphological Analysis

    PubMed Central

    Cerruti, Florent; Sonnenschein, Carlos; Soto, Ana M.

    2016-01-01

    Three-dimensional (3D) culture models are critical tools for understanding tissue morphogenesis. A key requirement for their analysis is the ability to reconstruct the tissue into computational models that allow quantitative evaluation of the formed structures. Here, we present Software for Automated Morphological Analysis (SAMA), a method by which epithelial structures grown in 3D cultures can be imaged, reconstructed and analyzed with minimum human intervention. SAMA allows quantitative analysis of key features of epithelial morphogenesis such as ductal elongation, branching and lumen formation that distinguish different hormonal treatments. SAMA is a user-friendly set of customized macros operated via FIJI (http://fiji.sc/Fiji), an open-source image analysis platform in combination with a set of functions in R (http://www.r-project.org/), an open-source program for statistical analysis. SAMA enables a rapid, exhaustive and quantitative 3D analysis of the shape of a population of structures in a 3D image. SAMA is cross-platform, licensed under the GPLv3 and available at http://montevil.theobio.org/content/sama. PMID:27035711

  12. A spherical harmonics intensity model for 3D segmentation and 3D shape analysis of heterochromatin foci.

    PubMed

    Eck, Simon; Wörz, Stefan; Müller-Ott, Katharina; Hahn, Matthias; Biesdorf, Andreas; Schotta, Gunnar; Rippe, Karsten; Rohr, Karl

    2016-08-01

    The genome is partitioned into regions of euchromatin and heterochromatin. The organization of heterochromatin is important for the regulation of cellular processes such as chromosome segregation and gene silencing, and their misregulation is linked to cancer and other diseases. We present a model-based approach for automatic 3D segmentation and 3D shape analysis of heterochromatin foci from 3D confocal light microscopy images. Our approach employs a novel 3D intensity model based on spherical harmonics, which analytically describes the shape and intensities of the foci. The model parameters are determined by fitting the model to the image intensities using least-squares minimization. To characterize the 3D shape of the foci, we exploit the computed spherical harmonics coefficients and determine a shape descriptor. We applied our approach to 3D synthetic image data as well as real 3D static and real 3D time-lapse microscopy images, and compared the performance with that of previous approaches. It turned out that our approach yields accurate 3D segmentation results and performs better than previous approaches. We also show that our approach can be used for quantifying 3D shape differences of heterochromatin foci.

  13. 3D Regression Heat Map Analysis of Population Study Data.

    PubMed

    Klemm, Paul; Lawonn, Kai; Glaßer, Sylvia; Niemann, Uli; Hegenscheid, Katrin; Völzke, Henry; Preim, Bernhard

    2016-01-01

    Epidemiological studies comprise heterogeneous data about a subject group to define disease-specific risk factors. These data contain information (features) about a subject's lifestyle, medical status as well as medical image data. Statistical regression analysis is used to evaluate these features and to identify feature combinations indicating a disease (the target feature). We propose an analysis approach of epidemiological data sets by incorporating all features in an exhaustive regression-based analysis. This approach combines all independent features w.r.t. a target feature. It provides a visualization that reveals insights into the data by highlighting relationships. The 3D Regression Heat Map, a novel 3D visual encoding, acts as an overview of the whole data set. It shows all combinations of two to three independent features with a specific target disease. Slicing through the 3D Regression Heat Map allows for the detailed analysis of the underlying relationships. Expert knowledge about disease-specific hypotheses can be included into the analysis by adjusting the regression model formulas. Furthermore, the influences of features can be assessed using a difference view comparing different calculation results. We applied our 3D Regression Heat Map method to a hepatic steatosis data set to reproduce results from a data mining-driven analysis. A qualitative analysis was conducted on a breast density data set. We were able to derive new hypotheses about relations between breast density and breast lesions with breast cancer. With the 3D Regression Heat Map, we present a visual overview of epidemiological data that allows for the first time an interactive regression-based analysis of large feature sets with respect to a disease. PMID:26529689

  14. 3D Regression Heat Map Analysis of Population Study Data.

    PubMed

    Klemm, Paul; Lawonn, Kai; Glaßer, Sylvia; Niemann, Uli; Hegenscheid, Katrin; Völzke, Henry; Preim, Bernhard

    2016-01-01

    Epidemiological studies comprise heterogeneous data about a subject group to define disease-specific risk factors. These data contain information (features) about a subject's lifestyle, medical status as well as medical image data. Statistical regression analysis is used to evaluate these features and to identify feature combinations indicating a disease (the target feature). We propose an analysis approach of epidemiological data sets by incorporating all features in an exhaustive regression-based analysis. This approach combines all independent features w.r.t. a target feature. It provides a visualization that reveals insights into the data by highlighting relationships. The 3D Regression Heat Map, a novel 3D visual encoding, acts as an overview of the whole data set. It shows all combinations of two to three independent features with a specific target disease. Slicing through the 3D Regression Heat Map allows for the detailed analysis of the underlying relationships. Expert knowledge about disease-specific hypotheses can be included into the analysis by adjusting the regression model formulas. Furthermore, the influences of features can be assessed using a difference view comparing different calculation results. We applied our 3D Regression Heat Map method to a hepatic steatosis data set to reproduce results from a data mining-driven analysis. A qualitative analysis was conducted on a breast density data set. We were able to derive new hypotheses about relations between breast density and breast lesions with breast cancer. With the 3D Regression Heat Map, we present a visual overview of epidemiological data that allows for the first time an interactive regression-based analysis of large feature sets with respect to a disease.

  15. 3D Network Analysis for Indoor Space Applications

    NASA Astrophysics Data System (ADS)

    Tsiliakou, E.; Dimopoulou, E.

    2016-10-01

    Indoor space differs from outdoor environments, since it is characterized by a higher level of structural complexity, geometry, as well as topological relations. Indoor space can be considered as the most important component in a building's conceptual modelling, on which applications such as indoor navigation, routing or analysis are performed. Therefore, the conceptual meaning of sub spaces or the activities taking place in physical building boundaries (e.g. walls), require the comprehension of the building's indoor hierarchical structure. The scope of this paper is to perform 3D network analysis in a building's interior and is structured as follows: In Section 1 the definition of indoor space is provided and indoor navigation requirements are analysed. Section 2 describes the processes of indoor space modeling, as well as routing applications. In Section 3, a case study is examined involving a 3D building model generated in CityEngine (exterior shell) and ArcScene (interior parts), in which the use of commercially available software tools (ArcGIS, ESRI), in terms of indoor routing and 3D network analysis, are explored. The fundamentals of performing 3D analysis with the ArcGIS Network Analyst extension were tested. Finally a geoprocessing model was presented, which was specifically designed to be used to interactively find the best route in ArcScene. The paper ends with discussion and concluding remarks on Section 4.

  16. Discovery of potent and selective urea-based ROCK inhibitors: Exploring the inhibitor's potency and ROCK2/PKA selectivity by 3D-QSAR, molecular docking and molecular dynamics simulations.

    PubMed

    Mei, Ding; Yin, Yan; Wu, Fanhong; Cui, Jiaxing; Zhou, Hong; Sun, Guofeng; Jiang, Yu; Feng, Yangbo

    2015-05-15

    An activity model and a selectivity model from 3D-QSAR studies were established by CoMFA and CoMSIA to explore the SAR. Then docking was used to study the binding modes between ligand and kinases (ROCK2 and PKA), and the molecular docking results were further validated by MD simulations. Computational results suggested that substitution containing positive charge attached to the middle phenyl ring, or electropositive group in urea linker was favored for both activity and ROCK2/PKA selectivity. Finally, three compounds were designed, and biological evaluation demonstrated that these molecular models were effective for guiding the design of potent and selective ROCK inhibitors.

  17. 3-D Experimental Fracture Analysis at High Temperature

    SciTech Connect

    John H. Jackson; Albert S. Kobayashi

    2001-09-14

    T*e, which is an elastic-plastic fracture parameter based on incremental theory of plasticity, was determined numerically and experimentally. The T*e integral of a tunneling crack in 2024-T3 aluminum, three point bend specimen was obtained through a hybrid analysis of moire interferometry and 3-D elastic-plastic finite element analysis. The results were verified by the good agreement between the experimentally and numerically determined T*e on the specimen surface.

  18. Comparative QSAR- and fragments distribution analysis of drugs, druglikes, metabolic substances, and antimicrobial compounds.

    PubMed

    Karakoc, Emre; Sahinalp, S Cenk; Cherkasov, Artem

    2006-01-01

    A number of binary QSAR models have been developed using methods of artificial neural networks, k-nearest neighbors, linear discriminative analysis, and multiple linear regression and have been compared for their ability to recognize five types of chemical compounds that include conventional drugs, inactive druglikes, antimicrobial substituents, and bacterial and human metabolites. Thus, 20 binary classifiers have been created using a variety of 'inductive' and traditional 2D QSAR descriptors which allowed up to 99% accurate separation of the studied groups of activities. The comparison of the performance by four computational approaches demonstrated that the neural nets result in generally more accurate predictions, followed closely by k-nearest neighbors methods. It has also been demonstrated that complementation of 'inductive' descriptors with conventional QSAR parameters does not generally improve the quality of resulting solutions, conforming high predictive ability of 'inductive' variables. The conducted comparative QSAR analysis based on a novel linear optimization approach has helped to identify the extent of overlapping between the studied groups of compounds, such as cross-recognition of bacterial metabolites and antimicrobial compounds reflecting their immanent resemblance and similar origin. Human metabolites have been characterized as a very distinctive class of substances, separated from all other groups in the descriptors space and exhibiting different QSAR behavior. The analysis of unique structural fragments and substituents revealed inhomogeneous scale-free organization of human metabolites illustrating the fact that certain molecular scaffolds (such as sugars and nucleotides) may be strongly favored by natural evolution. The established scale-free organization of human metabolites has been contemplated as a factor of their unique positioning in the descriptors space and their distinctive QSAR properties. It is anticipated that the study may bring

  19. A 3D image analysis tool for SPECT imaging

    NASA Astrophysics Data System (ADS)

    Kontos, Despina; Wang, Qiang; Megalooikonomou, Vasileios; Maurer, Alan H.; Knight, Linda C.; Kantor, Steve; Fisher, Robert S.; Simonian, Hrair P.; Parkman, Henry P.

    2005-04-01

    We have developed semi-automated and fully-automated tools for the analysis of 3D single-photon emission computed tomography (SPECT) images. The focus is on the efficient boundary delineation of complex 3D structures that enables accurate measurement of their structural and physiologic properties. We employ intensity based thresholding algorithms for interactive and semi-automated analysis. We also explore fuzzy-connectedness concepts for fully automating the segmentation process. We apply the proposed tools to SPECT image data capturing variation of gastric accommodation and emptying. These image analysis tools were developed within the framework of a noninvasive scintigraphic test to measure simultaneously both gastric emptying and gastric volume after ingestion of a solid or a liquid meal. The clinical focus of the particular analysis was to probe associations between gastric accommodation/emptying and functional dyspepsia. Employing the proposed tools, we outline effectively the complex three dimensional gastric boundaries shown in the 3D SPECT images. We also perform accurate volume calculations in order to quantitatively assess the gastric mass variation. This analysis was performed both with the semi-automated and fully-automated tools. The results were validated against manual segmentation performed by a human expert. We believe that the development of an automated segmentation tool for SPECT imaging of the gastric volume variability will allow for other new applications of SPECT imaging where there is a need to evaluate complex organ function or tumor masses.

  20. Development of a credible 3D-QSAR CoMSIA model and docking studies for a series of triazoles and tetrazoles containing 11β-HSD1 inhibitors.

    PubMed

    Murumkar, P R; Shinde, A C; Sharma, M K; Yamaguchi, H; Miniyar, P B; Yadav, M R

    2016-04-01

    Type 2 diabetes mellitus is described by insulin resistance and high fasting blood glucose. Increased levels of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme result in insulin resistance and metabolic syndrome. Inhibition of 11β-HSD1 decreases glucose production and increases hepatic insulin sensitivity. Use of selective 11β-HSD1 inhibitors could prove to be an effective strategy for the treatment of the disease. It was decided to identify the essential structural features required by any compound to possess 11β-HSD1 inhibitory activity. A dataset of 139 triazoles and tetrazoles having 11β-HSD1 inhibitory activity was used for the development of a 3D-QSAR model. The best comparative molecular field analysis (CoMFA) model was generated with databased alignment, which was further used for comparative molecular similarity indices analysis (CoMSIA). The optimal CoMSIA model showed [Formula: see text] = 0.809 with five components, [Formula: see text] = 0.931, SEE = 0.323 and F-value = 249.126. The CoMSIA model offered better prediction than the CoMFA model with [Formula: see text] = 0.522 and 0.439, respectively, indicating that the CoMSIA model appeared to be a better one for the prediction of activity for the newly designed 11β-HSD1 inhibitors. The selectivity aspect of 11β-HSD1 over 11β-HSD2 was studied with the help of docking studies. PMID:27094303

  1. 3D Guided Wave Motion Analysis on Laminated Composites

    NASA Technical Reports Server (NTRS)

    Tian, Zhenhua; Leckey, Cara; Yu, Lingyu

    2013-01-01

    Ultrasonic guided waves have proved useful for structural health monitoring (SHM) and nondestructive evaluation (NDE) due to their ability to propagate long distances with less energy loss compared to bulk waves and due to their sensitivity to small defects in the structure. Analysis of actively transmitted ultrasonic signals has long been used to detect and assess damage. However, there remain many challenging tasks for guided wave based SHM due to the complexity involved with propagating guided waves, especially in the case of composite materials. The multimodal nature of the ultrasonic guided waves complicates the related damage analysis. This paper presents results from parallel 3D elastodynamic finite integration technique (EFIT) simulations used to acquire 3D wave motion in the subject laminated carbon fiber reinforced polymer composites. The acquired 3D wave motion is then analyzed by frequency-wavenumber analysis to study the wave propagation and interaction in the composite laminate. The frequency-wavenumber analysis enables the study of individual modes and visualization of mode conversion. Delamination damage has been incorporated into the EFIT model to generate "damaged" data. The potential for damage detection in laminated composites is discussed in the end.

  2. Visualization and Analysis of 3D Gene Expression Data

    SciTech Connect

    Bethel, E. Wes; Rubel, Oliver; Weber, Gunther H.; Hamann, Bernd; Hagen, Hans

    2007-10-25

    Recent methods for extracting precise measurements ofspatial gene expression patterns from three-dimensional (3D) image dataopens the way for new analysis of the complex gene regulatory networkscontrolling animal development. To support analysis of this novel andhighly complex data we developed PointCloudXplore (PCX), an integratedvisualization framework that supports dedicated multi-modal, physical andinformation visualization views along with algorithms to aid in analyzingthe relationships between gene expression levels. Using PCX, we helpedour science stakeholders to address many questions in 3D gene expressionresearch, e.g., to objectively define spatial pattern boundaries andtemporal profiles of genes and to analyze how mRNA patterns arecontrolled by their regulatory transcription factors.

  3. Advanced computational tools for 3-D seismic analysis

    SciTech Connect

    Barhen, J.; Glover, C.W.; Protopopescu, V.A.

    1996-06-01

    The global objective of this effort is to develop advanced computational tools for 3-D seismic analysis, and test the products using a model dataset developed under the joint aegis of the United States` Society of Exploration Geophysicists (SEG) and the European Association of Exploration Geophysicists (EAEG). The goal is to enhance the value to the oil industry of the SEG/EAEG modeling project, carried out with US Department of Energy (DOE) funding in FY` 93-95. The primary objective of the ORNL Center for Engineering Systems Advanced Research (CESAR) is to spearhead the computational innovations techniques that would enable a revolutionary advance in 3-D seismic analysis. The CESAR effort is carried out in collaboration with world-class domain experts from leading universities, and in close coordination with other national laboratories and oil industry partners.

  4. Advancements in 3D Structural Analysis of Geothermal Systems

    SciTech Connect

    Siler, Drew L; Faulds, James E; Mayhew, Brett; McNamara, David

    2013-06-23

    Robust geothermal activity in the Great Basin, USA is a product of both anomalously high regional heat flow and active fault-controlled extension. Elevated permeability associated with some fault systems provides pathways for circulation of geothermal fluids. Constraining the local-scale 3D geometry of these structures and their roles as fluid flow conduits is crucial in order to mitigate both the costs and risks of geothermal exploration and to identify blind (no surface expression) geothermal resources. Ongoing studies have indicated that much of the robust geothermal activity in the Great Basin is associated with high density faulting at structurally complex fault intersection/interaction areas, such as accommodation/transfer zones between discrete fault systems, step-overs or relay ramps in fault systems, intersection zones between faults with different strikes or different senses of slip, and horse-tailing fault terminations. These conceptualized models are crucial for locating and characterizing geothermal systems in a regional context. At the local scale, however, pinpointing drilling targets and characterizing resource potential within known or probable geothermal areas requires precise 3D characterization of the system. Employing a variety of surface and subsurface data sets, we have conducted detailed 3D geologic analyses of two Great Basin geothermal systems. Using EarthVision (Dynamic Graphics Inc., Alameda, CA) we constructed 3D geologic models of both the actively producing Brady’s geothermal system and a ‘greenfield’ geothermal prospect at Astor Pass, NV. These 3D models allow spatial comparison of disparate data sets in 3D and are the basis for quantitative structural analyses that can aid geothermal resource assessment and be used to pinpoint discrete drilling targets. The relatively abundant data set at Brady’s, ~80 km NE of Reno, NV, includes 24 wells with lithologies interpreted from careful analysis of cuttings and core, a 1

  5. Combined 3D-QSAR, molecular docking, molecular dynamics simulation, and binding free energy calculation studies on the 5-hydroxy-2H-pyridazin-3-one derivatives as HCV NS5B polymerase inhibitors.

    PubMed

    Yu, Haijing; Fang, Yu; Lu, Xia; Liu, Yongjuan; Zhang, Huabei

    2014-01-01

    The NS5B RNA-dependent RNA polymerase (RdRP) is a promising therapeutic target for developing novel anti-hepatitis C virus (HCV) drugs. In this work, a combined molecular modeling study was performed on a series of 193 5-hydroxy-2H-pyridazin-3-one derivatives as inhibitors of HCV NS5B Polymerase. The best 3D-QSAR models, including CoMFA and CoMSIA, are based on receptor (or docking). Furthermore, a 40-ns molecular dynamics (MD) simulation and binding free energy calculations using docked structures of NS5B with ten compounds, which have diverse structures and pIC50 values, were employed to determine the detailed binding process and to compare the binding modes of the inhibitors with different activities. On one side, the stability and rationality of molecular docking and 3D-QSAR results were validated by MD simulation. The binding free energies calculated by the MM-PBSA method gave a good correlation with the experimental biological activity. On the other side, by analyzing some differences between the molecular docking and the MD simulation results, we can find that the MD simulation could also remedy the defects of molecular docking. The analyses of the combined molecular modeling results have identified that Tyr448, Ser556, and Asp318 are the key amino acid residues in the NS5B binding pocket. The results from this study can provide some insights into the development of novel potent NS5B inhibitors.

  6. Beam Optics Analysis - An Advanced 3D Trajectory Code

    SciTech Connect

    Ives, R. Lawrence; Bui, Thuc; Vogler, William; Neilson, Jeff; Read, Mike; Shephard, Mark; Bauer, Andrew; Datta, Dibyendu; Beal, Mark

    2006-01-03

    Calabazas Creek Research, Inc. has completed initial development of an advanced, 3D program for modeling electron trajectories in electromagnetic fields. The code is being used to design complex guns and collectors. Beam Optics Analysis (BOA) is a fully relativistic, charged particle code using adaptive, finite element meshing. Geometrical input is imported from CAD programs generating ACIS-formatted files. Parametric data is inputted using an intuitive, graphical user interface (GUI), which also provides control of convergence, accuracy, and post processing. The program includes a magnetic field solver, and magnetic information can be imported from Maxwell 2D/3D and other programs. The program supports thermionic emission and injected beams. Secondary electron emission is also supported, including multiple generations. Work on field emission is in progress as well as implementation of computer optimization of both the geometry and operating parameters. The principle features of the program and its capabilities are presented.

  7. Beam Optics Analysis — An Advanced 3D Trajectory Code

    NASA Astrophysics Data System (ADS)

    Ives, R. Lawrence; Bui, Thuc; Vogler, William; Neilson, Jeff; Read, Mike; Shephard, Mark; Bauer, Andrew; Datta, Dibyendu; Beal, Mark

    2006-01-01

    Calabazas Creek Research, Inc. has completed initial development of an advanced, 3D program for modeling electron trajectories in electromagnetic fields. The code is being used to design complex guns and collectors. Beam Optics Analysis (BOA) is a fully relativistic, charged particle code using adaptive, finite element meshing. Geometrical input is imported from CAD programs generating ACIS-formatted files. Parametric data is inputted using an intuitive, graphical user interface (GUI), which also provides control of convergence, accuracy, and post processing. The program includes a magnetic field solver, and magnetic information can be imported from Maxwell 2D/3D and other programs. The program supports thermionic emission and injected beams. Secondary electron emission is also supported, including multiple generations. Work on field emission is in progress as well as implementation of computer optimization of both the geometry and operating parameters. The principle features of the program and its capabilities are presented.

  8. Uncertainty Analysis for RELAP5-3D

    SciTech Connect

    Aaron J. Pawel; Dr. George L. Mesina

    2011-08-01

    In its current state, RELAP5-3D is a 'best-estimate' code; it is one of our most reliable programs for modeling what occurs within reactor systems in transients from given initial conditions. This code, however, remains an estimator. A statistical analysis has been performed that begins to lay the foundation for a full uncertainty analysis. By varying the inputs over assumed probability density functions, the output parameters were shown to vary. Using such statistical tools as means, variances, and tolerance intervals, a picture of how uncertain the results are based on the uncertainty of the inputs has been obtained.

  9. Breast tumor angiogenesis analysis using 3D power Doppler ultrasound

    NASA Astrophysics Data System (ADS)

    Chang, Ruey-Feng; Huang, Sheng-Fang; Lee, Yu-Hau; Chen, Dar-Ren; Moon, Woo Kyung

    2006-03-01

    Angiogenesis is the process that correlates to tumor growth, invasion, and metastasis. Breast cancer angiogenesis has been the most extensively studied and now serves as a paradigm for understanding the biology of angiogenesis and its effects on tumor outcome and patient prognosis. Most studies on characterization of angiogenesis focus on pixel/voxel counts more than morphological analysis. Nevertheless, in cancer, the blood flow is greatly affected by the morphological changes, such as the number of vessels, branching pattern, length, and diameter. This paper presents a computer-aided diagnostic (CAD) system that can quantify vascular morphology using 3-D power Doppler ultrasound (US) on breast tumors. We propose a scheme to extract the morphological information from angiography and to relate them to tumor diagnosis outcome. At first, a 3-D thinning algorithm helps narrow down the vessels into their skeletons. The measurements of vascular morphology significantly rely on the traversing of the vascular trees produced from skeletons. Our study of 3-D assessment of vascular morphological features regards vessel count, length, bifurcation, and diameter of vessels. Investigations into 221 solid breast tumors including 110 benign and 111 malignant cases, the p values using the Student's t-test for all features are less than 0.05 indicating that the proposed features are deemed statistically significant. Our scheme focuses on the vascular architecture without involving the technique of tumor segmentation. The results show that the proposed method is feasible, and have a good agreement with the diagnosis of the pathologists.

  10. USM3D Analysis of Low Boom Configuration

    NASA Technical Reports Server (NTRS)

    Carter, Melissa B.; Campbell, Richard L.; Nayani, Sudheer N.

    2011-01-01

    In the past few years considerable improvement was made in NASA's in house boom prediction capability. As part of this improved capability, the USM3D Navier-Stokes flow solver, when combined with a suitable unstructured grid, went from accurately predicting boom signatures at 1 body length to 10 body lengths. Since that time, the research emphasis has shifted from analysis to the design of supersonic configurations with boom signature mitigation In order to design an aircraft, the techniques for accurately predicting boom and drag need to be determined. This paper compares CFD results with the wind tunnel experimental results conducted on a Gulfstream reduced boom and drag configuration. Two different wind-tunnel models were designed and tested for drag and boom data. The goal of this study was to assess USM3D capability for predicting both boom and drag characteristics. Overall, USM3D coupled with a grid that was sheared and stretched was able to reasonably predict boom signature. The computational drag polar matched the experimental results for a lift coefficient above 0.1 despite some mismatch in the predicted lift-curve slope.

  11. The 3D inelastic analysis methods for hot section components

    NASA Technical Reports Server (NTRS)

    Mcknight, R. L.; Maffeo, R. J.; Tipton, M. T.; Weber, G.

    1992-01-01

    A two-year program to develop advanced 3D inelastic structural stress analysis methods and solution strategies for more accurate and cost effective analysis of combustors, turbine blades, and vanes is described. The approach was to develop a matrix of formulation elements and constitutive models. Three constitutive models were developed in conjunction with optimized iterating techniques, accelerators, and convergence criteria within a framework of dynamic time incrementing. Three formulation models were developed: an eight-noded midsurface shell element; a nine-noded midsurface shell element; and a twenty-noded isoparametric solid element. A separate computer program has been developed for each combination of constitutive model-formulation model. Each program provides a functional stand alone capability for performing cyclic nonlinear structural analysis. In addition, the analysis capabilities incorporated into each program can be abstracted in subroutine form for incorporation into other codes or to form new combinations.

  12. On 3D inelastic analysis methods for hot section components

    NASA Technical Reports Server (NTRS)

    Mcknight, R. L.; Chen, P. C.; Dame, L. T.; Holt, R. V.; Huang, H.; Hartle, M.; Gellin, S.; Allen, D. H.; Haisler, W. E.

    1986-01-01

    Accomplishments are described for the 2-year program, to develop advanced 3-D inelastic structural stress analysis methods and solution strategies for more accurate and cost effective analysis of combustors, turbine blades and vanes. The approach was to develop a matrix of formulation elements and constitutive models. Three constitutive models were developed in conjunction with optimized iterating techniques, accelerators, and convergence criteria within a framework of dynamic time incrementing. Three formulations models were developed; an eight-noded mid-surface shell element, a nine-noded mid-surface shell element and a twenty-noded isoparametric solid element. A separate computer program was developed for each combination of constitutive model-formulation model. Each program provides a functional stand alone capability for performing cyclic nonlinear structural analysis. In addition, the analysis capabilities incorporated into each program can be abstracted in subroutine form for incorporation into other codes or to form new combinations.

  13. The development of a 3D risk analysis method.

    PubMed

    I, Yet-Pole; Cheng, Te-Lung

    2008-05-01

    Much attention has been paid to the quantitative risk analysis (QRA) research in recent years due to more and more severe disasters that have happened in the process industries. Owing to its calculation complexity, very few software, such as SAFETI, can really make the risk presentation meet the practice requirements. However, the traditional risk presentation method, like the individual risk contour in SAFETI, is mainly based on the consequence analysis results of dispersion modeling, which usually assumes that the vapor cloud disperses over a constant ground roughness on a flat terrain with no obstructions and concentration fluctuations, which is quite different from the real situations of a chemical process plant. All these models usually over-predict the hazardous regions in order to maintain their conservativeness, which also increases the uncertainty of the simulation results. On the other hand, a more rigorous model such as the computational fluid dynamics (CFD) model can resolve the previous limitations; however, it cannot resolve the complexity of risk calculations. In this research, a conceptual three-dimensional (3D) risk calculation method was proposed via the combination of results of a series of CFD simulations with some post-processing procedures to obtain the 3D individual risk iso-surfaces. It is believed that such technique will not only be limited to risk analysis at ground level, but also be extended into aerial, submarine, or space risk analyses in the near future.

  14. Uncertainty Analysis of RELAP5-3D

    SciTech Connect

    Alexandra E Gertman; Dr. George L Mesina

    2012-07-01

    As world-wide energy consumption continues to increase, so does the demand for the use of alternative energy sources, such as Nuclear Energy. Nuclear Power Plants currently supply over 370 gigawatts of electricity, and more than 60 new nuclear reactors have been commissioned by 15 different countries. The primary concern for Nuclear Power Plant operation and lisencing has been safety. The safety of the operation of Nuclear Power Plants is no simple matter- it involves the training of operators, design of the reactor, as well as equipment and design upgrades throughout the lifetime of the reactor, etc. To safely design, operate, and understand nuclear power plants, industry and government alike have relied upon the use of best-estimate simulation codes, which allow for an accurate model of any given plant to be created with well-defined margins of safety. The most widely used of these best-estimate simulation codes in the Nuclear Power industry is RELAP5-3D. Our project focused on improving the modeling capabilities of RELAP5-3D by developing uncertainty estimates for its calculations. This work involved analyzing high, medium, and low ranked phenomena from an INL PIRT on a small break Loss-Of-Coolant Accident as wall as an analysis of a large break Loss-Of- Coolant Accident. Statistical analyses were performed using correlation coefficients. To perform the studies, computer programs were written that modify a template RELAP5 input deck to produce one deck for each combination of key input parameters. Python scripting enabled the running of the generated input files with RELAP5-3D on INL’s massively parallel cluster system. Data from the studies was collected and analyzed with SAS. A summary of the results of our studies are presented.

  15. A combined CoMFA and CoMSIA 3D-QSAR study of benzamide type antibacterial inhibitors of the FtsZ protein in drug-resistant Staphylococcus aureus.

    PubMed

    Andrades, J; Campanini, J; Vásquez, D; Silvestri, C; Morales, C; Romero, J; Mella, J

    2015-01-01

    A major problem today is bacterial resistance to antibiotics and the small number of new therapeutic agents approved in recent years. The development of new antibiotics capable of acting on new targets is urgently required. The filamenting temperature-sensitive Z (FtsZ) bacterial protein is a key biomolecule for bacterial division and survival. This makes FtsZ an attractive new pharmacological target for the development of antibacterial agents. There have been several attempts to develop ligands able to inhibit FtsZ. Despite the large number of synthesized compounds that inhibit the FtsZ protein, there are no quantitative structure-activity relationships (QSAR) that allow for the rational design and synthesis of promising new molecules. We present the first 3D-QSAR study of a large and diverse set of molecules that are able to inhibit the FtsZ bacterial protein. We summarize a set of chemical changes that can be made in the steric, electrostatic, hydrophobic and donor/acceptor hydrogen-bonding properties of the pharmacophore, to generate new bioactive molecules against FtsZ. These results provide a rational guide for the design and synthesis of promising new antibacterial agents, supported by the strong statistical parameters obtained from CoMFA (r(2)(pred) = 0.974) and CoMSIA (r(2)(pred) = 0.980) analyses. PMID:26505124

  16. The 3D inelastic analysis methods for hot section components

    NASA Technical Reports Server (NTRS)

    Dame, L. T.; Mcknight, R. L.

    1983-01-01

    The objective of this research is to develop an analytical tool capable of economically evaluating the cyclic time dependent plasticity which occurs in hot section engine components in areas of strain concentration resulting from the combination of both mechanical and thermal stresses. The techniques developed must be capable of accommodating large excursions in temperatures with the associated variations in material properties including plasticity and creep. The overall objective of this proposed program is to develop advanced 3-D inelastic structural/stress analysis methods and solution strategies for more accurate and yet more cost effective analysis of combustors, turbine blades, and vanes. The approach will be to develop four different theories, one linear and three higher order with increasing complexities including embedded singularities.

  17. QSAR analysis of antitumor activities of 3,4-ethylenedioxythiphene derivatives

    NASA Astrophysics Data System (ADS)

    Rastija, Vesna; Bajić, Miroslav; Stolić, Ivana; Krstulović, Luka; Jukić, Marijana; Glavaš-Obrovac, Ljubica

    2015-12-01

    QSAR analysis was performed for the antitumor activity of 27 derivatives of 3,4-ethylenedioxythiophene against six carcinoma cell lines. The best models were obtained with surface area (SAG) in combination with lipohilicity (log P) as descriptors. Results have shown that molecules with smaller solvent accessible surface area and higher lipophilicy should have higher biological activity against carcinoma cell.

  18. Dynamical Systems Analysis of Fully 3D Ocean Features

    NASA Astrophysics Data System (ADS)

    Pratt, L. J.

    2011-12-01

    Dynamical systems analysis of transport and stirring processes has been developed most thoroughly for 2D flow fields. The calculation of manifolds, turnstile lobes, transport barriers, etc. based on observations of the ocean is most often conducted near the sea surface, whereas analyses at depth, usually carried out with model output, is normally confined to constant-z surfaces. At the meoscale and larger, ocean flows are quasi 2D, but smaller scale (submesoscale) motions, including mixed layer phenomena with significant vertical velocity, may be predominantly 3D. The zoology of hyperbolic trajectories becomes richer in such cases and their attendant manifolds are much more difficult to calculate. I will describe some of the basic geometrical features and corresponding Lagrangian Coherent Features expected to arise in upper ocean fronts, eddies, and Langmuir circulations. Traditional GFD models such as the rotating can flow may capture the important generic features. The dynamical systems approach is most helpful when these features are coherent and persistent and the implications and difficulties for this requirement in fully 3D flows will also be discussed.

  19. 3D-Geomorphometrics tooth shape analysis in hypodontia

    PubMed Central

    Al-Shahrani, Ibrahim; Dirks, Wendy; Jepson, Nicholas; Khalaf, Khaled

    2014-01-01

    Assessment of tooth morphology is an important part of the diagnosis and management of hypodontia patients. Several techniques have been used to analyze tooth form in hypodontia patients and these have shown smaller tooth dimensions and anomalous tooth shapes in patients with hypodontia when compared with controls. However, previous studies have mainly used 2D images and provided limited information. In the present study, 3D surface-imaging and statistical shape analysis were used to evaluate tooth form differences between hypodontia and control patients. Eighteen anatomical landmarks were recorded on the clinical crown of the lower left first permanent molar of 3D scanned study models of hypodontia and control subjects. The study sample group comprised of 120 hypodontia patients (40 mild, 40 moderate, and 40 severe hypodontia patients) and 40 age- and sex-matched controls. Procrustes coordinates were utilized to scale and superimpose the landmark coordinate data and then were subjected to principal component analysis (PCA). Subsequently, differences in shape as well as size were tested statistically using allometric analysis and MANOVA. Significant interaction was found between the two factor variables “group” and “sex” (p < 0.002). Overall expected accuracies were 66 and 56% for females and males, respectively, in the cross-validated discriminant-analysis using the first 20 PCs. Hypodontia groups showed significant shape differences compared with the control subjects (p < 0.0001). Significant differences in tooth crown shape were also found between sexes (p < 0.0001) within groups. Furthermore, the degree of variation in tooth form was proportional to the degree of the severity of the hypodontia. Thus, quantitative measurement of tooth shape in hypodontia patients may enhance the multidisciplinary management of those patients. PMID:24795649

  20. Comparative visual analysis of 3D urban wind simulations

    NASA Astrophysics Data System (ADS)

    Röber, Niklas; Salim, Mohamed; Grawe, David; Leitl, Bernd; Böttinger, Michael; Schlünzen, Heinke

    2016-04-01

    Climate simulations are conducted in large quantity for a variety of different applications. Many of these simulations focus on global developments and study the Earth's climate system using a coupled atmosphere ocean model. Other simulations are performed on much smaller regional scales, to study very small fine grained climatic effects. These microscale climate simulations pose similar, yet also different, challenges for the visualization and the analysis of the simulation data. Modern interactive visualization and data analysis techniques are very powerful tools to assist the researcher in answering and communicating complex research questions. This presentation discusses comparative visualization for several different wind simulations, which were created using the microscale climate model MITRAS. The simulations differ in wind direction and speed, but are all centered on the same simulation domain: An area of Hamburg-Wilhelmsburg that hosted the IGA/IBA exhibition in 2013. The experiments contain a scenario case to analyze the effects of single buildings, as well as examine the impact of the Coriolis force within the simulation. The scenario case is additionally compared with real measurements from a wind tunnel experiment to ascertain the accuracy of the simulation and the model itself. We also compare different approaches for tree modeling and evaluate the stability of the model. In this presentation, we describe not only our workflow to efficiently and effectively visualize microscale climate simulation data using common 3D visualization and data analysis techniques, but also discuss how to compare variations of a simulation and how to highlight the subtle differences in between them. For the visualizations we use a range of different 3D tools that feature techniques for statistical data analysis, data selection, as well as linking and brushing.

  1. QSAR modeling for quinoxaline derivatives using genetic algorithm and simulated annealing based feature selection.

    PubMed

    Ghosh, P; Bagchi, M C

    2009-01-01

    With a view to the rational design of selective quinoxaline derivatives, 2D and 3D-QSAR models have been developed for the prediction of anti-tubercular activities. Successful implementation of a predictive QSAR model largely depends on the selection of a preferred set of molecular descriptors that can signify the chemico-biological interaction. Genetic algorithm (GA) and simulated annealing (SA) are applied as variable selection methods for model development. 2D-QSAR modeling using GA or SA based partial least squares (GA-PLS and SA-PLS) methods identified some important topological and electrostatic descriptors as important factor for tubercular activity. Kohonen network and counter propagation artificial neural network (CP-ANN) considering GA and SA based feature selection methods have been applied for such QSAR modeling of Quinoxaline compounds. Out of a variable pool of 380 molecular descriptors, predictive QSAR models are developed for the training set and validated on the test set compounds and a comparative study of the relative effectiveness of linear and non-linear approaches has been investigated. Further analysis using 3D-QSAR technique identifies two models obtained by GA-PLS and SA-PLS methods leading to anti-tubercular activity prediction. The influences of steric and electrostatic field effects generated by the contribution plots are discussed. The results indicate that SA is a very effective variable selection approach for such 3D-QSAR modeling.

  2. Colossal Tooling Design: 3D Simulation for Ergonomic Analysis

    NASA Technical Reports Server (NTRS)

    Hunter, Steve L.; Dischinger, Charles; Thomas, Robert E.; Babai, Majid

    2003-01-01

    The application of high-level 3D simulation software to the design phase of colossal mandrel tooling for composite aerospace fuel tanks was accomplished to discover and resolve safety and human engineering problems. The analyses were conducted to determine safety, ergonomic and human engineering aspects of the disassembly process of the fuel tank composite shell mandrel. Three-dimensional graphics high-level software, incorporating various ergonomic analysis algorithms, was utilized to determine if the process was within safety and health boundaries for the workers carrying out these tasks. In addition, the graphical software was extremely helpful in the identification of material handling equipment and devices for the mandrel tooling assembly/disassembly process.

  3. Structural analysis of tropical cyclone using INSAT-3D observations

    NASA Astrophysics Data System (ADS)

    Jaiswal, Neeru; Kishtawal, C. M.

    2016-05-01

    The continuous observations from visible and thermal infrared (TIR) channels of geostationary satellites are highly useful for obtaining the features associated with the shape and dynamics of cloud structures within the tropical cyclones (TCs). As TC develops from an unstructured cloud cluster and intensifies, the cloud structures become more axisymmetric around the centre of the TC. To better understand the structure of TC during different stages of its evolution i.e. from its cyclogenesis to maturity and dissipation, the continuous satellite observations plays a key role. The high spatial and temporal resolution observations from geostationary satellites are very useful in order to analyze the cloud organization during the cyclogenesis. The gradient of the brightness temperatures measures the level of symmetry of each structure, which characterizes the degree of cloud organization of the TC. In the present work, the structural analysis of TC during its life period using the observations from Indian geostationary satellite INSAT-3D has been discussed. The visible and TIR observations from INSAT-3D satellite were used to fix the center position of the cyclone which is an input for the cyclone track and intensity prediction models. This data is also used to estimate the intensity of cyclone in the advanced Dvorak technique (ADT), and in the estimation of radius of maximum winds (Rmax) of TC which is an essential input parameter for the prediction of storm surge associated to the cyclones. The different patterns of cloud structure during the intensification stage, eye-wall formation and dissipation have been discussed. The early identification of these features helps in predicting the rapid intensification of TC which in turn improves the intensity predictions.

  4. Analysis and dynamic 3D visualization of cerebral blood flow combining 3D and 4D MR image sequences

    NASA Astrophysics Data System (ADS)

    Forkert, Nils Daniel; Säring, Dennis; Fiehler, Jens; Illies, Till; Möller, Dietmar; Handels, Heinz

    2009-02-01

    In this paper we present a method for the dynamic visualization of cerebral blood flow. Spatio-temporal 4D magnetic resonance angiography (MRA) image datasets and 3D MRA datasets with high spatial resolution were acquired for the analysis of arteriovenous malformations (AVMs). One of the main tasks is the combination of the information of the 3D and 4D MRA image sequences. Initially, in the 3D MRA dataset the vessel system is segmented and a 3D surface model is generated. Then, temporal intensity curves are analyzed voxelwise in the 4D MRA image sequences. A curve fitting of the temporal intensity curves to a patient individual reference curve is used to extract the bolus arrival times in the 4D MRA sequences. After non-linear registration of both MRA datasets the extracted hemodynamic information is transferred to the surface model where the time points of inflow can be visualized color coded dynamically over time. The dynamic visualizations computed using the curve fitting method for the estimation of the bolus arrival times were rated superior compared to those computed using conventional approaches for bolus arrival time estimation. In summary the procedure suggested allows a dynamic visualization of the individual hemodynamic situation and better understanding during the visual evaluation of cerebral vascular diseases.

  5. 3D Finite Element Analysis of Particle-Reinforced Aluminum

    NASA Technical Reports Server (NTRS)

    Shen, H.; Lissenden, C. J.

    2002-01-01

    Deformation in particle-reinforced aluminum has been simulated using three distinct types of finite element model: a three-dimensional repeating unit cell, a three-dimensional multi-particle model, and two-dimensional multi-particle models. The repeating unit cell model represents a fictitious periodic cubic array of particles. The 3D multi-particle (3D-MP) model represents randomly placed and oriented particles. The 2D generalized plane strain multi-particle models were obtained from planar sections through the 3D-MP model. These models were used to study the tensile macroscopic stress-strain response and the associated stress and strain distributions in an elastoplastic matrix. The results indicate that the 2D model having a particle area fraction equal to the particle representative volume fraction of the 3D models predicted the same macroscopic stress-strain response as the 3D models. However, there are fluctuations in the particle area fraction in a representative volume element. As expected, predictions from 2D models having different particle area fractions do not agree with predictions from 3D models. More importantly, it was found that the microscopic stress and strain distributions from the 2D models do not agree with those from the 3D-MP model. Specifically, the plastic strain distribution predicted by the 2D model is banded along lines inclined at 45 deg from the loading axis while the 3D model prediction is not. Additionally, the triaxial stress and maximum principal stress distributions predicted by 2D and 3D models do not agree. Thus, it appears necessary to use a multi-particle 3D model to accurately predict material responses that depend on local effects, such as strain-to-failure, fracture toughness, and fatigue life.

  6. 3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer.

    PubMed

    Chaube, Udit; Chhatbar, Dhara; Bhatt, Hardik

    2016-02-01

    According to WHO statistics, lung cancer is one of the leading causes of death among all other types of cancer. Many genes get mutated in lung cancer but involvement of EGFR and KRAS are more common. Unavailability of drugs or resistance to the available drugs is the major problem in the treatment of lung cancer. In the present research, mTOR was selected as an alternative target for the treatment of lung cancer which involves PI3K/AKT/mTOR pathway. 28 synthetic mTOR inhibitors were selected from the literature. Ligand based approach (CoMFA and CoMSIA) and structure based approach (molecular dynamics simulations assisted molecular docking study) were applied for the identification of important features of benzoxazepine moiety, responsible for mTOR inhibition. Three different alignments were tried to obtain best QSAR model, of which, distil was found to be the best method, as it gave good statistical results. In CoMFA, Leave One Out (LOO) cross validated coefficients (q(2)), conventional coefficient (r(2)) and predicted correlation coefficient (r(2)pred) values were found to be 0.615, 0.990 and 0.930, respectively. Similarly in CoMSIA, q(2), r(2)ncv and r(2)pred values were found to be 0.748, 0.986 and 0.933, respectively. Molecular dynamics and simulations study revealed that B-chain of mTOR protein was stable at and above 500 FS with respect to temperature (at and above 298 K), Potential energy (at and above 7669.72 kJ/mol) and kinetic energy (at and above 4009.77 kJ/mol). Molecular docking study was performed on simulated protein of mTOR which helped to correlate interactions of amino acids surrounded to the ligand with contour maps generated by QSAR method. Important features of benzoxazepine were identified by contour maps and molecular docking study which would be useful to design novel molecules as mTOR inhibitors for the treatment of lung cancer.

  7. Understanding Crystal Populations; Looking Towards 3D Quantitative Analysis

    NASA Astrophysics Data System (ADS)

    Jerram, D. A.; Morgan, D. J.

    2010-12-01

    In order to understand volcanic systems, the potential record held within crystal populations needs to be revealed. It is becoming increasingly clear, however, that the crystal populations that arrive at the surface in volcanic eruptions are commonly mixtures of crystals, which may be representative of simple crystallization, recycling of crystals and incorporation of alien crystals. If we can quantify the true 3D population within a sample then we will be able to separate crystals with different histories and begin to interrogate the true and complex plumbing within the volcanic system. Modeling crystal populations is one area where we can investigate the best methodologies to use when dealing with sections through 3D populations. By producing known 3D shapes and sizes with virtual textures and looking at the statistics of shape and size when such populations are sectioned, we are able to gain confidence about what our 2D information is telling us about the population. We can also use this approach to test the size of population we need to analyze. 3D imaging through serial sectioning or x-ray CT, provides a complete 3D quantification of a rocks texture. Individual phases can be identified and in principle the true 3D statistics of the population can be interrogated. In practice we need to develop strategies (as with 2D-3D transformations), that enable a true characterization of the 3D data, and an understanding of the errors and pitfalls that exist. Ultimately, the reproduction of true 3D textures and the wealth of information they hold, is now within our reach.

  8. Design, biological evaluation and 3D QSAR studies of novel dioxin-containing pyrazoline derivatives with thiourea skeleton as selective HER-2 inhibitors

    NASA Astrophysics Data System (ADS)

    Yang, Bing; Yang, Yu-Shun; Yang, Na; Li, Guigen; Zhu, Hai-Liang

    2016-06-01

    A series of novel dioxin-containing pyrazoline derivatives with thiourea skeleton have been designed, synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. A majority of them displayed selective HER-2 inhibitory activity against EGFR inhibitory activity. Compound C20 displayed the most potent activity against HER-2 and MDA-MB-453 human breast cancer cell line (IC50 = 0.03 μM and GI50 = 0.15 μM), being slightly more potent than the positive control Erlotinib (IC50 = 0.16 μM and GI50 = 1.56 μM) and comparable with Lapatinib (IC50 = 0.01 μM and GI50 = 0.03 μM). It is a more exciting result that C20 was over 900 times more potent against HER-2 than against EGFR while this value was 0.19 for Erlotinib and 1.00 for Lapatinib, indicating high selectivity. The results of docking simulation indicate that the dioxin moiety occupied the exit of the active pocket and pushed the carbothioamide deep into the active site. QSAR models have been built with activity data and binding conformations to begin our work in this paper as well as to provide a reliable tool for reasonable design of EGFR/HER-2 inhibitors in future.

  9. Quantitative Analysis of Autophagy using Advanced 3D Fluorescence Microscopy

    PubMed Central

    Changou, Chun A.; Wolfson, Deanna L.; Ahluwalia, Balpreet Singh; Bold, Richard J.; Kung, Hsing-Jien; Chuang, Frank Y.S.

    2013-01-01

    Prostate cancer is the leading form of malignancies among men in the U.S. While surgery carries a significant risk of impotence and incontinence, traditional chemotherapeutic approaches have been largely unsuccessful. Hormone therapy is effective at early stage, but often fails with the eventual development of hormone-refractory tumors. We have been interested in developing therapeutics targeting specific metabolic deficiency of tumor cells. We recently showed that prostate tumor cells specifically lack an enzyme (argininosuccinate synthase, or ASS) involved in the synthesis of the amino acid arginine1. This condition causes the tumor cells to become dependent on exogenous arginine, and they undergo metabolic stress when free arginine is depleted by arginine deiminase (ADI)1,10. Indeed, we have shown that human prostate cancer cells CWR22Rv1 are effectively killed by ADI with caspase-independent apoptosis and aggressive autophagy (or macroautophagy)1,2,3. Autophagy is an evolutionarily-conserved process that allows cells to metabolize unwanted proteins by lysosomal breakdown during nutritional starvation4,5. Although the essential components of this pathway are well-characterized6,7,8,9, many aspects of the molecular mechanism are still unclear - in particular, what is the role of autophagy in the death-response of prostate cancer cells after ADI treatment? In order to address this question, we required an experimental method to measure the level and extent of autophagic response in cells - and since there are no known molecular markers that can accurately track this process, we chose to develop an imaging-based approach, using quantitative 3D fluorescence microscopy11,12. Using CWR22Rv1 cells specifically-labeled with fluorescent probes for autophagosomes and lysosomes, we show that 3D image stacks acquired with either widefield deconvolution microscopy (and later, with super-resolution, structured-illumination microscopy) can clearly capture the early stages of

  10. Quantitative analysis of autophagy using advanced 3D fluorescence microscopy.

    PubMed

    Changou, Chun A; Wolfson, Deanna L; Ahluwalia, Balpreet Singh; Bold, Richard J; Kung, Hsing-Jien; Chuang, Frank Y S

    2013-01-01

    Prostate cancer is the leading form of malignancies among men in the U.S. While surgery carries a significant risk of impotence and incontinence, traditional chemotherapeutic approaches have been largely unsuccessful. Hormone therapy is effective at early stage, but often fails with the eventual development of hormone-refractory tumors. We have been interested in developing therapeutics targeting specific metabolic deficiency of tumor cells. We recently showed that prostate tumor cells specifically lack an enzyme (argininosuccinate synthase, or ASS) involved in the synthesis of the amino acid arginine(1). This condition causes the tumor cells to become dependent on exogenous arginine, and they undergo metabolic stress when free arginine is depleted by arginine deiminase (ADI)(1,10). Indeed, we have shown that human prostate cancer cells CWR22Rv1 are effectively killed by ADI with caspase-independent apoptosis and aggressive autophagy (or macroautophagy)(1,2,3). Autophagy is an evolutionarily-conserved process that allows cells to metabolize unwanted proteins by lysosomal breakdown during nutritional starvation(4,5). Although the essential components of this pathway are well-characterized(6,7,8,9), many aspects of the molecular mechanism are still unclear - in particular, what is the role of autophagy in the death-response of prostate cancer cells after ADI treatment? In order to address this question, we required an experimental method to measure the level and extent of autophagic response in cells - and since there are no known molecular markers that can accurately track this process, we chose to develop an imaging-based approach, using quantitative 3D fluorescence microscopy(11,12). Using CWR22Rv1 cells specifically-labeled with fluorescent probes for autophagosomes and lysosomes, we show that 3D image stacks acquired with either widefield deconvolution microscopy (and later, with super-resolution, structured-illumination microscopy) can clearly capture the early

  11. Quantitative analysis of autophagy using advanced 3D fluorescence microscopy.

    PubMed

    Changou, Chun A; Wolfson, Deanna L; Ahluwalia, Balpreet Singh; Bold, Richard J; Kung, Hsing-Jien; Chuang, Frank Y S

    2013-05-03

    Prostate cancer is the leading form of malignancies among men in the U.S. While surgery carries a significant risk of impotence and incontinence, traditional chemotherapeutic approaches have been largely unsuccessful. Hormone therapy is effective at early stage, but often fails with the eventual development of hormone-refractory tumors. We have been interested in developing therapeutics targeting specific metabolic deficiency of tumor cells. We recently showed that prostate tumor cells specifically lack an enzyme (argininosuccinate synthase, or ASS) involved in the synthesis of the amino acid arginine(1). This condition causes the tumor cells to become dependent on exogenous arginine, and they undergo metabolic stress when free arginine is depleted by arginine deiminase (ADI)(1,10). Indeed, we have shown that human prostate cancer cells CWR22Rv1 are effectively killed by ADI with caspase-independent apoptosis and aggressive autophagy (or macroautophagy)(1,2,3). Autophagy is an evolutionarily-conserved process that allows cells to metabolize unwanted proteins by lysosomal breakdown during nutritional starvation(4,5). Although the essential components of this pathway are well-characterized(6,7,8,9), many aspects of the molecular mechanism are still unclear - in particular, what is the role of autophagy in the death-response of prostate cancer cells after ADI treatment? In order to address this question, we required an experimental method to measure the level and extent of autophagic response in cells - and since there are no known molecular markers that can accurately track this process, we chose to develop an imaging-based approach, using quantitative 3D fluorescence microscopy(11,12). Using CWR22Rv1 cells specifically-labeled with fluorescent probes for autophagosomes and lysosomes, we show that 3D image stacks acquired with either widefield deconvolution microscopy (and later, with super-resolution, structured-illumination microscopy) can clearly capture the early

  12. Crashworthiness analysis using advanced material models in DYNA3D

    SciTech Connect

    Logan, R.W.; Burger, M.J.; McMichael, L.D.; Parkinson, R.D.

    1993-10-22

    As part of an electric vehicle consortium, LLNL and Kaiser Aluminum are conducting experimental and numerical studies on crashworthy aluminum spaceframe designs. They have jointly explored the effect of heat treat on crush behavior and duplicated the experimental behavior with finite-element simulations. The major technical contributions to the state of the art in numerical simulation arise from the development and use of advanced material model descriptions for LLNL`s DYNA3D code. Constitutive model enhancements in both flow and failure have been employed for conventional materials such as low-carbon steels, and also for lighter weight materials such as aluminum and fiber composites being considered for future vehicles. The constitutive model enhancements are developed as extensions from LLNL`s work in anisotropic flow and multiaxial failure modeling. Analysis quality as a function of level of simplification of material behavior and mesh is explored, as well as the penalty in computation cost that must be paid for using more complex models and meshes. The lightweight material modeling technology is being used at the vehicle component level to explore the safety implications of small neighborhood electric vehicles manufactured almost exclusively from these materials.

  13. 3D image analysis of a volcanic deposit

    NASA Astrophysics Data System (ADS)

    de Witte, Y.; Vlassenbroeck, J.; Vandeputte, K.; Dewanckele, J.; Cnudde, V.; van Hoorebeke, L.; Ernst, G.; Jacobs, P.

    2009-04-01

    During the last decades, X-ray micro CT has become a well established technique for non-destructive testing in a wide variety of research fields. Using a series of X-ray transmission images of the sample at different projection angles, a stack of 2D cross-sections is reconstructed, resulting in a 3D volume representing the X-ray attenuation coefficients of the sample. Since the attenuation coefficient of a material depends on its density and atomic number, this volume provides valuable information about the internal structure and composition of the sample. Although much qualitative information can be derived directly from this 3D volume, researchers usually require more quantitative results to be able to provide a full characterization of the sample under investigation. This type of information needs to be retrieved using specialized image processing software. For most samples, it is imperative that this processing is performed on the 3D volume as a whole, since a sequence of 2D cross sections usually forms an inadequate approximation of the actual structure. The complete processing of a volume consists of three sequential steps. First, the volume is segmented into a set of objects. What these objects represent depends on what property of the sample needs to be analysed. The objects can be for instance concavities, dense inclusions or the matrix of the sample. When dealing with noisy data, it might be necessary to filter the data before applying the segmentation. The second step is the separation of connected objects into a set of smaller objects. This is necessary when objects appear to be connected because of the limited resolution and contrast of the scan. Separation can also be useful when the sample contains a network structure and one wants to study the individual cells of the network. The third and last step consists of the actual analysis of the various objects to derive the different parameters of interest. While some parameters require extensive

  14. 3D image analysis of abdominal aortic aneurysm

    NASA Astrophysics Data System (ADS)

    Subasic, Marko; Loncaric, Sven; Sorantin, Erich

    2001-07-01

    In this paper we propose a technique for 3-D segmentation of abdominal aortic aneurysm (AAA) from computed tomography angiography (CTA) images. Output data (3-D model) form the proposed method can be used for measurement of aortic shape and dimensions. Knowledge of aortic shape and size is very important in planning of minimally invasive procedure that is for selection of appropriate stent graft device for treatment of AAA. The technique is based on a 3-D deformable model and utilizes the level-set algorithm for implementation of the method. The method performs 3-D segmentation of CTA images and extracts a 3-D model of aortic wall. Once the 3-D model of aortic wall is available it is easy to perform all required measurements for appropriate stent graft selection. The method proposed in this paper uses the level-set algorithm for deformable models, instead of the classical snake algorithm. The main advantage of the level set algorithm is that it enables easy segmentation of complex structures, surpassing most of the drawbacks of the classical approach. We have extended the deformable model to incorporate the a priori knowledge about the shape of the AAA. This helps direct the evolution of the deformable model to correctly segment the aorta. The algorithm has been implemented in IDL and C languages. Experiments have been performed using real patient CTA images and have shown good results.

  15. 3-D Printed Ultem 9085 Testing and Analysis

    NASA Technical Reports Server (NTRS)

    Aguilar, Daniel; Christensen, Sean; Fox, Emmet J.

    2015-01-01

    The purpose of this document is to analyze the mechanical properties of 3-D printed Ultem 9085. This document will focus on the capabilities, limitations, and complexities of 3D printing in general, and explain the methods by which this material is tested. Because 3-D printing is a relatively new process that offers an innovative means to produce hardware, it is important that the aerospace community understands its current advantages and limitations, so that future endeavors involving 3-D printing may be completely safe. This document encompasses three main sections: a Slosh damage assessment, a destructive test of 3-D printed Ultem 9085 samples, and a test to verify simulation for the 3-D printed SDP (SPHERES Docking Port). Described below, 'Slosh' and 'SDP' refer to two experiments that are built using Ultem 9085 for use with the SPHERES (Synchronized Position Hold, Engage, Reorient, Experimental Satellites) program onboard the International Space Station (ISS) [16]. The SPHERES Facility is managed out of the National Aeronautics and Space Administration (NASA) Ames Research Center in California.

  16. Comparative QSAR studies on peptide deformylase inhibitors.

    PubMed

    Lee, Ji Young; Doddareddy, Munikumar Reddy; Cho, Yong Seo; Choo, Hyunah; Koh, Hun Yeong; Kang, Jae-Hoon; No, Kyoung Tai; Pae, Ae Nim

    2007-05-01

    Comparative quantitative structure-activity relationship (QSAR) analyses of peptide deformylase (PDF) inhibitors were performed with a series of previously published (British Biotech Pharmaceuticals, Oxford, UK) reverse hydroxamate derivatives having antibacterial activity against Escherichia coli PDF, using 2D and 3D QSAR methods, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR). Statistically reliable models with good predictive power were generated from all three methods (CoMFA r (2) = 0.957, q (2) = 0.569; CoMSIA r (2) = 0.924, q (2) = 0.520; HQSAR r (2) = 0.860, q (2) = 0.578). The predictive capability of these models was validated by a set of compounds that were not included in the training set. The models based on CoMFA and CoMSIA gave satisfactory predictive r (2) values of 0.687 and 0.505, respectively. The model derived from the HQSAR method showed a low predictability of 0.178 for the test set. In this study, 3D prediction models showed better predictive power than 2D models for the test set. This might be because 3D information is more important in the case of datasets containing compounds with similar skeletons. Superimposition of CoMFA contour maps in the active site of the PDF crystal structure showed a meaningful correlation between receptor-ligand binding and biological activity. The final QSAR models, along with information gathered from 3D contour and 2D contribution maps, could be useful for the design of novel active inhibitors of PDF. PMID:17333308

  17. Computerized analysis of pelvic incidence from 3D images

    NASA Astrophysics Data System (ADS)

    Vrtovec, Tomaž; Janssen, Michiel M. A.; Pernuš, Franjo; Castelein, René M.; Viergever, Max A.

    2012-02-01

    The sagittal alignment of the pelvis can be evaluated by the angle of pelvic incidence (PI), which is constant for an arbitrary subject position and orientation and can be therefore compared among subjects in standing, sitting or supine position. In this study, PI was measured from three-dimensional (3D) computed tomography (CT) images of normal subjects that were acquired in supine position. A novel computerized method, based on image processing techniques, was developed to automatically determine the anatomical references required to measure PI, i.e. the centers of the femoral heads in 3D, and the center and inclination of the sacral endplate in 3D. Multiplanar image reformation was applied to obtain perfect sagittal views with all anatomical structures completely in line with the hip axis, from which PI was calculated. The resulting PI (mean+/-standard deviation) was equal to 46.6°+/-9.2° for male subjects (N = 189), 47.6°+/-10.7° for female subjects (N = 181), and 47.1°+/-10.0° for all subjects (N = 370). The obtained measurements of PI from 3D images were not biased by acquisition projection or structure orientation, because all anatomical structures were completely in line with the hip axis. The performed measurements in 3D therefore represent PI according to the actual geometrical relationships among anatomical structures of the sacrum, pelvis and hips, as observed from the perfect sagittal views.

  18. Design, biological evaluation and 3D QSAR studies of novel dioxin-containing pyrazoline derivatives with thiourea skeleton as selective HER-2 inhibitors

    PubMed Central

    Yang, Bing; Yang, Yu-Shun; Yang, Na; Li, Guigen; Zhu, Hai-Liang

    2016-01-01

    A series of novel dioxin-containing pyrazoline derivatives with thiourea skeleton have been designed, synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. A majority of them displayed selective HER-2 inhibitory activity against EGFR inhibitory activity. Compound C20 displayed the most potent activity against HER-2 and MDA-MB-453 human breast cancer cell line (IC50 = 0.03 μM and GI50 = 0.15 μM), being slightly more potent than the positive control Erlotinib (IC50 = 0.16 μM and GI50 = 1.56 μM) and comparable with Lapatinib (IC50 = 0.01 μM and GI50 = 0.03 μM). It is a more exciting result that C20 was over 900 times more potent against HER-2 than against EGFR while this value was 0.19 for Erlotinib and 1.00 for Lapatinib, indicating high selectivity. The results of docking simulation indicate that the dioxin moiety occupied the exit of the active pocket and pushed the carbothioamide deep into the active site. QSAR models have been built with activity data and binding conformations to begin our work in this paper as well as to provide a reliable tool for reasonable design of EGFR/HER-2 inhibitors in future. PMID:27273260

  19. Design, biological evaluation and 3D QSAR studies of novel dioxin-containing pyrazoline derivatives with thiourea skeleton as selective HER-2 inhibitors.

    PubMed

    Yang, Bing; Yang, Yu-Shun; Yang, Na; Li, Guigen; Zhu, Hai-Liang

    2016-01-01

    A series of novel dioxin-containing pyrazoline derivatives with thiourea skeleton have been designed, synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. A majority of them displayed selective HER-2 inhibitory activity against EGFR inhibitory activity. Compound C20 displayed the most potent activity against HER-2 and MDA-MB-453 human breast cancer cell line (IC50 = 0.03 μM and GI50 = 0.15 μM), being slightly more potent than the positive control Erlotinib (IC50 = 0.16 μM and GI50 = 1.56 μM) and comparable with Lapatinib (IC50 = 0.01 μM and GI50 = 0.03 μM). It is a more exciting result that C20 was over 900 times more potent against HER-2 than against EGFR while this value was 0.19 for Erlotinib and 1.00 for Lapatinib, indicating high selectivity. The results of docking simulation indicate that the dioxin moiety occupied the exit of the active pocket and pushed the carbothioamide deep into the active site. QSAR models have been built with activity data and binding conformations to begin our work in this paper as well as to provide a reliable tool for reasonable design of EGFR/HER-2 inhibitors in future. PMID:27273260

  20. 3D image analysis of abdominal aortic aneurysm

    NASA Astrophysics Data System (ADS)

    Subasic, Marko; Loncaric, Sven; Sorantin, Erich

    2002-05-01

    This paper presents a method for 3-D segmentation of abdominal aortic aneurysm from computed tomography angiography images. The proposed method is automatic and requires minimal user assistance. Segmentation is performed in two steps. First inner and then outer aortic border is segmented. Those two steps are different due to different image conditions on two aortic borders. Outputs of these two segmentations give a complete 3-D model of abdominal aorta. Such a 3-D model is used in measurements of aneurysm area. The deformable model is implemented using the level-set algorithm due to its ability to describe complex shapes in natural manner which frequently occur in pathology. In segmentation of outer aortic boundary we introduced some knowledge based preprocessing to enhance and reconstruct low contrast aortic boundary. The method has been implemented in IDL and C languages. Experiments have been performed using real patient CTA images and have shown good results.

  1. 3D statistical failure analysis of monolithic dental ceramic crowns.

    PubMed

    Nasrin, Sadia; Katsube, Noriko; Seghi, Robert R; Rokhlin, Stanislav I

    2016-07-01

    For adhesively retained ceramic crown of various types, it has been clinically observed that the most catastrophic failures initiate from the cement interface as a result of radial crack formation as opposed to Hertzian contact stresses originating on the occlusal surface. In this work, a 3D failure prognosis model is developed for interface initiated failures of monolithic ceramic crowns. The surface flaw distribution parameters determined by biaxial flexural tests on ceramic plates and point-to-point variations of multi-axial stress state at the intaglio surface are obtained by finite element stress analysis. They are combined on the basis of fracture mechanics based statistical failure probability model to predict failure probability of a monolithic crown subjected to single-cycle indentation load. The proposed method is verified by prior 2D axisymmetric model and experimental data. Under conditions where the crowns are completely bonded to the tooth substrate, both high flexural stress and high interfacial shear stress are shown to occur in the wall region where the crown thickness is relatively thin while high interfacial normal tensile stress distribution is observed at the margin region. Significant impact of reduced cement modulus on these stress states is shown. While the analyses are limited to single-cycle load-to-failure tests, high interfacial normal tensile stress or high interfacial shear stress may contribute to degradation of the cement bond between ceramic and dentin. In addition, the crown failure probability is shown to be controlled by high flexural stress concentrations over a small area, and the proposed method might be of some value to detect initial crown design errors. PMID:27215334

  2. 3D statistical failure analysis of monolithic dental ceramic crowns.

    PubMed

    Nasrin, Sadia; Katsube, Noriko; Seghi, Robert R; Rokhlin, Stanislav I

    2016-07-01

    For adhesively retained ceramic crown of various types, it has been clinically observed that the most catastrophic failures initiate from the cement interface as a result of radial crack formation as opposed to Hertzian contact stresses originating on the occlusal surface. In this work, a 3D failure prognosis model is developed for interface initiated failures of monolithic ceramic crowns. The surface flaw distribution parameters determined by biaxial flexural tests on ceramic plates and point-to-point variations of multi-axial stress state at the intaglio surface are obtained by finite element stress analysis. They are combined on the basis of fracture mechanics based statistical failure probability model to predict failure probability of a monolithic crown subjected to single-cycle indentation load. The proposed method is verified by prior 2D axisymmetric model and experimental data. Under conditions where the crowns are completely bonded to the tooth substrate, both high flexural stress and high interfacial shear stress are shown to occur in the wall region where the crown thickness is relatively thin while high interfacial normal tensile stress distribution is observed at the margin region. Significant impact of reduced cement modulus on these stress states is shown. While the analyses are limited to single-cycle load-to-failure tests, high interfacial normal tensile stress or high interfacial shear stress may contribute to degradation of the cement bond between ceramic and dentin. In addition, the crown failure probability is shown to be controlled by high flexural stress concentrations over a small area, and the proposed method might be of some value to detect initial crown design errors.

  3. Hybrid segmentation framework for 3D medical image analysis

    NASA Astrophysics Data System (ADS)

    Chen, Ting; Metaxas, Dimitri N.

    2003-05-01

    Medical image segmentation is the process that defines the region of interest in the image volume. Classical segmentation methods such as region-based methods and boundary-based methods cannot make full use of the information provided by the image. In this paper we proposed a general hybrid framework for 3D medical image segmentation purposes. In our approach we combine the Gibbs Prior model, and the deformable model. First, Gibbs Prior models are applied onto each slice in a 3D medical image volume and the segmentation results are combined to a 3D binary masks of the object. Then we create a deformable mesh based on this 3D binary mask. The deformable model will be lead to the edge features in the volume with the help of image derived external forces. The deformable model segmentation result can be used to update the parameters for Gibbs Prior models. These methods will then work recursively to reach a global segmentation solution. The hybrid segmentation framework has been applied to images with the objective of lung, heart, colon, jaw, tumor, and brain. The experimental data includes MRI (T1, T2, PD), CT, X-ray, Ultra-Sound images. High quality results are achieved with relatively efficient time cost. We also did validation work using expert manual segmentation as the ground truth. The result shows that the hybrid segmentation may have further clinical use.

  4. Molecular determinants of ligand binding modes in the histamine H(4) receptor: linking ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models to in silico guided receptor mutagenesis studies.

    PubMed

    Istyastono, Enade P; Nijmeijer, Saskia; Lim, Herman D; van de Stolpe, Andrea; Roumen, Luc; Kooistra, Albert J; Vischer, Henry F; de Esch, Iwan J P; Leurs, Rob; de Graaf, Chris

    2011-12-01

    The histamine H(4) receptor (H(4)R) is a G protein-coupled receptor (GPCR) that plays an important role in inflammation. Similar to the homologous histamine H(3) receptor (H(3)R), two acidic residues in the H(4)R binding pocket, D(3.32) and E(5.46), act as essential hydrogen bond acceptors of positively ionizable hydrogen bond donors in H(4)R ligands. Given the symmetric distribution of these complementary pharmacophore features in H(4)R and its ligands, different alternative ligand binding mode hypotheses have been proposed. The current study focuses on the elucidation of the molecular determinants of H(4)R-ligand binding modes by combining (3D) quantitative structure-activity relationship (QSAR), protein homology modeling, molecular dynamics simulations, and site-directed mutagenesis studies. We have designed and synthesized a series of clobenpropit (N-(4-chlorobenzyl)-S-[3-(4(5)-imidazolyl)propyl]isothiourea) derivatives to investigate H(4)R-ligand interactions and ligand binding orientations. Interestingly, our studies indicate that clobenpropit (2) itself can bind to H(4)R in two distinct binding modes, while the addition of a cyclohexyl group to the clobenpropit isothiourea moiety allows VUF5228 (5) to adopt only one specific binding mode in the H(4)R binding pocket. Our ligand-steered, experimentally supported protein modeling method gives new insights into ligand recognition by H(4)R and can be used as a general approach to elucidate the structure of protein-ligand complexes.

  5. Customisable 3D printed microfluidics for integrated analysis and optimisation.

    PubMed

    Monaghan, T; Harding, M J; Harris, R A; Friel, R J; Christie, S D R

    2016-08-16

    The formation of smart Lab-on-a-Chip (LOC) devices featuring integrated sensing optics is currently hindered by convoluted and expensive manufacturing procedures. In this work, a series of 3D-printed LOC devices were designed and manufactured via stereolithography (SL) in a matter of hours. The spectroscopic performance of a variety of optical fibre combinations were tested, and the optimum path length for performing Ultraviolet-visible (UV-vis) spectroscopy determined. The information gained in these trials was then used in a reaction optimisation for the formation of carvone semicarbazone. The production of high resolution surface channels (100-500 μm) means that these devices were capable of handling a wide range of concentrations (9 μM-38 mM), and are ideally suited to both analyte detection and process optimisation. This ability to tailor the chip design and its integrated features as a direct result of the reaction being assessed, at such a low time and cost penalty greatly increases the user's ability to optimise both their device and reaction. As a result of the information gained in this investigation, we are able to report the first instance of a 3D-printed LOC device with fully integrated, in-line monitoring capabilities via the use of embedded optical fibres capable of performing UV-vis spectroscopy directly inside micro channels. PMID:27452498

  6. Wear Analysis of Thermal Spray Coatings on 3D Surfaces

    NASA Astrophysics Data System (ADS)

    Tillmann, W.; Luo, W.; Selvadurai, U.

    2014-01-01

    Even though the application of thermal spray coatings on complex geometries gained a greater interest in the last decade, the effect of different geometrical features on the wear behavior is still ill-defined. In this study, the wear resistance of FTC-FeCSiMn coated 3D surfaces was investigated. The wear test was carried out by means of two innovative testing procedures. The first test is a Pin-on-Tubes test where the rotating motion is realized by a lathe chuck. The specimens in the second test were fixed on the table and a robot arm operated the pin. This wear test was applied on specimens with concave or convex surfaces. The residual stresses, which were determined by means of an incremental hole-drilling method, show a dependency on the substrate geometry. The obtained stresses were put in relation to the different radii. After the wear test, a 3D-profilometer determined the wear volume and the sections of the coatings were characterized by a scanning electron microscope. The results indicate that the wear resistance is strongly influenced by the geometry of the substrate.

  7. Metrological analysis of the human foot: 3D multisensor exploration

    NASA Astrophysics Data System (ADS)

    Muñoz Potosi, A.; Meneses Fonseca, J.; León Téllez, J.

    2011-08-01

    In the podiatry field, many of the foot dysfunctions are mainly generated due to: Congenital malformations, accidents or misuse of footwear. For the treatment or prevention of foot disorders, the podiatrist diagnoses prosthesis or specific adapted footwear, according to the real dimension of foot. Therefore, it is necessary to acquire 3D information of foot with 360 degrees of observation. As alternative solution, it was developed and implemented an optical system of threedimensional reconstruction based in the principle of laser triangulation. The system is constituted by an illumination unit that project a laser plane into the foot surface, an acquisition unit with 4 CCD cameras placed around of axial foot axis, an axial moving unit that displaces the illumination and acquisition units in the axial axis direction and a processing and exploration unit. The exploration software allows the extraction of distances on three-dimensional image, taking into account the topography of foot. The optical system was tested and their metrological performances were evaluated in experimental conditions. The optical system was developed to acquire 3D information in order to design and make more appropriate footwear.

  8. V3D enables real-time 3D visualization and quantitative analysis of large-scale biological image data sets.

    PubMed

    Peng, Hanchuan; Ruan, Zongcai; Long, Fuhui; Simpson, Julie H; Myers, Eugene W

    2010-04-01

    The V3D system provides three-dimensional (3D) visualization of gigabyte-sized microscopy image stacks in real time on current laptops and desktops. V3D streamlines the online analysis, measurement and proofreading of complicated image patterns by combining ergonomic functions for selecting a location in an image directly in 3D space and for displaying biological measurements, such as from fluorescent probes, using the overlaid surface objects. V3D runs on all major computer platforms and can be enhanced by software plug-ins to address specific biological problems. To demonstrate this extensibility, we built a V3D-based application, V3D-Neuron, to reconstruct complex 3D neuronal structures from high-resolution brain images. V3D-Neuron can precisely digitize the morphology of a single neuron in a fruitfly brain in minutes, with about a 17-fold improvement in reliability and tenfold savings in time compared with other neuron reconstruction tools. Using V3D-Neuron, we demonstrate the feasibility of building a 3D digital atlas of neurite tracts in the fruitfly brain. PMID:20231818

  9. Analysis of patient movement during 3D USCT data acquisition

    NASA Astrophysics Data System (ADS)

    Ruiter, N. V.; Hopp, T.; Zapf, M.; Kretzek, E.; Gemmeke, H.

    2016-04-01

    In our first clinical study with a full 3D Ultrasound Computer Tomography (USCT) system patient data was acquired in eight minutes for one breast. In this paper the patient movement during the acquisition was analyzed quantitatively and as far as possible corrected in the resulting images. The movement was tracked in ten successive reflectivity reconstructions of full breast volumes acquired during 10 s intervals at different aperture positions, which were separated by 41 s intervals. The mean distance between initial and final position was 2.2 mm (standard deviation (STD) +/- 0.9 mm, max. 4.1 mm, min. 0.8 mm) and the average sum of all moved distances was 4.9 mm (STD +/- 1.9 mm, max. 8.8 mm, min. 2.7 mm). The tracked movement was corrected by summing successive images, which were transformed according to the detected movement. The contrast of these images increased and additional image content became visible.

  10. The importance of molecular structures, endpoints' values, and predictivity parameters in QSAR research: QSAR analysis of a series of estrogen receptor binders.

    PubMed

    Li, Jiazhong; Gramatica, Paola

    2010-11-01

    Quantitative structure-activity relationship (QSAR) methodology aims to explore the relationship between molecular structures and experimental endpoints, producing a model for the prediction of new data; the predictive performance of the model must be checked by external validation. Clearly, the qualities of chemical structure information and experimental endpoints, as well as the statistical parameters used to verify the external predictivity have a strong influence on QSAR model reliability. Here, we emphasize the importance of these three aspects by analyzing our models on estrogen receptor binders (Endocrine disruptor knowledge base (EDKB) database). Endocrine disrupting chemicals, which mimic or antagonize the endogenous hormones such as estrogens, are a hot topic in environmental and toxicological sciences. QSAR shows great values in predicting the estrogenic activity and exploring the interactions between the estrogen receptor and ligands. We have verified our previously published model for additional external validation on new EDKB chemicals. Having found some errors in the used 3D molecular conformations, we redevelop a new model using the same data set with corrected structures, the same method (ordinary least-square regression, OLS) and DRAGON descriptors. The new model, based on some different descriptors, is more predictive on external prediction sets. Three different formulas to calculate correlation coefficient for the external prediction set (Q2 EXT) were compared, and the results indicated that the new proposal of Consonni et al. had more reasonable results, consistent with the conclusions from regression line, Williams plot and root mean square error (RMSE) values. Finally, the importance of reliable endpoints values has been highlighted by comparing the classification assignments of EDKB with those of another estrogen receptor binders database (METI): we found that 16.1% assignments of the common compounds were opposite (20 among 124 common

  11. DYNA3D analysis of the DT-20 shipping container

    SciTech Connect

    Logan, R.W.; Lovejoy, S.C.

    1991-08-22

    A DYNA3D model of the DT-20 shipping container was constructed. Impact onto a rigid steel surface at a velocity of 44 ft/sec (30 foot gravity drop) was studied. The orientation of most interest was a side-drop, but end and corner drops were also studied briefly. The assembly for the baseline side impact contained a 150 lb. payload. During this drop, the outer drum sustains plastic strains of up to 0.15, with most the deformation near the rim. The plywood/Celotex packing is crushed about 3 inches. The inner sealed can sees significant stresses, but barely reaches the onset of yielding in some local areas. Based on hand calculations, the bolts joining the can halves could see stresses near 50 ksi. It is felt that overall, the container should survive this drop. However, detailed modeling of the rim closure and the center bolted joint was not possible due to time constraints. Furthermore, better material models and properties are needed for the Celotex, plywood, and honeycomb in particular. 39 figs., 1 tab.

  12. Tensorial analysis of Eshelby stresses in 3D supercooled liquids.

    PubMed

    Lemaître, Anaël

    2015-10-28

    It was recently proposed that the local rearrangements governing relaxation in supercooled liquids impress on the liquid medium long-ranged (Eshelby) stress fluctuations that accumulate over time. From this viewpoint, events must be characterized by elastic dipoles, which are second order tensors, and Eshelby fields are expected to show up in stress and stress increment correlations, which are fourth order tensor fields. We construct here an analytical framework that permits analyzing such tensorial correlations in isotropic media in view of accessing Eshelby fields. Two spherical bases are introduced, which correspond to Cartesian and spherical coordinates for tensors. We show how they can be used to decompose stress correlations and thus test such properties as isotropy and power-law scalings. Eshelby fields and the predicted stress correlations in an infinite medium are shown to belong to an algebra that can conveniently be described using the spherical tensor bases. Using this formalism, we demonstrate that the inherent stress field of 3D supercooled liquids is power law correlated and carries the signature of Eshelby fields, thus supporting the idea that relaxation events give rise to Eshelby stresses that accumulate over time. PMID:26520535

  13. RETRAN-3D MOD003 Peach Bottom Turbine Trip 2 Multidimensional Kinetics Analysis Models and Results

    SciTech Connect

    Mori, Michitsugu; Ogura, Katsunori; Gose, Garry C.; Wu, J.-Y

    2003-04-15

    An analysis of the Peach Bottom Unit 2 Turbine Trip Test 2 (PB2/TT2) has been performed using RETRAN-3D MOD003. The purpose of the analysis was to investigate the PB2/TT2 overpressurization transient using the RETRAN-3D multidimensional kinetics model.

  14. The approximate analysis of the electromagnetic characters of 3-D radome by complex astigmatic wave theory

    NASA Astrophysics Data System (ADS)

    Wang, Yueqing; Wu, Guisheng; Chen, Zhenyang

    The complex astigmatic wave, which imitates the 3-D beam in high-frequency, is an effective method to analyze the electromagnetic characters of the 3-D arbitrarily curved radome. A number of calculations for the ellipsoidal sandwich radome are performed, and the stereoscopic graphics of the results are constructed. Comparing with the experiments, it is shown that this method can be used to simplify analysis and optimization design for many kinds of 3-D radome.

  15. Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N′-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

    PubMed Central

    Sun, Na-Bo; Shi, Yan-Xia; Liu, Xing-Hai; Ma, Yi; Tan, Cheng-Xia; Weng, Jian-Quan; Jin, Jian-Zhong; Li, Bao-Ju

    2013-01-01

    A series of new N,N′-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N′-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N′-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50) of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure–activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study. PMID:24189221

  16. Structure-hepatoprotective activity relationship study of sesquiterpene lactones: A QSAR analysis

    NASA Astrophysics Data System (ADS)

    Paukku, Yuliya; Rasulev, Bakhtiyor; Syrov, Vladimir; Khushbaktova, Zainab; Leszczynski, Jerzy

    This study has been carried out using quantitative structure-activity relationship analysis (QSAR) for 22 sesquiterpene lactones to correlate and predict their hepatoprotective activity. Sesquiterpenoids, the largest class of terpenoids, are a widespread group of substances occurring in various plant organisms. QSAR analysis was carried out using methods such as genetic algorithm for variables selection among generated and calculated descriptors and multiple linear regression analysis. Quantum-chemical calculations have been performed by density functional theory at B3LYP/6-311G(d, p) level for evaluation of electronic properties using reference geometries optimized by semi-empirical AM1 approach. Three models describing hepatoprotective activity values for series of sesquiterpene lactones are proposed. The obtained models are useful for description of sesquiterpene lactones hepatoprotective activity and can be used to estimate the hepatoprotective activity of new substituted sesquiterpene lactones. The models obtained in our study show not only statistical significance, but also good predictive ability. The estimated predictive ability (rtest2) of these models lies within 0.942-0.969.

  17. Reducing Non-Uniqueness in Satellite Gravity Inversion using 3D Object Oriented Image Analysis Techniques

    NASA Astrophysics Data System (ADS)

    Fadel, I.; van der Meijde, M.; Kerle, N.

    2013-12-01

    Non-uniqueness of satellite gravity interpretation has been usually reduced by using a priori information from various sources, e.g. seismic tomography models. The reduction in non-uniqueness has been based on velocity-density conversion formulas or user interpretation for 3D subsurface structures (objects) in seismic tomography models. However, these processes introduce additional uncertainty through the conversion relations due to the dependency on the other physical parameters such as temperature and pressure, or through the bias in the interpretation due to user choices and experience. In this research, a new methodology is introduced to extract the 3D subsurface structures from 3D geophysical data using a state-of-art 3D Object Oriented Image Analysis (OOA) technique. 3D OOA is tested using a set of synthetic models that simulate the real situation in the study area of this research. Then, 3D OOA is used to extract 3D subsurface objects from a real 3D seismic tomography model. The extracted 3D objects are used to reconstruct a forward model and its response is compared with the measured satellite gravity. Finally, the result of the forward modelling, based on the extracted 3D objects, is used to constrain the inversion process of satellite gravity data. Through this work, a new object-based approach is introduced to interpret and extract the 3D subsurface objects from 3D geophysical data. This can be used to constrain modelling and inversion of potential field data using the extracted 3D subsurface structures from other methods. In summary, a new approach is introduced to constrain inversion of satellite gravity measurements and enhance interpretation capabilities.

  18. An optical real-time 3D measurement for analysis of facial shape and movement

    NASA Astrophysics Data System (ADS)

    Zhang, Qican; Su, Xianyu; Chen, Wenjing; Cao, Yiping; Xiang, Liqun

    2003-12-01

    Optical non-contact 3-D shape measurement provides a novel and useful tool for analysis of facial shape and movement in presurgical and postsurgical regular check. In this article we present a system, which allows a precise 3-D visualization of the patient's facial before and after craniofacial surgery. We discussed, in this paper, the real time 3-D image capture, processing and the 3-D phase unwrapping method to recover complex shape deformation when the movement of the mouth. The result of real-time measurement for facial shape and movement will be helpful for the more ideal effect in plastic surgery.

  19. SSME 3-D Turnaround Duct flow analysis - CFD predictions

    NASA Technical Reports Server (NTRS)

    Brankovic, Andreja; Stowers, Steven T.; Mcconnaughey, Paul

    1988-01-01

    CFD analysis is presently employed to obtain an improved flowfield for an individual flowpath in the case of the Space Shuttle Main Engine's High Pressure Fuel Turbopump Turn-Around Duct (TAD), which conducts the flow exiting from the gas turbines into the fuel bowl. It is demonstrated that the application of CFD to TAD flow analysis, giving attention to the duct's configuration and to the number, shape, and alignment of the diffuser struts, can enhance understanding of flow physics and result in improved duct design and performance.

  20. A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs.

    PubMed

    Lee, Sehan; Barron, Mace G

    2016-04-01

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency. PMID:27055524

  1. CheS-Mapper 2.0 for visual validation of (Q)SAR models

    PubMed Central

    2014-01-01

    Background Sound statistical validation is important to evaluate and compare the overall performance of (Q)SAR models. However, classical validation does not support the user in better understanding the properties of the model or the underlying data. Even though, a number of visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allow the investigation of model validation results are still lacking. Results We propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. The approach applies the 3D viewer CheS-Mapper, an open-source application for the exploration of small molecules in virtual 3D space. The present work describes the new functionalities in CheS-Mapper 2.0, that facilitate the analysis of (Q)SAR information and allows the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. The approach is generic: It is model-independent and can handle physico-chemical and structural input features as well as quantitative and qualitative endpoints. Conclusions Visual validation with CheS-Mapper enables analyzing (Q)SAR information in the data and indicates how this information is employed by the (Q)SAR model. It reveals, if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org. Graphical abstract Comparing actual and predicted activity values with CheS-Mapper.

  2. Vector algorithms for geometrically nonlinear 3D finite element analysis

    NASA Technical Reports Server (NTRS)

    Whitcomb, John D.

    1989-01-01

    Algorithms for geometrically nonlinear finite element analysis are presented which exploit the vector processing capability of the VPS-32, which is closely related to the CYBER 205. By manipulating vectors (which are long lists of numbers) rather than individual numbers, very high processing speeds are obtained. Long vector lengths are obtained without extensive replication or reordering by storage of intermediate results in strategic patterns at all stages of the computations. Comparisons of execution times with those from programs using either scalar or other vector programming techniques indicate that the algorithms presented are quite efficient.

  3. Multiscale 3D shape analysis using spherical wavelets.

    PubMed

    Nain, Delphine; Haker, Steven; Bobick, Aaron; Tannenbaum, Allen R

    2005-01-01

    Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data. PMID:16685992

  4. Multiscale 3D Shape Analysis using Spherical Wavelets

    PubMed Central

    Nain, Delphine; Haker, Steven; Bobick, Aaron; Tannenbaum, Allen

    2013-01-01

    Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data. PMID:16685992

  5. 3D inelastic analysis methods for hot section components

    NASA Technical Reports Server (NTRS)

    Dame, L. T.; Chen, P. C.; Hartle, M. S.; Huang, H. T.

    1985-01-01

    The objective is to develop analytical tools capable of economically evaluating the cyclic time dependent plasticity which occurs in hot section engine components in areas of strain concentration resulting from the combination of both mechanical and thermal stresses. Three models were developed. A simple model performs time dependent inelastic analysis using the power law creep equation. The second model is the classical model of Professors Walter Haisler and David Allen of Texas A and M University. The third model is the unified model of Bodner, Partom, et al. All models were customized for linear variation of loads and temperatures with all material properties and constitutive models being temperature dependent.

  6. Understanding the Structural Requirements of Hybrid (S)-6-((2-(4-Phenylpiperazin-1-yl)ethyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol and its Analogs as D2/D3 Receptor Ligands: A Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) Investigation

    PubMed Central

    Modi, Gyan; Sharma, Horrick; Kharkar, Prashant S.; Dutta, Aloke K.

    2014-01-01

    To gain insights into the structural requirements for dopamine D2 and D3 agonists in the treatment of Parkinson’s disease (PD) and to elucidate the basis of selectivity for D3 over D2 (D2/D3), 3D quantitative structure-activity relationship (3D QSAR) investigations using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were performed on a series of 45 structurally related D2 and D3 dopaminergic ligands. Two alignment methods (atom-based and flexible) and two charge calculation methods (Gasteiger-Hückel and AM1) were used in the present study. Overall, D2 affinity and selectivity (D2/D3) models performed better with r2cv values of 0.71 and 0.63 for CoMFA and 0.71 and 0.79 for CoMSIA, respectively. The corresponding predictive r2 values for the CoMFA and CoMSIA models were 0.92 and 0.86 and 0.91 and 0.78, respectively. The CoMFA models generated using flexible alignment outperformed the models with the atom-based alignment in terms of relevant statistics and interpretability of the generated contour maps while CoMSIA models obtained using atom-based alignment showed superiority in terms of internal and external predictive abilities. The presence of carbonyl group (C=O) attached to the piperazine ring and the hydrophobic biphenyl ring were found to be the most important features responsible for the D3 selectivity over D2. This study can be further utilized to design and develop selective and potent dopamine agonists to treat PD. PMID:25221669

  7. Understanding the Structural Requirements of Hybrid (S)-6-((2-(4-Phenylpiperazin-1-yl)ethyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol and its Analogs as D2/D3 Receptor Ligands: A Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) Investigation.

    PubMed

    Modi, Gyan; Sharma, Horrick; Kharkar, Prashant S; Dutta, Aloke K

    2014-09-01

    To gain insights into the structural requirements for dopamine D2 and D3 agonists in the treatment of Parkinson's disease (PD) and to elucidate the basis of selectivity for D3 over D2 (D2/D3), 3D quantitative structure-activity relationship (3D QSAR) investigations using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were performed on a series of 45 structurally related D2 and D3 dopaminergic ligands. Two alignment methods (atom-based and flexible) and two charge calculation methods (Gasteiger-Hückel and AM1) were used in the present study. Overall, D2 affinity and selectivity (D2/D3) models performed better with r(2)cv values of 0.71 and 0.63 for CoMFA and 0.71 and 0.79 for CoMSIA, respectively. The corresponding predictive r(2) values for the CoMFA and CoMSIA models were 0.92 and 0.86 and 0.91 and 0.78, respectively. The CoMFA models generated using flexible alignment outperformed the models with the atom-based alignment in terms of relevant statistics and interpretability of the generated contour maps while CoMSIA models obtained using atom-based alignment showed superiority in terms of internal and external predictive abilities. The presence of carbonyl group (C=O) attached to the piperazine ring and the hydrophobic biphenyl ring were found to be the most important features responsible for the D3 selectivity over D2. This study can be further utilized to design and develop selective and potent dopamine agonists to treat PD.

  8. Sub aquatic 3D visualization and temporal analysis utilizing ArcGIS online and 3D applications

    EPA Science Inventory

    We used 3D Visualization tools to illustrate some complex water quality data we’ve been collecting in the Great Lakes. These data include continuous tow data collected from our research vessel the Lake Explorer II, and continuous water quality data collected from an autono...

  9. Global stability analysis of turbulent 3D wakes

    NASA Astrophysics Data System (ADS)

    Rigas, Georgios; Sipp, Denis; Juniper, Matthew

    2015-11-01

    At low Reynolds numbers, corresponding to laminar and transitional regimes, hydrodynamic stability theory has aided the understanding of the dynamics of bluff body wake-flows and the application of effective control strategies. However, flows of fundamental importance to many industries, in particular the transport industry, involve high Reynolds numbers and turbulent wakes. Despite their turbulence, such wake flows exhibit organisation which is manifested as coherent structures. Recent work has shown that the turbulent coherent structures retain the shape of the symmetry-breaking laminar instabilities and only those manifest as large-scale structures in the near wake (Rigas et al., JFM vol. 750:R5 2014, JFM vol. 778:R2 2015). Based on the findings of the persistence of the laminar instabilities at high Reynolds numbers, we investigate the global stability characteristics of a turbulent wake generated behind a bluff three-dimensional axisymmetric body. We perform a linear global stability analysis on the experimentally obtained mean flow and we recover the dynamic characteristics and spatial structure of the coherent structures, which are linked to the transitional instabilities. A detailed comparison of the predictions with the experimental measurements will be provided.

  10. Code System for Analysis of 3-D Reinforced Concrete Structures.

    1999-11-22

    Version 00 NONSAP-C is a finite element program for determining the static and dynamic response of three-dimensional reinforced concrete structures. Long-term, or creep, behavior of concrete structures can also be analyzed. Nonlinear constitutive relations for concrete under short-term loads are incorporated in two time-independent models, a variable-modulus approach with orthotropic behavior induced in the concrete due to the development of different tangent moduli in different directions and an elastic-plastic model in which the concrete ismore » assumed to be a continuous, isotropic, and linearly elastic-plastic strain-hardening-fracture material. A viscoelastic constitutive model for long-term thermal creep of concrete is included. Three-dimensional finite elements available in NONSAP-C include a truss element, a multinode tendon element for prestressed and post tensioned concrete structures, an elastic-plastic membrane element to represent the behavior of cavity liners, and a general isoparametric element with a variable number of nodes for analysis of solids and thick shells.« less

  11. QSAR analysis and data extrapolation among mammals in a series of aliphatic alcohols

    SciTech Connect

    Tichy, M.; Trcka, V.; Roth, Z.; Krivucova, M.

    1985-09-01

    Concepts of QSAR analysis and biological similarity models are combined for use in extrapolation of LD/sub 50/ values after IP application of a series of aliphatic alcohols (C/sub 1/-C/sub 5/) to mouse, hamster, rat, and guinea pig and rabbit. It has been found that although close correlation exists between LD/sub 50/ values after IP and IV applications for mouse and rat, the QSAR obtained with LD/sub 50/ after IV application are not suitable for a prediction of LD/sub 50/ values after IP application for rabbit. Different transformation or distribution processes in mouse, rat, and rabbit after the two types of applications might be the reason. The LD/sub 50/ values (expressed in mmole/m/sup 2/ of body surface) seem to be independent of mammalian species used (at least within the mouse, rat, hamster, and probably guinea pig series). This fact makes it possible to predict reasonable values of LD/sub 50/ after IP application for rabbit. Expression of toxicity in mmole/m/sup 2/ of body surface may be used in toxicological studies. 24 references, 2 figures, 8 tables.

  12. In silico evaluation, molecular docking and QSAR analysis of quinazoline-based EGFR-T790M inhibitors.

    PubMed

    Asadollahi-Baboli, M

    2016-08-01

    Mutated epidermal growth factor receptor (EGFR-T790M) inhibitors hold promise as new agents against cancer. Molecular docking and QSAR analysis were performed based on a series of fifty-three quinazoline derivatives to elucidate key structural and physicochemical properties affecting inhibitory activity. Molecular docking analysis identified the true conformations of ligands in the receptor's active pocket. The structural features of the ligands, expressed as molecular descriptors, were derived from the obtained docked conformations. Non-linear and spline QSAR models were developed through novel genetic algorithm and artificial neural network (GA-ANN) and multivariate adaptive regression spline techniques, respectively. The former technique was employed to consider non-linear relation between molecular descriptors and inhibitory activity of quinazoline derivatives. The later technique was also used to describe the non-linearity using basis functions and sub-region equations for each descriptor. Our QSAR model gave a high predictive performance [Formula: see text] and [Formula: see text]) using diverse validation techniques. Eight new compounds were designed using our QSAR model as potent EGFR-T790M inhibitors. Overall, the proposed in silico strategy based on docked derived descriptor and non-linear descriptor subset selection may help design novel quinazoline derivatives with improved EGFR-T790M inhibitory activity. PMID:27209475

  13. JULIDE: a software tool for 3D reconstruction and statistical analysis of autoradiographic mouse brain sections.

    PubMed

    Ribes, Delphine; Parafita, Julia; Charrier, Rémi; Magara, Fulvio; Magistretti, Pierre J; Thiran, Jean-Philippe

    2010-11-23

    In this article we introduce JULIDE, a software toolkit developed to perform the 3D reconstruction, intensity normalization, volume standardization by 3D image registration and voxel-wise statistical analysis of autoradiographs of mouse brain sections. This software tool has been developed in the open-source ITK software framework and is freely available under a GPL license. The article presents the complete image processing chain from raw data acquisition to 3D statistical group analysis. Results of the group comparison in the context of a study on spatial learning are shown as an illustration of the data that can be obtained with this tool.

  14. Simplified Deformation Analysis of 3D-body by First Order Analysis

    NASA Astrophysics Data System (ADS)

    Ali Khan, Md. Shawkut; Yamazaki, Koetsu; Oda, Kosuke; Hirooka, Kazuhiko

    This paper proposes a simplified analysis model of complex solid structure for three-dimensional bodies (3D-bodies) in the First Order Analysis (FOA). A simplified finite element composed of the beam elements is suggested for the deformation analysis of 3D-bodies by extending concept of conforming beam element for the finite element method (FEM). When a complex solid structure is simplified to an assemblage of simple elements applied element forces such as axial forces, shear forces, bending moments as well as twisting moments, the total stiffness equation for the FOA of the solid structure is constructed approximately and solved for the given boundary and loading conditions by the usual manner of the FEM. Then, the total deformation of the complex structure is estimated by the simplified model and the element forces are calculated in the element level. It is found that the finite element analysis via developed simplified element analysis can estimate deformations of complex 3D-bodies in a rational precision, and the results of the analysis are useful for considering the load transmitting path of the structure and for designing a better structure by changing the stiffness of structural components.

  15. User's Manual for DuctE3D: A Program for 3D Euler Unsteady Aerodynamic and Aeroelastic Analysis of Ducted Fans

    NASA Technical Reports Server (NTRS)

    Srivastava, R.; Reddy, T. S. R.

    1997-01-01

    The program DuctE3D is used for steady or unsteady aerodynamic and aeroelastic analysis of ducted fans. This guide describes the input data required and the output files generated, in using DuctE3D. The analysis solves three dimensional unsteady, compressible Euler equations to obtain the aerodynamic forces. A normal mode structural analysis is used to obtain the aeroelastic equations, which are solved using either the time domain or the frequency domain solution method. Sample input and output files are included in this guide for steady aerodynamic analysis and aeroelastic analysis of an isolated fan row.

  16. QSAR Analysis of Some Antagonists for p38 map kinase Using Combination of Principal Component Analysis and Artificial Intelligence.

    PubMed

    Doosti, Elham; Shahlaei, Mohsen

    2015-01-01

    Quantitative relationships between structures of a set of p38 map kinase inhibitors and their activities were investigated by principal component regression (PCR) and principal componentartificial neural network (PC-ANN). Latent variables (called components) generated by principal component analysis procedure were applied as the input of developed Quantitative structure- activity relationships (QSAR) models. An exact study of predictability of PCR and PC-ANN showed that the later model has much higher ability to calculate the biological activity of the investigated molecules. Also, experimental and estimated biological activities of compounds used in model development step have indicated a good correlation. Obtained results show that a non-linear model explaining the relationship between the pIC50s and the calculated principal components (that extract from structural descriptors of the studied molecules) is superior than linear model. Some typical figures of merit for QSAR studies explaining the accuracy and predictability of the suggested models were calculated. Therefore, to design novel inhibitors of p38 map kinase with high potency and low undesired effects the developed QSAR models were used to estimate biological pIC50 of the studied compounds.

  17. Comparative QSAR Analysis of 3,5-bis (Arylidene)-4-Piperidone Derivatives: the Development of Predictive Cytotoxicity Models

    PubMed Central

    Edraki, Najmeh; Das, Umashankar; Hemateenejad, Bahram; Dimmock, Jonathan R.; Miri, Ramin

    2016-01-01

    1-[4-(2-Alkylaminoethoxy) phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones are a novel class of potent cytotoxic agents. These compounds demonstrate low micromolar to submicromolar IC50 values against human Molt 4/C8 and CEM T-lymphocytes and murine leukemia L1210 cells. In this study, a comparative QSAR investigation was performed on a series of 3,5-bis (arylidene)-4-piperidones using different chemometric tools to develop the best predictive models for further development of analogs with improved cytotoxicity. All the QSAR models were validated by internal validation tests. The QSAR models obtained by GA-PLS method were considered the best as compared to MLR method. The best QSAR model obtained by GA-PLS analysis on L1210, CEM and Molt4/C8 demonstrated good predictively with R2pred values ranging from 0.94-0.80. Molecular density, topological (X2A) and geometrical indices of the molecules were found to be the most important factors for determining cytotoxic properties. PMID:27642313

  18. Comparative QSAR Analysis of 3,5-bis (Arylidene)-4-Piperidone Derivatives: the Development of Predictive Cytotoxicity Models.

    PubMed

    Edraki, Najmeh; Das, Umashankar; Hemateenejad, Bahram; Dimmock, Jonathan R; Miri, Ramin

    2016-01-01

    1-[4-(2-Alkylaminoethoxy) phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones are a novel class of potent cytotoxic agents. These compounds demonstrate low micromolar to submicromolar IC50 values against human Molt 4/C8 and CEM T-lymphocytes and murine leukemia L1210 cells. In this study, a comparative QSAR investigation was performed on a series of 3,5-bis (arylidene)-4-piperidones using different chemometric tools to develop the best predictive models for further development of analogs with improved cytotoxicity. All the QSAR models were validated by internal validation tests. The QSAR models obtained by GA-PLS method were considered the best as compared to MLR method. The best QSAR model obtained by GA-PLS analysis on L1210, CEM and Molt4/C8 demonstrated good predictively with R(2) pred values ranging from 0.94-0.80. Molecular density, topological (X2A) and geometrical indices of the molecules were found to be the most important factors for determining cytotoxic properties. PMID:27642313

  19. Analysis of the 3D distribution of stacked self-assembled quantum dots by electron tomography

    PubMed Central

    2012-01-01

    The 3D distribution of self-assembled stacked quantum dots (QDs) is a key parameter to obtain the highest performance in a variety of optoelectronic devices. In this work, we have measured this distribution in 3D using a combined procedure of needle-shaped specimen preparation and electron tomography. We show that conventional 2D measurements of the distribution of QDs are not reliable, and only 3D analysis allows an accurate correlation between the growth design and the structural characteristics. PMID:23249477

  20. A 3D-Video-Based Computerized Analysis of Social and Sexual Interactions in Rats

    PubMed Central

    Matsumoto, Jumpei; Urakawa, Susumu; Takamura, Yusaku; Malcher-Lopes, Renato; Hori, Etsuro; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior. PMID:24205238

  1. A 3D-video-based computerized analysis of social and sexual interactions in rats.

    PubMed

    Matsumoto, Jumpei; Urakawa, Susumu; Takamura, Yusaku; Malcher-Lopes, Renato; Hori, Etsuro; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior. PMID:24205238

  2. Mobile 3D quality of experience evaluation: a hybrid data collection and analysis approach

    NASA Astrophysics Data System (ADS)

    Utriainen, Timo; Häyrynen, Jyrki; Jumisko-Pyykkö, Satu; Boev, Atanas; Gotchev, Atanas; Hannuksela, Miska M.

    2011-02-01

    The paper presents a hybrid approach to study the user's experienced quality of 3D visual content on mobile autostereoscopic displays. It combines extensive subjective tests with collection and objective analysis of eye-tracked data. 3D cues which are significant for mobiles are simulated in the generated 3D test content. The methodology for conducting subjective quality evaluation includes hybrid data-collection of quantitative quality preferences, qualitative impressions, and binocular eye-tracking. We present early results of the subjective tests along with eye movement reaction times, areas of interest and heatmaps obtained from raw eye-tracked data after statistical analysis. The study contributes to the question what is important to be visualized on portable auto-stereoscopic displays and how to maintain and visually enhance the quality of 3D content for such displays.

  3. Quantitative Analysis and Modeling of 3-D TSV-Based Power Delivery Architectures

    NASA Astrophysics Data System (ADS)

    He, Huanyu

    As 3-D technology enters the commercial production stage, it is critical to understand different 3-D power delivery architectures on the stacked ICs and packages with through-silicon vias (TSVs). Appropriate design, modeling, analysis, and optimization approaches of the 3-D power delivery system are of foremost significance and great practical interest to the semiconductor industry in general. Based on fundamental physics of 3-D integration components, the objective of this thesis work is to quantitatively analyze the power delivery for 3D-IC systems, develop appropriate physics-based models and simulation approaches, understand the key issues, and provide potential solutions for design of 3D-IC power delivery architectures. In this work, a hybrid simulation approach is adopted as the major approach along with analytical method to examine 3-D power networks. Combining electromagnetic (EM) tools and circuit simulators, the hybrid approach is able to analyze and model micrometer-scale components as well as centimeter-scale power delivery system with high accuracy and efficiency. The parasitic elements of the components on the power delivery can be precisely modeled by full-wave EM solvers. Stack-up circuit models for the 3-D power delivery networks (PDNs) are constructed through a partition and assembly method. With the efficiency advantage of the SPICE circuit simulation, the overall 3-D system power performance can be analyzed and the 3-D power delivery architectures can be evaluated in a short computing time. The major power delivery issues are the voltage drop (IR drop) and voltage noise. With a baseline of 3-D power delivery architecture, the on-chip PDNs of TSV-based chip stacks are modeled and analyzed for the IR drop and AC noise. The basic design factors are evaluated using the hybrid approach, such as the number of stacked chips, the number of TSVs, and the TSV arrangement. Analytical formulas are also developed to evaluate the IR drop in 3-D chip stack in

  4. Sensitivity Analysis of the Scattering-Based SARBM3D Despeckling Algorithm.

    PubMed

    Di Simone, Alessio

    2016-01-01

    Synthetic Aperture Radar (SAR) imagery greatly suffers from multiplicative speckle noise, typical of coherent image acquisition sensors, such as SAR systems. Therefore, a proper and accurate despeckling preprocessing step is almost mandatory to aid the interpretation and processing of SAR data by human users and computer algorithms, respectively. Very recently, a scattering-oriented version of the popular SAR Block-Matching 3D (SARBM3D) despeckling filter, named Scattering-Based (SB)-SARBM3D, was proposed. The new filter is based on the a priori knowledge of the local topography of the scene. In this paper, an experimental sensitivity analysis of the above-mentioned despeckling algorithm is carried out, and the main results are shown and discussed. In particular, the role of both electromagnetic and geometrical parameters of the surface and the impact of its scattering behavior are investigated. Furthermore, a comprehensive sensitivity analysis of the SB-SARBM3D filter against the Digital Elevation Model (DEM) resolution and the SAR image-DEM coregistration step is also provided. The sensitivity analysis shows a significant robustness of the algorithm against most of the surface parameters, while the DEM resolution plays a key role in the despeckling process. Furthermore, the SB-SARBM3D algorithm outperforms the original SARBM3D in the presence of the most realistic scattering behaviors of the surface. An actual scenario is also presented to assess the DEM role in real-life conditions. PMID:27347971

  5. Sensitivity Analysis of the Scattering-Based SARBM3D Despeckling Algorithm

    PubMed Central

    Di Simone, Alessio

    2016-01-01

    Synthetic Aperture Radar (SAR) imagery greatly suffers from multiplicative speckle noise, typical of coherent image acquisition sensors, such as SAR systems. Therefore, a proper and accurate despeckling preprocessing step is almost mandatory to aid the interpretation and processing of SAR data by human users and computer algorithms, respectively. Very recently, a scattering-oriented version of the popular SAR Block-Matching 3D (SARBM3D) despeckling filter, named Scattering-Based (SB)-SARBM3D, was proposed. The new filter is based on the a priori knowledge of the local topography of the scene. In this paper, an experimental sensitivity analysis of the above-mentioned despeckling algorithm is carried out, and the main results are shown and discussed. In particular, the role of both electromagnetic and geometrical parameters of the surface and the impact of its scattering behavior are investigated. Furthermore, a comprehensive sensitivity analysis of the SB-SARBM3D filter against the Digital Elevation Model (DEM) resolution and the SAR image-DEM coregistration step is also provided. The sensitivity analysis shows a significant robustness of the algorithm against most of the surface parameters, while the DEM resolution plays a key role in the despeckling process. Furthermore, the SB-SARBM3D algorithm outperforms the original SARBM3D in the presence of the most realistic scattering behaviors of the surface. An actual scenario is also presented to assess the DEM role in real-life conditions. PMID:27347971

  6. Sensitivity Analysis of the Scattering-Based SARBM3D Despeckling Algorithm.

    PubMed

    Di Simone, Alessio

    2016-01-01

    Synthetic Aperture Radar (SAR) imagery greatly suffers from multiplicative speckle noise, typical of coherent image acquisition sensors, such as SAR systems. Therefore, a proper and accurate despeckling preprocessing step is almost mandatory to aid the interpretation and processing of SAR data by human users and computer algorithms, respectively. Very recently, a scattering-oriented version of the popular SAR Block-Matching 3D (SARBM3D) despeckling filter, named Scattering-Based (SB)-SARBM3D, was proposed. The new filter is based on the a priori knowledge of the local topography of the scene. In this paper, an experimental sensitivity analysis of the above-mentioned despeckling algorithm is carried out, and the main results are shown and discussed. In particular, the role of both electromagnetic and geometrical parameters of the surface and the impact of its scattering behavior are investigated. Furthermore, a comprehensive sensitivity analysis of the SB-SARBM3D filter against the Digital Elevation Model (DEM) resolution and the SAR image-DEM coregistration step is also provided. The sensitivity analysis shows a significant robustness of the algorithm against most of the surface parameters, while the DEM resolution plays a key role in the despeckling process. Furthermore, the SB-SARBM3D algorithm outperforms the original SARBM3D in the presence of the most realistic scattering behaviors of the surface. An actual scenario is also presented to assess the DEM role in real-life conditions.

  7. Quantitative underwater 3D motion analysis using submerged video cameras: accuracy analysis and trajectory reconstruction.

    PubMed

    Silvatti, Amanda P; Cerveri, Pietro; Telles, Thiago; Dias, Fábio A S; Baroni, Guido; Barros, Ricardo M L

    2013-01-01

    In this study we aim at investigating the applicability of underwater 3D motion capture based on submerged video cameras in terms of 3D accuracy analysis and trajectory reconstruction. Static points with classical direct linear transform (DLT) solution, a moving wand with bundle adjustment and a moving 2D plate with Zhang's method were considered for camera calibration. As an example of the final application, we reconstructed the hand motion trajectories in different swimming styles and qualitatively compared this with Maglischo's model. Four highly trained male swimmers performed butterfly, breaststroke and freestyle tasks. The middle fingertip trajectories of both hands in the underwater phase were considered. The accuracy (mean absolute error) of the two calibration approaches (wand: 0.96 mm - 2D plate: 0.73 mm) was comparable to out of water results and highly superior to the classical DLT results (9.74 mm). Among all the swimmers, the hands' trajectories of the expert swimmer in the style were almost symmetric and in good agreement with Maglischo's model. The kinematic results highlight symmetry or asymmetry between the two hand sides, intra- and inter-subject variability in terms of the motion patterns and agreement or disagreement with the model. The two outcomes, calibration results and trajectory reconstruction, both move towards the quantitative 3D underwater motion analysis.

  8. Sketch on dynamic gesture tracking and analysis exploiting vision-based 3D interface

    NASA Astrophysics Data System (ADS)

    Woo, Woontack; Kim, Namgyu; Wong, Karen; Tadenuma, Makoto

    2000-12-01

    In this paper, we propose a vision-based 3D interface exploiting invisible 3D boxes, arranged in the personal space (i.e. reachable space by the body without traveling), which allows robust yet simple dynamic gesture tracking and analysis, without exploiting complicated sensor-based motion tracking systems. Vision-based gesture tracking and analysis is still a challenging problem, even though we have witnessed rapid advances in computer vision over the last few decades. The proposed framework consists of three main parts, i.e. (1) object segmentation without bluescreen and 3D box initialization with depth information, (2) movement tracking by observing how the body passes through the 3D boxes in the personal space and (3) movement feature extraction based on Laban's Effort theory and movement analysis by mapping features to meaningful symbols using time-delay neural networks. Obviously, exploiting depth information using multiview images improves the performance of gesture analysis by reducing the errors introduced by simple 2D interfaces In addition, the proposed box-based 3D interface lessens the difficulties in both tracking movement in 3D space and in extracting low-level features of the movement. Furthermore, the time-delay neural networks lessens the difficulties in movement analysis by training. Due to its simplicity and robustness, the framework will provide interactive systems, such as ATR I-cubed Tangible Music System or ATR Interactive Dance system, with improved quality of the 3D interface. The proposed simple framework also can be extended to other applications requiring dynamic gesture tracking and analysis on the fly.

  9. 3D video analysis of the novel object recognition test in rats.

    PubMed

    Matsumoto, Jumpei; Uehara, Takashi; Urakawa, Susumu; Takamura, Yusaku; Sumiyoshi, Tomiki; Suzuki, Michio; Ono, Taketoshi; Nishijo, Hisao

    2014-10-01

    The novel object recognition (NOR) test has been widely used to test memory function. We developed a 3D computerized video analysis system that estimates nose contact with an object in Long Evans rats to analyze object exploration during NOR tests. The results indicate that the 3D system reproducibly and accurately scores the NOR test. Furthermore, the 3D system captures a 3D trajectory of the nose during object exploration, enabling detailed analyses of spatiotemporal patterns of object exploration. The 3D trajectory analysis revealed a specific pattern of object exploration in the sample phase of the NOR test: normal rats first explored the lower parts of objects and then gradually explored the upper parts. A systematic injection of MK-801 suppressed changes in these exploration patterns. The results, along with those of previous studies, suggest that the changes in the exploration patterns reflect neophobia to a novel object and/or changes from spatial learning to object learning. These results demonstrate that the 3D tracking system is useful not only for detailed scoring of animal behaviors but also for investigation of characteristic spatiotemporal patterns of object exploration. The system has the potential to facilitate future investigation of neural mechanisms underlying object exploration that result from dynamic and complex brain activity. PMID:24991752

  10. QSAR and Molecular Docking Studies of Oxadiazole-Ligated Pyrrole Derivatives as Enoyl-ACP (CoA) Reductase Inhibitors

    PubMed Central

    Asgaonkar, Kalyani D.; Mote, Ganesh D.; Chitre, Trupti S.

    2014-01-01

    A quantitative structure-activity relationship model was developed on a series of compounds containing oxadiazole-ligated pyrrole pharmacophore to identify key structural fragments required for anti-tubercular activity. Two-dimensional (2D) and three-dimensional (3D) QSAR studies were performed using multiple linear regression (MLR) analysis and k-nearest neighbour molecular field analysis (kNN-MFA), respectively. The developed QSAR models were found to be statistically significant with respect to training, cross-validation, and external validation. New chemical entities (NCEs) were designed based on the results of the 2D- and 3D-QSAR. NCEs were subjected to Lipinski’s screen to ensure the drug-like pharmacokinetic profile of the designed compounds in order to improve their bioavailability. Also, the binding ability of the NCEs with enoyl-ACP (CoA) reductase was assessed by docking. PMID:24634843

  11. Development of the PARVMEC Code for Rapid Analysis of 3D MHD Equilibrium

    NASA Astrophysics Data System (ADS)

    Seal, Sudip; Hirshman, Steven; Cianciosa, Mark; Wingen, Andreas; Unterberg, Ezekiel; Wilcox, Robert; ORNL Collaboration

    2015-11-01

    The VMEC three-dimensional (3D) MHD equilibrium has been used extensively for designing stellarator experiments and analyzing experimental data in such strongly 3D systems. Recent applications of VMEC include 2D systems such as tokamaks (in particular, the D3D experiment), where application of very small (delB/B ~ 10-3) 3D resonant magnetic field perturbations render the underlying assumption of axisymmetry invalid. In order to facilitate the rapid analysis of such equilibria (for example, for reconstruction purposes), we have undertaken the task of parallelizing the VMEC code (PARVMEC) to produce a scalable and temporally rapidly convergent equilibrium code for use on parallel distributed memory platforms. The parallelization task naturally splits into three distinct parts 1) radial surfaces in the fixed-boundary part of the calculation; 2) two 2D angular meshes needed to compute the Green's function integrals over the plasma boundary for the free-boundary part of the code; and 3) block tridiagonal matrix needed to compute the full (3D) pre-conditioner near the final equilibrium state. Preliminary results show that scalability is achieved for tasks 1 and 3, with task 2 still nearing completion. The impact of this work on the rapid reconstruction of D3D plasmas using PARVMEC in the V3FIT code will be discussed. Work supported by U.S. DOE under Contract DE-AC05-00OR22725 with UT-Battelle, LLC.

  12. Fully-coupled analysis of jet mixing problems. Three-dimensional PNS model, SCIP3D

    NASA Technical Reports Server (NTRS)

    Wolf, D. E.; Sinha, N.; Dash, S. M.

    1988-01-01

    Numerical procedures formulated for the analysis of 3D jet mixing problems, as incorporated in the computer model, SCIP3D, are described. The overall methodology closely parallels that developed in the earlier 2D axisymmetric jet mixing model, SCIPVIS. SCIP3D integrates the 3D parabolized Navier-Stokes (PNS) jet mixing equations, cast in mapped cartesian or cylindrical coordinates, employing the explicit MacCormack Algorithm. A pressure split variant of this algorithm is employed in subsonic regions with a sublayer approximation utilized for treating the streamwise pressure component. SCIP3D contains both the ks and kW turbulence models, and employs a two component mixture approach to treat jet exhausts of arbitrary composition. Specialized grid procedures are used to adjust the grid growth in accordance with the growth of the jet, including a hybrid cartesian/cylindrical grid procedure for rectangular jets which moves the hybrid coordinate origin towards the flow origin as the jet transitions from a rectangular to circular shape. Numerous calculations are presented for rectangular mixing problems, as well as for a variety of basic unit problems exhibiting overall capabilities of SCIP3D.

  13. 3D finite element analysis of porous Ti-based alloy prostheses.

    PubMed

    Mircheski, Ile; Gradišar, Marko

    2016-11-01

    In this paper, novel designs of porous acetabular cups are created and tested with 3D finite element analysis (FEA). The aim is to develop a porous acetabular cup with low effective radial stiffness of the structure, which will be near to the architectural and mechanical behavior of the natural bone. For the realization of this research, a 3D-scanner technology was used for obtaining a 3D-CAD model of the pelvis bone, a 3D-CAD software for creating a porous acetabular cup, and a 3D-FEA software for virtual testing of a novel design of the porous acetabular cup. The results obtained from this research reveal that a porous acetabular cup from Ti-based alloys with 60 ± 5% porosity has the mechanical behavior and effective radial stiffness (Young's modulus in radial direction) that meet and exceed the required properties of the natural bone. The virtual testing with 3D-FEA of a novel design with porous structure during the very early stage of the design and the development of orthopedic implants, enables obtaining a new or improved biomedical implant for a relatively short time and reduced price.

  14. Spatial and temporal analysis of DIII-D 3D magnetic diagnostic data

    NASA Astrophysics Data System (ADS)

    Strait, E. J.; King, J. D.; Hanson, J. M.; Logan, N. C.

    2016-11-01

    An extensive set of magnetic diagnostics in DIII-D is aimed at measuring non-axisymmetric "3D" features of tokamak plasmas, with typical amplitudes ˜10-3 to 10-5 of the total magnetic field. We describe hardware and software techniques used at DIII-D to condition the individual signals and analysis to estimate the spatial structure from an ensemble of discrete measurements. Applications of the analysis include detection of non-rotating MHD instabilities, plasma control, and validation of MHD stability and 3D equilibrium models.

  15. 3D analysis of eddy current loss in the permanent magnet coupling.

    PubMed

    Zhu, Zina; Meng, Zhuo

    2016-07-01

    This paper first presents a 3D analytical model for analyzing the radial air-gap magnetic field between the inner and outer magnetic rotors of the permanent magnet couplings by using the Amperian current model. Based on the air-gap field analysis, the eddy current loss in the isolation cover is predicted according to the Maxwell's equations. A 3D finite element analysis model is constructed to analyze the magnetic field spatial distributions and vector eddy currents, and then the simulation results obtained are analyzed and compared with the analytical method. Finally, the current losses of two types of practical magnet couplings are measured in the experiment to compare with the theoretical results. It is concluded that the 3D analytical method of eddy current loss in the magnet coupling is viable and could be used for the eddy current loss prediction of magnet couplings. PMID:27475575

  16. 3D analysis of eddy current loss in the permanent magnet coupling

    NASA Astrophysics Data System (ADS)

    Zhu, Zina; Meng, Zhuo

    2016-07-01

    This paper first presents a 3D analytical model for analyzing the radial air-gap magnetic field between the inner and outer magnetic rotors of the permanent magnet couplings by using the Amperian current model. Based on the air-gap field analysis, the eddy current loss in the isolation cover is predicted according to the Maxwell's equations. A 3D finite element analysis model is constructed to analyze the magnetic field spatial distributions and vector eddy currents, and then the simulation results obtained are analyzed and compared with the analytical method. Finally, the current losses of two types of practical magnet couplings are measured in the experiment to compare with the theoretical results. It is concluded that the 3D analytical method of eddy current loss in the magnet coupling is viable and could be used for the eddy current loss prediction of magnet couplings.

  17. Analysis of 3-D images of dental imprints using computer vision

    NASA Astrophysics Data System (ADS)

    Aubin, Michele; Cote, Jean; Laurendeau, Denis; Poussart, Denis

    1992-05-01

    This paper addressed two important aspects of dental analysis: (1) location and (2) identification of the types of teeth by means of 3-D image acquisition and segmentation. The 3-D images of both maxillaries are acquired using a wax wafer as support. The interstices between teeth are detected by non-linear filtering of the 3-D and grey-level data. Two operators are presented: one for the detection of the interstices between incisors, canines, and premolars and one for those between molars. Teeth are then identified by mapping the imprint under analysis on the computer model of an 'ideal' imprint. For the mapping to be valid, a set of three reference points is detected on the imprint. Then, the points are put in correspondence with similar points on the model. Two such points are chosen based on a least-squares fit of a second-order polynomial of the 3-D data in the area of canines. This area is of particular interest since the canines show a very characteristic shape and are easily detected on the imprint. The mapping technique is described in detail in the paper as well as pre-processing of the 3-D profiles. Experimental results are presented for different imprints.

  18. 3D texture analysis for classification of second harmonic generation images of human ovarian cancer

    PubMed Central

    Wen, Bruce; Campbell, Kirby R.; Tilbury, Karissa; Nadiarnykh, Oleg; Brewer, Molly A.; Patankar, Manish; Singh, Vikas; Eliceiri, Kevin. W.; Campagnola, Paul J.

    2016-01-01

    Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class. By applying k-nearest neighbor classification using these learned models, we achieved 83–91% accuracies for the six classes. The 3D method outperformed the analogous 2D classification on the same tissues, where we suggest this is due the increased information content. This classification based on ECM structural changes will complement conventional classification based on genetic profiles and can serve as an additional biomarker. Moreover, the texture analysis algorithm is quite general, as it does not rely on single morphological metrics such as fiber alignment, length, and width but their combined convolution with a customizable basis set. PMID:27767180

  19. Effects of 3D PIV post-processing on impulse and force analysis in vortical flows

    NASA Astrophysics Data System (ADS)

    Mendelson, Leah; Techet, Alexandra

    2014-11-01

    Vortical flows measured using 3D PIV techniques are fundamentally filtered versions of physical phenomena, with velocity information lost below the length and time scales of the measurement system. In the context of propulsive vortices, such as those generated during biological locomotion, these factors, combined with experimental noise and error, can lead to inaccuracies in analysis of the vortex momentum and net thrust. As a result, while 3D velocity measurements remove many of the assumptions required to analyze planar PIV data, they should not be considered absolute physical quantities. Our work focuses on post-processing for 3D PIV data sets to enable the extraction of accurate, quantitative 3D force measurements for unsteady vortical propulsion. In this study, we compare utilizing measurement signal processing techniques, orthogonal decomposition, and identification of coherent structures to measure the impulse of a canonical vortex ring generated by a mechanical piston. In particular, we consider the ability of these methods to confront the influences of limited spatial resolution and arbitrary geometries, and make recommendations for a general procedure for propulsion analysis from 3D PIV data, regardless of which PIV technique is used to obtain the velocity fields.

  20. Comparative Analysis of QSAR-based vs. Chemical Similarity Based Predictors of GPCRs Binding Affinity.

    PubMed

    Luo, Man; Wang, Xiang S; Tropsha, Alexander

    2016-01-01

    Ligand based virtual screening (LBVS) approaches could be broadly divided into those relying on chemical similarity searches and those employing Quantitative Structure-Activity Relationship (QSAR) models. We have compared the predictive power of these approaches using some datasets of compounds tested against several G-Protein Coupled Receptors (GPCRs). The k-Nearest Neighbors (kNN) QSAR models were built for known ligands of each GPCR target independently, with a fraction of tested ligands for each target set aside as a validation set. The prediction accuracies of QSAR models for making active/inactive calls for compounds in both training and validation sets were compared to those achieved by the Prediction of Activity Spectra for Substances' (PASS) and the Similarity Ensemble Approach (SEA) tools both available online. Models developed with the kNN QSAR method showed the highest predictive power for almost all tested GPCR datasets. The PASS software, which incorporates multiple end-point specific QSAR models demonstrated a moderate predictive power, while SEA, a chemical similarity based approach, had the lowest prediction power. Our studies suggest that when sufficient amount of data is available to develop and rigorously validate QSAR models such models should be chosen as the preferred virtual screening tool in ligand-based computational drug discovery as compared to chemical similarity based approaches. PMID:27491652

  1. Discovery of new potent human protein tyrosine phosphatase inhibitors via pharmacophore and QSAR analysis followed by in silico screening.

    PubMed

    Taha, Mutasem O; Bustanji, Yasser; Al-Bakri, Amal G; Yousef, Al-Motassem; Zalloum, Waleed A; Al-Masri, Ihab M; Atallah, Naji

    2007-03-01

    A pharmacophoric model was developed for human protein tyrosine phosphatase 1B (h-PTP 1B) inhibitors utilizing the HipHop-REFINE module of CATALYST software. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of physicochemical descriptors and pharmacophore hypothesis that yield consistent QSAR equation of good predictive potential (r = 0.87,F-statistic = 69.13,r(BS)2 = 0.76,r(LOO)2 = 0.68). The validity of the QSAR equation and the associated pharmacophoric hypothesis was experimentally established by the identification of five new h-PTP 1B inhibitors retrieved from the National Cancer Institute (NCI) database. PMID:17035054

  2. Discovery of new potent human protein tyrosine phosphatase inhibitors via pharmacophore and QSAR analysis followed by in silico screening.

    PubMed

    Taha, Mutasem O; Bustanji, Yasser; Al-Bakri, Amal G; Yousef, Al-Motassem; Zalloum, Waleed A; Al-Masri, Ihab M; Atallah, Naji

    2007-03-01

    A pharmacophoric model was developed for human protein tyrosine phosphatase 1B (h-PTP 1B) inhibitors utilizing the HipHop-REFINE module of CATALYST software. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of physicochemical descriptors and pharmacophore hypothesis that yield consistent QSAR equation of good predictive potential (r = 0.87,F-statistic = 69.13,r(BS)2 = 0.76,r(LOO)2 = 0.68). The validity of the QSAR equation and the associated pharmacophoric hypothesis was experimentally established by the identification of five new h-PTP 1B inhibitors retrieved from the National Cancer Institute (NCI) database.

  3. New insights into high resolution DEM structural analysis with Coltop3D software

    NASA Astrophysics Data System (ADS)

    Metzger, R.; Jaboyedoff, M.; Oppikofer, T.

    2009-04-01

    Modern measurement devices such a terrestrial laser scanning (TLS) systems allow for collecting tremendous amount of (x,y,z) points (up to 20 millions) within a few minutes. However, data analysis still may be impaired because of software limitations, which are usually not designed to handle such huge data sets. To overcome this shortcoming, a software - Coltop3D - was written from scratch. Coltop3D aims at providing the geosciences community a powerful tool to visually handle seamlessly large point clouds and large regular grids DEM, at allowing for straightforward visual analysis of the data with different colour scheme, and at providing specific geologist and/or geoscientist treatment methods such as structural analysis. The main features of Coltop3D are as follow: 1) Ability to handle huge data sets (up to 150 millions points); 2) Coloring the surface with a color scheme linking computer graphics HSV wheel and Schmidt-Lambert stereonet projection; 3) Ability to select a subset of a point cloud with complex geometric shapes; 4) Ability to select a subset of a point cloud with dip and dip direction values; 5) Creating density stereonets with selected subset; 6) Easily import from or export point cloud data to third party software. Besides the technical and basic capabilities of Coltop3D, specific case studies such as structural analysis and rock fall analysis will be presented.

  4. 3-D QSAR ANALYSIS OF INHIBITION OF MURINE SOLUBLE EPOXIDE HYDROLASE (MSEH) BY BENZOYLUREAS, ARYLUREAS, AND THEIR ANALOGUES. (R825433)

    EPA Science Inventory

    Two hundred and seventy-one compounds including benzoylureas, arylureas and related compounds were assayed using recombinant murine soluble epoxide hydrolase (MsEH) produced from a baculovirus expression system. Among all the insect growth regulators assayed, 18 benzoylphenylu...

  5. Image-based RSA: Roentgen stereophotogrammetric analysis based on 2D-3D image registration.

    PubMed

    de Bruin, P W; Kaptein, B L; Stoel, B C; Reiber, J H C; Rozing, P M; Valstar, E R

    2008-01-01

    Image-based Roentgen stereophotogrammetric analysis (IBRSA) integrates 2D-3D image registration and conventional RSA. Instead of radiopaque RSA bone markers, IBRSA uses 3D CT data, from which digitally reconstructed radiographs (DRRs) are generated. Using 2D-3D image registration, the 3D pose of the CT is iteratively adjusted such that the generated DRRs resemble the 2D RSA images as closely as possible, according to an image matching metric. Effectively, by registering all 2D follow-up moments to the same 3D CT, the CT volume functions as common ground. In two experiments, using RSA and using a micromanipulator as gold standard, IBRSA has been validated on cadaveric and sawbone scapula radiographs, and good matching results have been achieved. The accuracy was: |mu |< 0.083 mm for translations and |mu| < 0.023 degrees for rotations. The precision sigma in x-, y-, and z-direction was 0.090, 0.077, and 0.220 mm for translations and 0.155 degrees , 0.243 degrees , and 0.074 degrees for rotations. Our results show that the accuracy and precision of in vitro IBRSA, performed under ideal laboratory conditions, are lower than in vitro standard RSA but higher than in vivo standard RSA. Because IBRSA does not require radiopaque markers, it adds functionality to the RSA method by opening new directions and possibilities for research, such as dynamic analyses using fluoroscopy on subjects without markers and computer navigation applications.

  6. Analysis of scalability of high-performance 3D image processing platform for virtual colonoscopy

    NASA Astrophysics Data System (ADS)

    Yoshida, Hiroyuki; Wu, Yin; Cai, Wenli

    2014-03-01

    One of the key challenges in three-dimensional (3D) medical imaging is to enable the fast turn-around time, which is often required for interactive or real-time response. This inevitably requires not only high computational power but also high memory bandwidth due to the massive amount of data that need to be processed. For this purpose, we previously developed a software platform for high-performance 3D medical image processing, called HPC 3D-MIP platform, which employs increasingly available and affordable commodity computing systems such as the multicore, cluster, and cloud computing systems. To achieve scalable high-performance computing, the platform employed size-adaptive, distributable block volumes as a core data structure for efficient parallelization of a wide range of 3D-MIP algorithms, supported task scheduling for efficient load distribution and balancing, and consisted of a layered parallel software libraries that allow image processing applications to share the common functionalities. We evaluated the performance of the HPC 3D-MIP platform by applying it to computationally intensive processes in virtual colonoscopy. Experimental results showed a 12-fold performance improvement on a workstation with 12-core CPUs over the original sequential implementation of the processes, indicating the efficiency of the platform. Analysis of performance scalability based on the Amdahl's law for symmetric multicore chips showed the potential of a high performance scalability of the HPC 3DMIP platform when a larger number of cores is available.

  7. New technologies of 2-D and 3-D modeling for analysis and management of natural resources

    NASA Astrophysics Data System (ADS)

    Cheremisina, E. N.; Lyubimova, A. V.; Kirpicheva, E. Yu.

    2016-09-01

    For ensuring technological support of research and administrative activity in the sphere of environmental management a specialized modular program complex was developed. The special attention in developing a program complex is focused to creation of convenient and effective tools for creation and visualization 2d and 3D models providing the solution of tasks of the analysis and management of natural resources.

  8. Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) for a 3-D Rigid Wing

    NASA Technical Reports Server (NTRS)

    Gumbert, Clyde R.; Hou, Gene J.-W.; Newman, Perry A.

    1999-01-01

    The formulation and implementation of an optimization method called Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) is presented and applied to a simple 3D wing problem. The method aims to reduce the computational expense incurred in performing shape optimization using state-of-the-art CFD flow analysis and sensitivity analysis tools. Results for this small problem show that the method reaches the same local optimum as conventional optimization methods and does so in about half the computational time.

  9. Value of Computerized 3D Shape Analysis in Differentiating Encapsulated from Invasive Thymomas

    PubMed Central

    Lee, Jong Hyuk; Park, Chang Min; Park, Sang Joon; Bae, Jae Seok; Lee, Sang Min; Goo, Jin Mo

    2015-01-01

    Objectives To retrospectively investigate the added value of quantitative 3D shape analysis in differentiating encapsulated from invasive thymomas. Materials and Methods From February 2002 to October 2013, 53 patients (25 men and 28 women; mean age, 53.94 ± 13.13 years) with 53 pathologically-confirmed thymomas underwent preoperative chest CT scans (slice thicknesses ≤ 2.5 mm). Twenty-three tumors were encapsulated thymomas and 30 were invasive thymomas. Their clinical and CT characteristics were evaluated. In addition, each thymoma was manually-segmented from surrounding structures, and their 3D shape features were assessed using an in-house developed software program. To evaluate the added value of 3D shape features in differentiating encapsulated from invasive thymomas, logistic regression analysis and receiver-operating characteristics curve (ROC) analysis were performed. Results Significant differences were observed between encapsulated and invasive thymomas, in terms of cystic changes (p=0.004), sphericity (p=0.016), and discrete compactness (p=0.001). Subsequent binary logistic regression analysis revealed that absence of cystic change (adjusted odds ratio (OR) = 6.636; p=0.015) and higher discrete compactness (OR = 77.775; p=0.012) were significant differentiators of encapsulated from invasive thymomas. ROC analyses revealed that the addition of 3D shape analysis to clinical and CT features (AUC, 0.955; 95% CI, 0.935–0.975) provided significantly higher performance in differentiating encapsulated from invasive thymomas than clinical and CT features (AUC, 0.666; 95% CI, 0.626–0.707) (p<0.001). Conclusion Addition of 3D shape analysis, particularly discrete compactness, can improve differentiation of encapsulated thymomas from invasive thymomas. PMID:25938505

  10. Numerical Investigation of 3D multichannel analysis of surface wave method

    NASA Astrophysics Data System (ADS)

    Wang, Limin; Xu, Yixian; Luo, Yinhe

    2015-08-01

    Multichannel analysis of surface wave (MASW) method is an efficient tool to obtain near-surface S-wave velocity, and it has gained popularity in engineering practice. Up to now, most examples of using the MASW technique are focused on 2D models or data from a 1D linear receiver spread. We propose a 3D MASW scheme. A finite-difference (FD) method is used to investigate the method using linear and fan-shaped receiver spreads. Results show that the 3D topography strongly affects propagation of Rayleigh waves. The energy concentration of dispersion image is distorted and bifurcated because of the influence of free-surface topography. These effects are reduced with the 3D MASW method. Lastly we investigate the relation between the array size and the resolution of dispersion measurement.

  11. Application of 3D X-ray CT data sets to finite element analysis

    SciTech Connect

    Bossart, P.L.; Martz, H.E.; Brand, H.R.; Hollerbach, K.

    1995-08-31

    Finite Element Modeling (FEM) is becoming more important as industry drives toward concurrent engineering. A fundamental hindrance to fully exploiting the power of FEM is the human effort required to acquire complex part geometry, particularly as-built geometry, as a FEM mesh. Many Quantitative Non Destructive Evaluation (QNDE) techniques that produce three-dimensional (3D) data sets provide a substantial reduction in the effort required to apply FEM to as-built parts. This paper describes progress at LLNL on the application of 3D X-ray computed tomography (CT) data sets to more rapidly produce high-quality FEM meshes of complex, as-built geometries. Issues related to the volume segmentation of the 3D CT data as well as the use of this segmented data to tailor generic hexahedral FEM meshes to part specific geometries are discussed. The application of these techniques to FEM analysis in the medical field is reported here.

  12. A Review of Failure Analysis Methods for Advanced 3D Microelectronic Packages

    NASA Astrophysics Data System (ADS)

    Li, Yan; Srinath, Purushotham Kaushik Muthur; Goyal, Deepak

    2016-01-01

    Advanced three dimensional (3D) packaging is a key enabler in driving form factor reduction, performance benefits, and package cost reduction, especially in the fast paced mobility and ultraportable consumer electronics segments. The high level of functional integration and the complex package architecture pose a significant challenge for conventional fault isolation (FI) and failure analysis (FA) methods. Innovative FI/FA tools and techniques are required to tackle the technical and throughput challenges. In this paper, the applications of FI and FA techniques such as Electro Optic Terahertz Pulse Reflectometry, 3D x-ray computed tomography, lock-in thermography, and novel physical sample preparation methods to 3D packages with package on package and stacked die with through silicon via configurations are reviewed, along with the key FI and FA challenges.

  13. 3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate.

    PubMed

    Gowers, Sally A N; Curto, Vincenzo F; Seneci, Carlo A; Wang, Chu; Anastasova, Salzitsa; Vadgama, Pankaj; Yang, Guang-Zhong; Boutelle, Martyn G

    2015-08-01

    This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime. PMID:26070023

  14. 3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate

    PubMed Central

    2015-01-01

    This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime. PMID:26070023

  15. The DynDom3D Webserver for the Analysis of Domain Movements in Multimeric Proteins.

    PubMed

    Girdlestone, Christopher; Hayward, Steven

    2016-01-01

    DynDom3D is a program for the analysis of domain movements in multimeric proteins. Its inputs are two structure files that indicate a possible domain movement, but the onus has been on the user to process the files so that there is the necessary one-to-one equivalence between atoms in the two atom lists. This is often a prohibitive task to carry out manually, which has limited the application of DynDom3D. Here we report on a webserver with a preprocessor that automatically creates an equivalence between atoms using sequence alignment methods. The processed structure files are passed to DynDom3D and the results are presented on a webpage that includes molecular graphics for easy visualization. PMID:26540459

  16. Finite element analysis of 3D elastic-plastic frictional contact problem for Cosserat materials

    NASA Astrophysics Data System (ADS)

    Zhang, S.; Xie, Z. Q.; Chen, B. S.; Zhang, H. W.

    2013-06-01

    The objective of this paper is to develop a finite element model for 3D elastic-plastic frictional contact problem of Cosserat materials. Because 3D elastic-plastic frictional contact problems belong to the unspecified boundary problems with nonlinearities in both material and geometric forms, a large number of calculations are needed to obtain numerical results with high accuracy. Based on the parametric variational principle and the corresponding quadratic programming method for numerical simulation of frictional contact problems, a finite element model is developed for 3D elastic-plastic frictional contact analysis of Cosserat materials. The problems are finally reduced to linear complementarity problems (LCP). Numerical examples show the feasibility and importance of the developed model for analyzing the contact problems of structures with materials which have micro-polar characteristics.

  17. CX, DPX and PRIDE: WWW servers for the analysis and comparison of protein 3D structures.

    PubMed

    Vlahovicek, Kristian; Pintar, Alessandro; Parthasarathi, Laavanya; Carugo, Oliviero; Pongor, Sándor

    2005-07-01

    The WWW servers at http://www.icgeb.org/protein/ are dedicated to the analysis of protein 3D structures submitted by the users as the Protein Data Bank (PDB) files. CX computes an atomic protrusion index that makes it possible to highlight the protruding atoms within a protein 3D structure. DPX calculates a depth index for the buried atoms and makes it possible to analyze the distribution of buried residues. CX and DPX return PDB files containing the calculated indices that can then be visualized using standard programs, such as Swiss-PDBviewer and Rasmol. PRIDE compares 3D structures using a fast algorithm based on the distribution of inter-atomic distances. The options include pairwise as well as multiple comparisons, and fold recognition based on searching the CATH fold database. PMID:15980464

  18. Towards true 3D textural analysis; using your crystal mush wisely.

    NASA Astrophysics Data System (ADS)

    Jerram, D. A.; Morgan, D. J.; Pankhurst, M. J.

    2014-12-01

    The crystal cargo that is found in volcanic and plutonic rocks contains a wealth of information about magmatic mush processes, crystallisation history, crystal entrainment and recycling. Phenocryst populations predominantly record episodes of growth/nucleation and bulk geochemical changes within an evolving crystal-melt body. Ante- and xeno-crysts provide useful clues to the nature of mush interaction with wall rock and with principal magma(s). Furthermore, crystal evolutions (core to rim) record pathways through pressure, temperature and compositional space. These can often illustrate complex recycling within systems, describing the plumbing architecture. Understanding this architecture underpins our knowledge of how igneous systems can interact with the crust, grow, freeze, re-mobilise and prime for eruption. Initially, 2D studies produced corrected 3D crystal size distributions to help provide information about nucleation and residence times. It immediately became clear that crystal shape is an important factor in determining the confidence placed upon 3D reconstructions of 2D data. Additionally studies utilised serial sections of medium- to coarse-grain-size populations which allowed 3D reconstruction using modelling software to be improved, since size and shape etc. can be directly constrained. Finally the advent of textural studies using X-ray tomography has revolutionised the way in which we can inspect the crystal cargo in mushy systems, allowing us to image in great detail crystal packing arrangements, 3D CSDs, shapes and orientations etc. The latest most innovative studies use X-ray micro-computed tomography to rapidly characterise chemical populations within the crystal cargo, adding a further dimension to this approach, and implies the ability to untangle magmatic chemical components to better understand their individual and combined evolution. In this contribution key examples of the different types of textural analysis techniques in 2D and 3D

  19. Critical body residues linked to octanol-water partitioning, organism composition, and LC50 QSARs: meta-analysis and model.

    PubMed

    Hendriks, A Jan; Traas, Theo P; Huijbregts, Mark A J

    2005-05-01

    To protect thousands of species from thousands of chemicals released in the environment, various risk assessment tools have been developed. Here, we link quantitative structure-activity relationships (QSARs) for response concentrations in water (LC50) to critical concentrations in organisms (C50) by a model for accumulation in lipid or non-lipid phases versus water Kpw. The model indicates that affinity for neutral body components such as storage fat yields steep Kpw-Kow relationships, whereas slopes for accumulation in polar phases such as proteins are gentle. This pattern is confirmed by LC50 QSARs for different modes of action, such as neutral versus polar narcotics and organochlorine versus organophosphor insecticides. LC50 QSARs were all between 0.00002 and 0.2Kow(-1). After calibrating the model with the intercepts and, for the first time also, with the slopes of the LC50 QSARs, critical concentrations in organisms C50 are calculated and compared to an independent validation data set. About 60% of the variability in lethal body burdens C50 is explained by the model. Explanations for differences between estimated and measured levels for 11 modes of action are discussed. In particular, relationships between the critical concentrations in organisms C50 and chemical (Kow) or species (lipid content) characteristics are specified and tested. The analysis combines different models proposed before and provides a substantial extension of the data set in comparison to previous work. Moreover, the concept is applied to species (e.g., plants, lean animals) and substances (e.g., specific modes of action) that were scarcely studied quantitatively so far.

  20. A 3-D biomechanical skeleton model for posture and movement analysis.

    PubMed

    D'Amico, Moreno; D'Amico, Gabriele; Roncoletta, Piero

    2006-01-01

    A project to merge into a full 3D reliable and detailed human skeleton representation various segmental biomechanical models presented in literature has been undertaken by our group. The obtained 3D skeleton model is fully parametric and can so be fitted to each subject anthropometric characteristics. A non-ionizing approach based on 3D opto-electronic measurements of body landmarks labelled by passive markers has been chosen to build the 3D parametric biomechanical skeleton model. To this aim various protocols involving different body labelling (and so different related anthropometric data) have been established for different analyses. To analyse human posture and spinal related pathologies, a 27 markers protocol has been set for static analysis, while 49 markers protocol has been set for gait and movement analysis. A special focus has been devoted to identify and model the spine with a correct degree of accuracy and reliability. To this aim complex signal processing and optimisation procedures have been tested. The model is able to fully integrate information deriving from other measurements devices as force platform data, surface EMG, foot pressure maps. The presented model is the first proposed in literature, to authors knowledge, able to process such multifactorial information to perform a full kinematic and kinetic analysis with particular focus on the spine. Several hundreds of patients have been already analysed and followed up with this methodology that proved to be useful for various posture and spine related pathologies (in particular spine deformities, low-back pain etc.).

  1. Assessment of Altered 3D Blood Characteristics in Aortic Disease by Velocity Distribution Analysis

    PubMed Central

    Garcia, Julio; Barker, Alex J; van Ooij, Pim; Schnell, Susanne; Puthumana, Jyothy; Bonow, Robert O; Collins, Jeremy D; Carr, James C; Markl, Michael

    2014-01-01

    Purpose To test the feasibility of velocity distribution analysis for identifying altered 3D flow characteristics in patients with aortic disease based on 4D flow MRI volumetric analysis. Methods Forty patients with aortic (Ao) dilation (mid ascending aortic diameter MAA=40±7 mm, age=56±17 yr, 11 females) underwent cardiovascular MRI. Four groups were retrospectively defined: mild Ao dilation (n=10, MAA<35 mm); moderate Ao dilation (n=10, 3545 mm); Ao dilation+aortic stenosis AS (n=10, MAA>35 mm and peak velocity >2.5m/s). 3D PC-MR angiograms were computed and used to obtain a 3D segmentation of the aorta which was divided into four segments: root, ascending aorta, arch, descending aorta. Radial chart displays were used to visualize multiple parameters representing segmental changes in the 3D velocity distribution associated with aortic disease. Results Changes in the velocity field and geometry between cohorts resulted in distinct hemodynamic patterns for each aortic segment. Disease progression from mild to Ao dilation+AS resulted in significant differences (P<0.05) in flow parameters across cohorts and increased radial chart size for root and ascending aorta segments by 146% and 99%, respectively. Conclusion Volumetric 4D velocity distribution analysis has the potential to identify characteristic changes in regional blood flow patterns in patients with aortic disease. PMID:25252029

  2. Exploratory Climate Data Visualization and Analysis Using DV3D and UVCDAT

    NASA Technical Reports Server (NTRS)

    Maxwell, Thomas

    2012-01-01

    Earth system scientists are being inundated by an explosion of data generated by ever-increasing resolution in both global models and remote sensors. Advanced tools for accessing, analyzing, and visualizing very large and complex climate data are required to maintain rapid progress in Earth system research. To meet this need, NASA, in collaboration with the Ultra-scale Visualization Climate Data Analysis Tools (UVCOAT) consortium, is developing exploratory climate data analysis and visualization tools which provide data analysis capabilities for the Earth System Grid (ESG). This paper describes DV3D, a UV-COAT package that enables exploratory analysis of climate simulation and observation datasets. OV3D provides user-friendly interfaces for visualization and analysis of climate data at a level appropriate for scientists. It features workflow inte rfaces, interactive 40 data exploration, hyperwall and stereo visualization, automated provenance generation, and parallel task execution. DV30's integration with CDAT's climate data management system (COMS) and other climate data analysis tools provides a wide range of high performance climate data analysis operations. DV3D expands the scientists' toolbox by incorporating a suite of rich new exploratory visualization and analysis methods for addressing the complexity of climate datasets.

  3. PROP3D: A Program for 3D Euler Unsteady Aerodynamic and Aeroelastic (Flutter and Forced Response) Analysis of Propellers. Version 1.0

    NASA Technical Reports Server (NTRS)

    Srivastava, R.; Reddy, T. S. R.

    1996-01-01

    This guide describes the input data required, for steady or unsteady aerodynamic and aeroelastic analysis of propellers and the output files generated, in using PROP3D. The aerodynamic forces are obtained by solving three dimensional unsteady, compressible Euler equations. A normal mode structural analysis is used to obtain the aeroelastic equations, which are solved using either time domain or frequency domain solution method. Sample input and output files are included in this guide for steady aerodynamic analysis of single and counter-rotation propellers, and aeroelastic analysis of single-rotation propeller.

  4. High-resolution 3D micro-CT imaging of breast microcalcifications: a preliminary analysis

    PubMed Central

    2014-01-01

    Background Detection of microcalcifications on mammograms indicates the presence of breast lesion, and the shapes of the microcalcifications as seen by conventional mammography correlates with the probability of malignancy. This preliminary study evaluated the 3D shape of breast microcalcifications using micro-computed tomography (micro-CT) and compared the findings with those obtained using anatomopathological analysis. Methods The study analyzed breast biopsy samples from 11 women with findings of suspicious microcalcifications on routine mammograms. The samples were imaged using a micro-CT (SkyScan 1076) at a resolution of 35 μm. Images were reconstructed using filtered back-projection and analyzed in 3D using surface rendering. The samples were subsequently analyzed by the pathology service. Reconstructed 3D images were compared with the corresponding histological slices. Results Anatomopathological analysis showed that 5 of 11 patients had ductal breast carcinoma in situ. One patient was diagnosed with invasive ductal carcinoma. Individual object analysis was performed on 597 microcalcifications. Malignant microcalcifications tended to be thinner and to have a smaller volume and surface area, while their surface area-to-volume ratio was greater than that of benign microcalcifications. The structure model index values were the same for malignant and benign microcalcifications. Conclusions This is the first study to use micro-CT for quantitative 3D analysis of microcalcifications. This high-resolution imaging technique will be valuable for gaining a greater understanding of the morphologic characteristics of malignant and benign microcalcifications. The presence of many small microcalcifications can be an indication of malignancy. For the larger microcalcifications, 3D parameters confirmed the more irregular shape of malignant microcalcifications. PMID:24393444

  5. A 3-D aerodynamic method for the analysis of isolated horizontal-axis wind turbines

    SciTech Connect

    Ammara, I.; Masson, C.; Paraschivoiu, I.

    1997-12-31

    In most existing performance-analysis methods, wind turbines are considered isolated so that interference effects caused by other rotors or by the site topography are neglected. The main objective of this paper is to propose a practical 3-D method suitable for the study of these effects, in order to optimize the arrangement and the positioning of Horizontal-Axis Wind Turbines (HAWTs) in a wind farm. In the proposed methodology, the flow field around isolated HAWTs is predicted by solving the 3-D, time-averaged, steady-state, incompressible, Navier-Stokes equations in which the turbines are represented by distributions of momentum sources. The resulting governing equations are solved using a Control-Volume Finite Element Method (CVFEM). The fundamental aspects related to the development of a practical 3-D method are discussed in this paper, with an emphasis on some of the challenges that arose during its implementation. The current implementation is limited to the analysis of isolated HAWTs. Preliminary results have indicated that, the proposed 3-D method reaches the same level of accuracy, in terms of performance predictions, that the previously developed 2-D axisymmetric model and the well-known momentum-strip theory, while still using reasonable computers resources. It can be considered as a useful tool for the design of HAWTs. Its main advantages, however, are its intrinsic capacity to predict the details of the flow in the wake, and its capabilities of modelling arbitrary wind-turbine arrangements and including ground effects.

  6. Geomorphometric analysis of cave ceiling channels mapped with 3-D terrestrial laser scanning

    NASA Astrophysics Data System (ADS)

    Gallay, Michal; Hochmuth, Zdenko; Kaňuk, Ján; Hofierka, Jaroslav

    2016-05-01

    The change of hydrological conditions during the evolution of caves in carbonate rocks often results in a complex subterranean geomorphology, which comprises specific landforms such as ceiling channels, anastomosing half tubes, or speleothems organized vertically in different levels. Studying such complex environments traditionally requires tedious mapping; however, this is being replaced with terrestrial laser scanning technology. Laser scanning overcomes the problem of reaching high ceilings, providing new options to map underground landscapes with unprecedented level of detail and accuracy. The acquired point cloud can be handled conveniently with dedicated software, but applying traditional geomorphometry to analyse the cave surface is limited. This is because geomorphometry has been focused on parameterization and analysis of surficial terrain. The theoretical and methodological concept has been based on two-dimensional (2-D) scalar fields, which are sufficient for most cases of the surficial terrain. The terrain surface is modelled with a bivariate function of altitude (elevation) and represented by a raster digital elevation model. However, the cave is a 3-D entity; therefore, a different approach is required for geomorphometric analysis. In this paper, we demonstrate the benefits of high-resolution cave mapping and 3-D modelling to better understand the palaeohydrography of the Domica cave in Slovakia. This methodological approach adopted traditional geomorphometric methods in a unique manner and also new methods used in 3-D computer graphics, which can be applied to study other 3-D geomorphological forms.

  7. Quantification of Dynamic Morphological Drug Responses in 3D Organotypic Cell Cultures by Automated Image Analysis

    PubMed Central

    Härmä, Ville; Schukov, Hannu-Pekka; Happonen, Antti; Ahonen, Ilmari; Virtanen, Johannes; Siitari, Harri; Åkerfelt, Malin; Lötjönen, Jyrki; Nees, Matthias

    2014-01-01

    Glandular epithelial cells differentiate into complex multicellular or acinar structures, when embedded in three-dimensional (3D) extracellular matrix. The spectrum of different multicellular morphologies formed in 3D is a sensitive indicator for the differentiation potential of normal, non-transformed cells compared to different stages of malignant progression. In addition, single cells or cell aggregates may actively invade the matrix, utilizing epithelial, mesenchymal or mixed modes of motility. Dynamic phenotypic changes involved in 3D tumor cell invasion are sensitive to specific small-molecule inhibitors that target the actin cytoskeleton. We have used a panel of inhibitors to demonstrate the power of automated image analysis as a phenotypic or morphometric readout in cell-based assays. We introduce a streamlined stand-alone software solution that supports large-scale high-content screens, based on complex and organotypic cultures. AMIDA (Automated Morphometric Image Data Analysis) allows quantitative measurements of large numbers of images and structures, with a multitude of different spheroid shapes, sizes, and textures. AMIDA supports an automated workflow, and can be combined with quality control and statistical tools for data interpretation and visualization. We have used a representative panel of 12 prostate and breast cancer lines that display a broad spectrum of different spheroid morphologies and modes of invasion, challenged by a library of 19 direct or indirect modulators of the actin cytoskeleton which induce systematic changes in spheroid morphology and differentiation versus invasion. These results were independently validated by 2D proliferation, apoptosis and cell motility assays. We identified three drugs that primarily attenuated the invasion and formation of invasive processes in 3D, without affecting proliferation or apoptosis. Two of these compounds block Rac signalling, one affects cellular cAMP/cGMP accumulation. Our approach supports

  8. QSAR and molecular docking studies on oxindole derivatives as VEGFR-2 tyrosine kinase inhibitors.

    PubMed

    Kang, Cong-Min; Liu, Dong-Qing; Zhao, Xu-Hao; Dai, Ying-Jie; Cheng, Jia-Gao; Lv, Ying-Tao

    2016-01-01

    The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 30 oxindole derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis comparative molecular similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated value (R(2)) was 0.987, and the external cross-validated value ([Formula: see text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and [Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking studies were employed to bind the inhibitors into the active site to determine the probable binding conformation. The binding mode obtained by molecular docking was in good agreement with the 3D-QSAR results. Based on the QSAR models and the docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were designed, which showed excellent predicting inhibiting potencies. The result revealed that both QSAR models have good predictive capability to guide the design and structural modification of homologic compounds. It is also helpful for further research and development of new VEGFR-2 tyrosine kinase inhibitors.

  9. Discrimination of Rhizoma Gastrodiae (Tianma) using 3D synchronous fluorescence spectroscopy coupled with principal component analysis

    NASA Astrophysics Data System (ADS)

    Fan, Qimeng; Chen, Chaoyin; Huang, Zaiqiang; Zhang, Chunmei; Liang, Pengjuan; Zhao, Shenglan

    2015-02-01

    Rhizoma Gastrodiae (Tianma) of different variants and different geographical origins has vital difference in quality and physiological efficacy. This paper focused on the classification and identification of Tianma of six types (two variants from three different geographical origins) using three dimensional synchronous fluorescence spectroscopy (3D-SFS) coupled with principal component analysis (PCA). 3D-SF spectra of aqueous extracts, which were obtained from Tianma of the six types, were measured by a LS-50B luminescence spectrofluorometer. The experimental results showed that the characteristic fluorescent spectral regions of the 3D-SF spectra were similar, while the intensities of characteristic regions are different significantly. Coupled these differences in peak intensities with PCA, Tianma of six types could be discriminated successfully. In conclusion, 3D-SFS coupled with PCA, which has such advantages as effective, specific, rapid, non-polluting, has an edge for discrimination of the similar Chinese herbal medicine. And the proposed methodology is a useful tool to classify and identify Tianma of different variants and different geographical origins.

  10. Descriptors and their selection methods in QSAR analysis: paradigm for drug design.

    PubMed

    Danishuddin; Khan, Asad U

    2016-08-01

    The screening of chemical libraries with traditional methods, such as high-throughput screening (HTS), is expensive and time consuming. Quantitative structure-activity relation (QSAR) modeling is an alternative method that can assist in the selection of lead molecules by using the information from reference active and inactive compounds. This approach requires good molecular descriptors that are representative of the molecular features responsible for the relevant molecular activity. The usefulness of these descriptors in QSAR studies has been extensively demonstrated, and they have also been used as a measure of structural similarity or diversity. In this review, we provide a brief explanation of descriptors and the selection approaches most commonly used in QSAR experiments. In addition, some studies have also demonstrated the positive influence of features selection for any drug development model. PMID:27326911

  11. QSAR analyses of DDT analogues and their in silico validation using molecular docking study against voltage-gated sodium channel of Anopheles funestus.

    PubMed

    Saini, V; Kumar, A

    2014-01-01

    DDT has enjoyed the reputation of a successful pesticide in disease control programme and agricultural practices along with the serious opposition and ban later on due to its biomagnification and toxic action against non-target organisms. The present work was carried out to develop QSAR models for analysing DDT analogues for their pesticidal activity and in silico validation of these models. A 2D-QSAR model was generated using stepwise with multiple regression, and the model with a value of r(2) = 0.7324; q(2) = 0.6215; pred r(2) = 0.7038, containing five descriptors, was selected for further study. The 3D QSAR with CoMFA analysis showed that steric contribution of 21% and electrostatic contribution of about 79% were required for larvicidal activity of DDT analogues. A set of 3430 molecules was generated using the basic DDT skeleton as template, and these were evaluated for their mosquito larvicidal activity using the generated QSAR models and DDT as standard. Eleven molecules were selected for in silico validation of these models. For this, a docking study of the selected molecules against the homology-modelled voltage-gated sodium channel of Anopheles funestus was conducted. The study showed that the activities of these analogues as predicted by 2D-QSAR, 3D-QSAR with CoMFA and dock score were observed to be well correlated.

  12. QSAR analyses of DDT analogues and their in silico validation using molecular docking study against voltage-gated sodium channel of Anopheles funestus.

    PubMed

    Saini, V; Kumar, A

    2014-01-01

    DDT has enjoyed the reputation of a successful pesticide in disease control programme and agricultural practices along with the serious opposition and ban later on due to its biomagnification and toxic action against non-target organisms. The present work was carried out to develop QSAR models for analysing DDT analogues for their pesticidal activity and in silico validation of these models. A 2D-QSAR model was generated using stepwise with multiple regression, and the model with a value of r(2) = 0.7324; q(2) = 0.6215; pred r(2) = 0.7038, containing five descriptors, was selected for further study. The 3D QSAR with CoMFA analysis showed that steric contribution of 21% and electrostatic contribution of about 79% were required for larvicidal activity of DDT analogues. A set of 3430 molecules was generated using the basic DDT skeleton as template, and these were evaluated for their mosquito larvicidal activity using the generated QSAR models and DDT as standard. Eleven molecules were selected for in silico validation of these models. For this, a docking study of the selected molecules against the homology-modelled voltage-gated sodium channel of Anopheles funestus was conducted. The study showed that the activities of these analogues as predicted by 2D-QSAR, 3D-QSAR with CoMFA and dock score were observed to be well correlated. PMID:25271473

  13. Statistical 3D shape analysis of gender differences in lateral ventricles

    NASA Astrophysics Data System (ADS)

    He, Qing; Karpman, Dmitriy; Duan, Ye

    2010-03-01

    This paper aims at analyzing gender differences in the 3D shapes of lateral ventricles, which will provide reference for the analysis of brain abnormalities related to neurological disorders. Previous studies mostly focused on volume analysis, and the main challenge in shape analysis is the required step of establishing shape correspondence among individual shapes. We developed a simple and efficient method based on anatomical landmarks. 14 females and 10 males with matching ages participated in this study. 3D ventricle models were segmented from MR images by a semiautomatic method. Six anatomically meaningful landmarks were identified by detecting the maximum curvature point in a small neighborhood of a manually clicked point on the 3D model. Thin-plate spline was used to transform a randomly selected template shape to each of the rest shape instances, and the point correspondence was established according to Euclidean distance and surface normal. All shapes were spatially aligned by Generalized Procrustes Analysis. Hotelling T2 twosample metric was used to compare the ventricle shapes between males and females, and False Discovery Rate estimation was used to correct for the multiple comparison. The results revealed significant differences in the anterior horn of the right ventricle.

  14. 3D cephalometric analysis obtained from computed tomography. Review of the literature

    PubMed Central

    Rossini, Giulia; Cavallini, Costanza; Cassetta, Michele; Barbato, Ersilia

    2012-01-01

    Summary Introduction The aim of this systematic review is to estimate accuracy and reproducibility of craniometric measurements and reliability of landmarks identified with computed tomography (CT) techniques in 3D cephalometric analysis. Methods Computerized and manual searches were conducted up to 2011 for studies that addressed these objectives. The selection criteria were: (1) the use of human specimen; (2) the comparison between 2D and 3D cephalometric analysis; (3) the assessment of accuracy, reproducibility of measurements and reliability of landmark identification with CT images compared with two-dimensional conventional radiographs. The Cochrane Handbook for Systematic Reviews of Interventions was used as the guideline for this article. Results Twenty-seven articles met the inclusion criteria. Most of them demonstrated high measurements accuracy and reproducibility, and landmarks reliability, but their cephalometric analysis methodology varied widely. Conclusion These differencies among the studies in making measurements don’t permit a direct comparison between them. The future developments in the knowledge of these techniques should provide a standardized method to conduct the 3D CT cephalometric analysis. PMID:22545187

  15. On 3-D inelastic analysis methods for hot section components. Volume 1: Special finite element models

    NASA Technical Reports Server (NTRS)

    Nakazawa, S.

    1988-01-01

    This annual status report presents the results of work performed during the fourth year of the 3-D Inelastic Analysis Methods for Hot Section Components program (NASA Contract NAS3-23697). The objective of the program is to produce a series of new computer codes permitting more accurate and efficient 3-D analysis of selected hot section components, i.e., combustor liners, turbine blades and turbine vanes. The computer codes embody a progression of math models and are streamlined to take advantage of geometrical features, loading conditions, and forms of material response that distinguish each group of selected components. Volume 1 of this report discusses the special finite element models developed during the fourth year of the contract.

  16. Shape analysis of corpus callosum in phenylketonuria using a new 3D correspondence algorithm

    NASA Astrophysics Data System (ADS)

    He, Qing; Christ, Shawn E.; Karsch, Kevin; Peck, Dawn; Duan, Ye

    2010-03-01

    Statistical shape analysis of brain structures has gained increasing interest from neuroimaging community because it can precisely locate shape differences between healthy and pathological structures. The most difficult and crucial problem is establishing shape correspondence among individual 3D shapes. This paper proposes a new algorithm for 3D shape correspondence. A set of landmarks are sampled on a template shape, and initial correspondence is established between the template and the target shape based on the similarity of locations and normal directions. The landmarks on the target are then refined by iterative thin plate spline. The algorithm is simple and fast, and no spherical mapping is needed. We apply our method to the statistical shape analysis of the corpus callosum (CC) in phenylketonuria (PKU), and significant local shape differences between the patients and the controls are found in the most anterior and posterior aspects of the corpus callosum.

  17. 3D CT Imaging for Craniofacial Analysis Based on Anatomical Regions.

    PubMed

    Wan Harun, W A R; Ahmad Rajion, Zainul; Abdul Aziz, Izhar; Rani Samsudin, Abdul

    2005-01-01

    The development of a craniofacial database is a multidisciplinary initiative that will provide an important reference for community, security, social and medical applications. A method of landmark identifications and measurements in 3d on craniofacial patients is described. anatomical regions such as mandible, orbits, zygoma and maxilla are located, created and stored as templates of 3D CAD files for subsequent analysis. Data from these images were tested for accuracy and repeatability by comparing with direct measurements using caliper and CMM. The landmark points are reproducible in CAD system for further analysis. it was found that the approach provides a fast, accurate and efficient method for landmarks identification of the craniofacial areas in database development. PMID:17282309

  18. 3D visualization environment for analysis of telehealth indicators in public health.

    PubMed

    Filho, Amadeu S Campos; Novaes, Magdala A; Gomes, Alex S

    2013-01-01

    With the growth of telehealth applications and the need for public health managers to have tools that facilitate visualization of indicators produced by telehealth services arose the need to have simple systems to better planning the interventions. Furthermore, Health systems are considers difficult in order to visualize the right information by many health professionals [1] because of the complexity of its Graphical User Interface (GUI) and the high cognitive load needed to handle it. To overcome this problem, we have proposed a 3D environment for the analysis of telehealth indicators in public health by managers of public health sites. Users who will use the environment are part of public health manager of family health sites that participate of Network of Telehealth Centers of Pernambuco (RedeNUTES) [2] that is part of Brazil telehealth program. This paper aims to present a 3D environment for analysis of telehealth indicators by public health manager.

  19. Importance of a 3D forward modeling tool for surface wave analysis methods

    NASA Astrophysics Data System (ADS)

    Pageot, Damien; Le Feuvre, Mathieu; Donatienne, Leparoux; Philippe, Côte; Yann, Capdeville

    2016-04-01

    Since a few years, seismic surface waves analysis methods (SWM) have been widely developed and tested in the context of subsurface characterization and have demonstrated their effectiveness for sounding and monitoring purposes, e.g., high-resolution tomography of the principal geological units of California or real time monitoring of the Piton de la Fournaise volcano. Historically, these methods are mostly developed under the assumption of semi-infinite 1D layered medium without topography. The forward modeling is generally based on Thomson-Haskell matrix based modeling algorithm and the inversion is driven by Monte-Carlo sampling. Given their efficiency, SWM have been transfered to several scale of which civil engineering structures in order to, e.g., determine the so-called V s30 parameter or assess other critical constructional parameters in pavement engineering. However, at this scale, many structures may often exhibit 3D surface variations which drastically limit the efficiency of SWM application. Indeed, even in the case of an homogeneous structure, 3D geometry can bias the dispersion diagram of Rayleigh waves up to obtain discontinuous phase velocity curves which drastically impact the 1D mean velocity model obtained from dispersion inversion. Taking advantages of high-performance computing center accessibility and wave propagation modeling algorithm development, it is now possible to consider the use of a 3D elastic forward modeling algorithm instead of Thomson-Haskell method in the SWM inversion process. We use a parallelized 3D elastic modeling code based on the spectral element method which allows to obtain accurate synthetic data with very low numerical dispersion and a reasonable numerical cost. In this study, we choose dike embankments as an illustrative example. We first show that their longitudinal geometry may have a significant effect on dispersion diagrams of Rayleigh waves. Then, we demonstrate the necessity of 3D elastic modeling as a forward

  20. Strategy and software for the statistical spatial analysis of 3D intracellular distributions.

    PubMed

    Biot, Eric; Crowell, Elizabeth; Burguet, Jasmine; Höfte, Herman; Vernhettes, Samantha; Andrey, Philippe

    2016-07-01

    The localization of proteins in specific domains or compartments in the 3D cellular space is essential for many fundamental processes in eukaryotic cells. Deciphering spatial organization principles within cells is a challenging task, in particular because of the large morphological variations between individual cells. We present here an approach for normalizing variations in cell morphology and for statistically analyzing spatial distributions of intracellular compartments from collections of 3D images. The method relies on the processing and analysis of 3D geometrical models that are generated from image stacks and that are used to build representations at progressively increasing levels of integration, ultimately revealing statistical significant traits of spatial distributions. To make this methodology widely available to end-users, we implemented our algorithmic pipeline into a user-friendly, multi-platform, and freely available software. To validate our approach, we generated 3D statistical maps of endomembrane compartments at subcellular resolution within an average epidermal root cell from collections of image stacks. This revealed unsuspected polar distribution patterns of organelles that were not detectable in individual images. By reversing the classical 'measure-then-average' paradigm, one major benefit of the proposed strategy is the production and display of statistical 3D representations of spatial organizations, thus fully preserving the spatial dimension of image data and at the same time allowing their integration over individual observations. The approach and software are generic and should be of general interest for experimental and modeling studies of spatial organizations at multiple scales (subcellular, cellular, tissular) in biological systems.

  1. The three-dimensional elemental distribution based on the surface topography by confocal 3D-XRF analysis

    NASA Astrophysics Data System (ADS)

    Yi, Longtao; Qin, Min; Wang, Kai; Lin, Xue; Peng, Shiqi; Sun, Tianxi; Liu, Zhiguo

    2016-09-01

    Confocal three-dimensional micro-X-ray fluorescence (3D-XRF) is a good surface analysis technology widely used to analyse elements and elemental distributions. However, it has rarely been applied to analyse surface topography and 3D elemental mapping in surface morphology. In this study, a surface adaptive algorithm using the progressive approximation method was designed to obtain surface topography. A series of 3D elemental mapping analyses in surface morphology were performed in laboratories to analyse painted pottery fragments from the Majiayao Culture (3300-2900 BC). To the best of our knowledge, for the first time, sample surface topography and 3D elemental mapping were simultaneously obtained. Besides, component and depth analyses were also performed using synchrotron radiation confocal 3D-XRF and tabletop confocal 3D-XRF, respectively. The depth profiles showed that the sample has a layered structure. The 3D elemental mapping showed that the red pigment, black pigment, and pottery coat contain a large amount of Fe, Mn, and Ca, respectively. From the 3D elemental mapping analyses at different depths, a 3D rendering was obtained, clearly showing the 3D distributions of the red pigment, black pigment, and pottery coat. Compared with conventional 3D scanning, this method is time-efficient for analysing 3D elemental distributions and hence especially suitable for samples with non-flat surfaces.

  2. Integrating Data Clustering and Visualization for the Analysis of 3D Gene Expression Data

    SciTech Connect

    Data Analysis and Visualization and the Department of Computer Science, University of California, Davis, One Shields Avenue, Davis CA 95616, USA,; nternational Research Training Group ``Visualization of Large and Unstructured Data Sets,'' University of Kaiserslautern, Germany; Computational Research Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA; Genomics Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley CA 94720, USA; Life Sciences Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley CA 94720, USA,; Computer Science Division,University of California, Berkeley, CA, USA,; Computer Science Department, University of California, Irvine, CA, USA,; All authors are with the Berkeley Drosophila Transcription Network Project, Lawrence Berkeley National Laboratory,; Rubel, Oliver; Weber, Gunther H.; Huang, Min-Yu; Bethel, E. Wes; Biggin, Mark D.; Fowlkes, Charless C.; Hendriks, Cris L. Luengo; Keranen, Soile V. E.; Eisen, Michael B.; Knowles, David W.; Malik, Jitendra; Hagen, Hans; Hamann, Bernd

    2008-05-12

    The recent development of methods for extracting precise measurements of spatial gene expression patterns from three-dimensional (3D) image data opens the way for new analyses of the complex gene regulatory networks controlling animal development. We present an integrated visualization and analysis framework that supports user-guided data clustering to aid exploration of these new complex datasets. The interplay of data visualization and clustering-based data classification leads to improved visualization and enables a more detailed analysis than previously possible. We discuss (i) integration of data clustering and visualization into one framework; (ii) application of data clustering to 3D gene expression data; (iii) evaluation of the number of clusters k in the context of 3D gene expression clustering; and (iv) improvement of overall analysis quality via dedicated post-processing of clustering results based on visualization. We discuss the use of this framework to objectively define spatial pattern boundaries and temporal profiles of genes and to analyze how mRNA patterns are controlled by their regulatory transcription factors.

  3. Application of 3D Spatio-Temporal Data Modeling, Management, and Analysis in DB4GEO

    NASA Astrophysics Data System (ADS)

    Kuper, P. V.; Breunig, M.; Al-Doori, M.; Thomsen, A.

    2016-10-01

    Many of todaýs world wide challenges such as climate change, water supply and transport systems in cities or movements of crowds need spatio-temporal data to be examined in detail. Thus the number of examinations in 3D space dealing with geospatial objects moving in space and time or even changing their shapes in time will rapidly increase in the future. Prominent spatio-temporal applications are subsurface reservoir modeling, water supply after seawater desalination and the development of transport systems in mega cities. All of these applications generate large spatio-temporal data sets. However, the modeling, management and analysis of 3D geo-objects with changing shape and attributes in time still is a challenge for geospatial database architectures. In this article we describe the application of concepts for the modeling, management and analysis of 2.5D and 3D spatial plus 1D temporal objects implemented in DB4GeO, our service-oriented geospatial database architecture. An example application with spatio-temporal data of a landfill, near the city of Osnabrück in Germany demonstrates the usage of the concepts. Finally, an outlook on our future research focusing on new applications with big data analysis in three spatial plus one temporal dimension in the United Arab Emirates, especially the Dubai area, is given.

  4. Performance analysis of high quality parallel preconditioners applied to 3D finite element structural analysis

    SciTech Connect

    Kolotilina, L.; Nikishin, A.; Yeremin, A.

    1994-12-31

    The solution of large systems of linear equations is a crucial bottleneck when performing 3D finite element analysis of structures. Also, in many cases the reliability and robustness of iterative solution strategies, and their efficiency when exploiting hardware resources, fully determine the scope of industrial applications which can be solved on a particular computer platform. This is especially true for modern vector/parallel supercomputers with large vector length and for modern massively parallel supercomputers. Preconditioned iterative methods have been successfully applied to industrial class finite element analysis of structures. The construction and application of high quality preconditioners constitutes a high percentage of the total solution time. Parallel implementation of high quality preconditioners on such architectures is a formidable challenge. Two common types of existing preconditioners are the implicit preconditioners and the explicit preconditioners. The implicit preconditioners (e.g. incomplete factorizations of several types) are generally high quality but require solution of lower and upper triangular systems of equations per iteration which are difficult to parallelize without deteriorating the convergence rate. The explicit type of preconditionings (e.g. polynomial preconditioners or Jacobi-like preconditioners) require sparse matrix-vector multiplications and can be parallelized but their preconditioning qualities are less than desirable. The authors present results of numerical experiments with Factorized Sparse Approximate Inverses (FSAI) for symmetric positive definite linear systems. These are high quality preconditioners that possess a large resource of parallelism by construction without increasing the serial complexity.

  5. Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) for a 3-D Flexible Wing

    NASA Technical Reports Server (NTRS)

    Gumbert, Clyde R.; Hou, Gene J.-W.; Newman, Perry A.

    2001-01-01

    The formulation and implementation of an optimization method called Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) are extended from single discipline analysis (aerodynamics only) to multidisciplinary analysis - in this case, static aero-structural analysis and applied to a simple 3-D wing problem. The method aims to reduce the computational expense incurred in performing shape optimization using state-of-the-art Computational Fluid Dynamics (CFD) flow analysis, Finite Element Method (FEM) structural analysis and sensitivity analysis tools. Results for this small problem show that the method reaches the same local optimum as conventional optimization. However, unlike its application to the rigid wing (single discipline analysis), the method, as implemented here, may not show significant reduction in the computational cost. Similar reductions were seen in the two-design-variable (DV) problem results but not in the 8-DV results given here.

  6. Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) for a 3-D Flexible Wing

    NASA Technical Reports Server (NTRS)

    Gumbert, Clyde R.; Hou, Gene J.-W.

    2001-01-01

    The formulation and implementation of an optimization method called Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) are extended from single discipline analysis (aerodynamics only) to multidisciplinary analysis - in this case, static aero-structural analysis - and applied to a simple 3-D wing problem. The method aims to reduce the computational expense incurred in performing shape optimization using state-of-the-art Computational Fluid Dynamics (CFD) flow analysis, Finite Element Method (FEM) structural analysis and sensitivity analysis tools. Results for this small problem show that the method reaches the same local optimum as conventional optimization. However, unlike its application to the win,, (single discipline analysis), the method. as I implemented here, may not show significant reduction in the computational cost. Similar reductions were seen in the two-design-variable (DV) problem results but not in the 8-DV results given here.

  7. A Generalized Approach to the Modeling and Analysis of 3D Surface Morphology in Organisms

    PubMed Central

    Pappas, Janice L.; Miller, Daniel J.

    2013-01-01

    The surface geometry of an organism represents the boundary of its three-dimensional (3D) form and can be used as a proxy for the phenotype. A mathematical approach is presented that describes surface morphology using parametric 3D equations with variables expressed as x, y, z in terms of parameters u, v. Partial differentiation of variables with respect to parameters yields elements of the Jacobian representing tangent lines and planes of every point on the surface. Jacobian elements provide a compact size-free summary of the entire surface, and can be used as variables in principal components analysis to produce a morphospace. Mollusk and echinoid models are generated to demonstrate that whole organisms can be represented in a common morphospace, regardless of differences in size, geometry, and taxonomic affinity. Models can be used to simulate theoretical forms, novel morphologies, and patterns of phenotypic variation, and can also be empirically-based by designing them with reference to actual forms using reverse engineering principles. Although this study uses the Jacobian to summarize models, they can also be analyzed with 3D methods such as eigensurface, spherical harmonics, wavelet analysis, and geometric morphometrics. This general approach should prove useful for exploring broad questions regarding morphological evolution and variation. PMID:24204866

  8. A stabilized complementarity formulation for nonlinear analysis of 3D bimodular materials

    NASA Astrophysics Data System (ADS)

    Zhang, L.; Zhang, H. W.; Wu, J.; Yan, B.

    2016-06-01

    Bi-modulus materials with different mechanical responses in tension and compression are often found in civil, composite, and biological engineering. Numerical analysis of bimodular materials is strongly nonlinear and convergence is usually a problem for traditional iterative schemes. This paper aims to develop a stabilized computational method for nonlinear analysis of 3D bimodular materials. Based on the parametric variational principle, a unified constitutive equation of 3D bimodular materials is proposed, which allows the eight principal stress states to be indicated by three parametric variables introduced in the principal stress directions. The original problem is transformed into a standard linear complementarity problem (LCP) by the parametric virtual work principle and a quadratic programming algorithm is developed by solving the LCP with the classic Lemke's algorithm. Update of elasticity and stiffness matrices is avoided and, thus, the proposed algorithm shows an excellent convergence behavior compared with traditional iterative schemes. Numerical examples show that the proposed method is valid and can accurately analyze mechanical responses of 3D bimodular materials. Also, stability of the algorithm is greatly improved.

  9. The 3-D Navier-Stokes analysis of crossing, glancing shocks/turbulent boundary layer interactions

    NASA Technical Reports Server (NTRS)

    Reddy, D. R.

    1991-01-01

    Three dimensional viscous flow analysis is performed for a configuration where two crossing and glancing shocks interact with a turbulent boundary layer. A time marching 3-D full Navier-Stokes code, called PARC3D, is used to compute the flow field, and the solution is compared to the experimental data obtained at the NASA Lewis Research Center's 1 x 1 ft supersonic wind tunnel facility. The study is carried out as part of the continuing code assessment program in support of the generic hypersonic research at NASA Lewis. Detailed comparisons of static pressure fields and oil flow patterns are made with the corresponding solution on the wall containing the shock/boundary layer interaction in an effort to validate the code for hypersonic inlet applications.

  10. 3-D Navier-Stokes analysis of crossing, glancing shocks/turbulent boundary layer interactions

    NASA Technical Reports Server (NTRS)

    Reddy, D. R.

    1991-01-01

    Three dimensional viscous flow analysis is performed for a configuration where two crossing and glancing shocks interact with a turbulent boundary layer. A time marching 3-D full Navier-Stokes code, called PARC3D, is used to compute the flow field, and the solution is compared to the experimental data obtained at the NASA Lewis Research Center's 1 x 1 ft supersonic wind tunnel facility. The study is carried out as part of the continuing code assessment program in support of the generic hypersonic research at NASA Lewis. Detailed comparisons of static pressure fields and oil flow patterns are made with the corresponding solution on the wall containing the shock/boundary layer interaction in an effort to validate the code for hypersonic inlet applications.

  11. Spatio-temporal registration in multiplane MRI acquisitions for 3D colon motiliy analysis

    NASA Astrophysics Data System (ADS)

    Kutter, Oliver; Kirchhoff, Sonja; Berkovich, Marina; Reiser, Maximilian; Navab, Nassir

    2008-03-01

    In this paper we present a novel method for analyzing and visualizing dynamic peristaltic motion of the colon in 3D from two series of differently oriented 2D MRI images. To this end, we have defined an MRI examination protocol, and introduced methods for spatio-temporal alignment of the two MRI image series into a common reference. This represents the main contribution of this paper, which enables the 3D analysis of peristaltic motion. The objective is to provide a detailed insight into this complex motion, aiding in the diagnosis and characterization of colon motion disorders. We have applied the proposed spatio-temporal method on Cine MRI data sets of healthy volunteers. The results have been inspected and validated by an expert radiologist. Segmentation and cylindrical approximation of the colon results in a 4D visualization of the peristaltic motion.

  12. Mechanical performance and parameter sensitivity analysis of 3D braided composites joints.

    PubMed

    Wu, Yue; Nan, Bo; Chen, Liang

    2014-01-01

    3D braided composite joints are the important components in CFRP truss, which have significant influence on the reliability and lightweight of structures. To investigate the mechanical performance of 3D braided composite joints, a numerical method based on the microscopic mechanics is put forward, the modeling technologies, including the material constants selection, element type, grid size, and the boundary conditions, are discussed in detail. Secondly, a method for determination of ultimate bearing capacity is established, which can consider the strength failure. Finally, the effect of load parameters, geometric parameters, and process parameters on the ultimate bearing capacity of joints is analyzed by the global sensitivity analysis method. The results show that the main pipe diameter thickness ratio γ, the main pipe diameter D, and the braided angle α are sensitive to the ultimate bearing capacity N.

  13. Mechanical Performance and Parameter Sensitivity Analysis of 3D Braided Composites Joints

    PubMed Central

    Wu, Yue; Nan, Bo; Chen, Liang

    2014-01-01

    3D braided composite joints are the important components in CFRP truss, which have significant influence on the reliability and lightweight of structures. To investigate the mechanical performance of 3D braided composite joints, a numerical method based on the microscopic mechanics is put forward, the modeling technologies, including the material constants selection, element type, grid size, and the boundary conditions, are discussed in detail. Secondly, a method for determination of ultimate bearing capacity is established, which can consider the strength failure. Finally, the effect of load parameters, geometric parameters, and process parameters on the ultimate bearing capacity of joints is analyzed by the global sensitivity analysis method. The results show that the main pipe diameter thickness ratio γ, the main pipe diameter D, and the braided angle α are sensitive to the ultimate bearing capacity N. PMID:25121121

  14. Finite Element Analysis of Meniscal Anatomical 3D Scaffolds: Implications for Tissue Engineering

    PubMed Central

    Moroni, L; Lambers, F.M; Wilson, W; van Donkelaar, C.C; de Wijn, JR; Huiskesb, R; van Blitterswijk, C.A

    2007-01-01

    Solid Free-Form Fabrication (SFF) technologies allow the fabrication of anatomical 3D scaffolds from computer tomography (CT) or magnetic resonance imaging (MRI) patients’ dataset. These structures can be designed and fabricated with a variable, interconnected and accessible porous network, resulting in modulable mechanical properties, permeability, and architecture that can be tailored to mimic a specific tissue to replace or regenerate. In this study, we evaluated whether anatomical meniscal 3D scaffolds with matching mechanical properties and architecture are beneficial for meniscus replacement as compared to meniscectomy. After acquiring CT and MRI of porcine menisci, 3D fiber-deposited (3DF) scaffolds were fabricated with different architectures by varying the deposition pattern of the fibers comprising the final structure. The mechanical behaviour of 3DF scaffolds with different architectures and of porcine menisci was measured by static and dynamic mechanical analysis and the effect of these tissue engineering templates on articular cartilage was assessed by finite element analysis (FEA) and compared to healthy conditions or to meniscectomy. Results show that 3DF anatomical menisci scaffolds can be fabricated with pore different architectures and with mechanical properties matching those of natural menisci. FEA predicted a beneficial effect of meniscus replacement with 3D scaffolds in different mechanical loading conditions as compared to meniscectomy. No influence of the internal scaffold architecture was found on articular cartilage damage. Although FEA predictions should be further confirmed by in vitro and in vivo experiments, this study highlights meniscus replacement by SFF anatomical scaffolds as a potential alternative to meniscectomy. PMID:19662124

  15. 3D structure tensor analysis of light microscopy data for validating diffusion MRI.

    PubMed

    Khan, Ahmad Raza; Cornea, Anda; Leigland, Lindsey A; Kohama, Steven G; Jespersen, Sune Nørhøj; Kroenke, Christopher D

    2015-05-01

    Diffusion magnetic resonance imaging (d-MRI) is a powerful non-invasive and non-destructive technique for characterizing brain tissue on the microscopic scale. However, the lack of validation of d-MRI by independent experimental means poses an obstacle to accurate interpretation of data acquired using this method. Recently, structure tensor analysis has been applied to light microscopy images, and this technique holds promise to be a powerful validation strategy for d-MRI. Advantages of this approach include its similarity to d-MRI in terms of averaging the effects of a large number of cellular structures, and its simplicity, which enables it to be implemented in a high-throughput manner. However, a drawback of previous implementations of this technique arises from it being restricted to 2D. As a result, structure tensor analyses have been limited to tissue sectioned in a direction orthogonal to the direction of interest. Here we describe the analytical framework for extending structure tensor analysis to 3D, and utilize the results to analyze serial image "stacks" acquired with confocal microscopy of rhesus macaque hippocampal tissue. Implementation of 3D structure tensor procedures requires removal of sources of anisotropy introduced in tissue preparation and confocal imaging. This is accomplished with image processing steps to mitigate the effects of anisotropic tissue shrinkage, and the effects of anisotropy in the point spread function (PSF). In order to address the latter confound, we describe procedures for measuring the dependence of PSF anisotropy on distance from the microscope objective within tissue. Prior to microscopy, ex vivo d-MRI measurements performed on the hippocampal tissue revealed three regions of tissue with mutually orthogonal directions of least restricted diffusion that correspond to CA1, alveus and inferior longitudinal fasciculus. We demonstrate the ability of 3D structure tensor analysis to identify structure tensor orientations that

  16. 3D structure tensor analysis of light microscopy data for validating diffusion MRI

    PubMed Central

    Khan, Ahmad Raza; Cornea, Anda; Leigland, Lindsey A.; Kohama, Steven G.; Jespersen, Sune Nørhøj; Kroenke, Christopher D.

    2015-01-01

    Diffusion magnetic resonance imaging (d-MRI) is a powerful non-invasive and non-destructive technique for characterizing brain tissue on the microscopic scale. However, the lack of validation of d-MRI by independent experimental means poses an obstacle to accurate interpretation of data acquired using this method. Recently, structure tensor analysis has been applied to light microscopy images, and this technique holds promise to be a powerful validation strategy for d-MRI. Advantages of this approach include its similarity to d-MRI in terms of averaging the effects of a large number of cellular structures, and its simplicity, which enables it to be implemented in a high-throughput manner. However, a drawback of previous implementations of this technique arises from it being restricted to 2D. As a result, structure tensor analyses have been limited to tissue sectioned in a direction orthogonal to the direction of interest. Here we describe the analytical framework for extending structure tensor analysis to 3D, and utilize the results to analyze serial image “stacks” acquired with confocal microscopy of rhesus macaque hippocampal tissue. Implementation of 3D structure tensor procedures requires removal of sources of anisotropy introduced in tissue preparation and confocal imaging. This is accomplished with image processing steps to mitigate the effects of anisotropic tissue shrinkage, and the effects of anisotropy in the point spread function (PSF). In order to address the latter confound, we describe procedures for measuring the dependence of PSF anisotropy on distance from the microscope objective within tissue. Prior to microscopy, ex vivo d-MRI measurements performed on the hippocampal tissue revealed three regions of tissue with mutually orthogonal directions of least restricted diffusion that correspond to CA1, alveus and inferior longitudinal fasciculus. We demonstrate the ability of 3D structure tensor analysis to identify structure tensor orientations

  17. Application of 3D eddy current analysis on magnetically levitated vehicles

    SciTech Connect

    Fukumoto, H.; Kameoka, Y.; Yoshioka, K.; Takizawa, T.; Kobayashi, T. )

    1993-03-01

    The eddy currents induced on the superconducting magnet (SCM) vessels of magnetically levitated vehicles (MAGLEV) have been analyzed. A 3D eddy current analysis code, based on a finite element method with thin shell approximation, is developed and verified through a mock-up SCM experiment. Through a coupled electromagnetic and mechanical analysis under SCM vibration, a SCM structure with low resistivity material coating on the inner vessel of SCM is found to be suitable for the significant reduction of helium evaporation due to eddy current loss.

  18. On 3-D inelastic analysis methods for hot section components (base program)

    NASA Technical Reports Server (NTRS)

    Wilson, R. B.; Bak, M. J.; Nakazawa, S.; Banerjee, P. K.

    1986-01-01

    A 3-D Inelastic Analysis Method program is described. This program consists of a series of new computer codes embodying a progression of mathematical models (mechanics of materials, special finite element, boundary element) for streamlined analysis of: (1) combustor liners, (2) turbine blades, and (3) turbine vanes. These models address the effects of high temperatures and thermal/mechanical loadings on the local (stress/strain)and global (dynamics, buckling) structural behavior of the three selected components. Three computer codes, referred to as MOMM (Mechanics of Materials Model), MHOST (Marc-Hot Section Technology), and BEST (Boundary Element Stress Technology), have been developed and are briefly described in this report.

  19. Metabolic biotransformation half-lives in fish: QSAR modeling and consensus analysis.

    PubMed

    Papa, Ester; van der Wal, Leon; Arnot, Jon A; Gramatica, Paola

    2014-02-01

    Bioaccumulation in fish is a function of competing rates of chemical uptake and elimination. For hydrophobic organic chemicals bioconcentration, bioaccumulation and biomagnification potential are high and the biotransformation rate constant is a key parameter. Few measured biotransformation rate constant data are available compared to the number of chemicals that are being evaluated for bioaccumulation hazard and for exposure and risk assessment. Three new Quantitative Structure-Activity Relationships (QSARs) for predicting whole body biotransformation half-lives (HLN) in fish were developed and validated using theoretical molecular descriptors that seek to capture structural characteristics of the whole molecule and three data set splitting schemes. The new QSARs were developed using a minimal number of theoretical descriptors (n=9) and compared to existing QSARs developed using fragment contribution methods that include up to 59 descriptors. The predictive statistics of the models are similar thus further corroborating the predictive performance of the different QSARs; Q(2)ext ranges from 0.75 to 0.77, CCCext ranges from 0.86 to 0.87, RMSE in prediction ranges from 0.56 to 0.58. The new QSARs provide additional mechanistic insights into the biotransformation capacity of organic chemicals in fish by including whole molecule descriptors and they also include information on the domain of applicability for the chemical of interest. Advantages of consensus modeling for improving overall prediction and minimizing false negative errors in chemical screening assessments, for identifying potential sources of residual error in the empirical HLN database, and for identifying structural features that are not well represented in the HLN dataset to prioritize future testing needs are illustrated.

  20. Human factors flight trial analysis for 2D/3D SVS

    NASA Astrophysics Data System (ADS)

    Schiefele, Jens; Howland, Duncan; Maris, John; Wipplinger, Patrick

    2004-08-01

    The paper describes flight trials performed in Reno, NV. Flight trial were conducted with a Cheyenne 1 from Marinvent. Twelve pilots flew the Cheyenne in seventy-two approaches to the Reno airfield. All pilots flew completely andomized settings. Three different settings (standard displays, 2D moving map, and 2D/3D moving map) were evaluated. They included seamless evaluation for STAR, approach, and taxi operations. The flight trial goal was to evaluate the objective performance of pilots compared among the different settings. As dependent variables, positional and time accuracy were measured. Analysis was conducted by an ANOVA test. In parallel, all pilots answered subjective Cooper-Harper, situation awareness rating technique (SART), situational awareness probe (SAP), and questionnaires.This article describes the human factor analysis from flight trials performed in Reno, NV. Flight trials were conducted with a Cheyenne 1 from Marinvent. Thirteen pilots flew the Cheyenne in seventy-two approaches to the Reno airfield. All pilots flew completely randomized settings. Three different display configurations: Elec. Flight Information System (EFIS), EFIS and 2D moving map, and 3D SVS Primary Flight Display (PFD) and 2D moving map were evaluated. They included normal/abnormal procedure evaluation for: Steep turns and reversals, Unusual attitude recovery, Radar vector guidance towards terrain, Non-precision approaches, En-route alternate for non-IFR rated pilots encountering IMC, and Taxiing on complex taxi-routes. The flight trial goal was to evaluate the objective performance of pilots for the different display configurations. As dependent variables, positional and time data were measured. Analysis was performed by an ANOVA test. In parallel, all pilots answered subjective NASA Task Load Index, Cooper-Harper, Situation Awareness Rating Technique (SART), and questionnaires. The result shows that pilots flying 2D/3D SVS perform no worse than pilots with conventional

  1. Action Sport Cameras as an Instrument to Perform a 3D Underwater Motion Analysis.

    PubMed

    Bernardina, Gustavo R D; Cerveri, Pietro; Barros, Ricardo M L; Marins, João C B; Silvatti, Amanda P

    2016-01-01

    Action sport cameras (ASC) are currently adopted mainly for entertainment purposes but their uninterrupted technical improvements, in correspondence of cost decreases, are going to disclose them for three-dimensional (3D) motion analysis in sport gesture study and athletic performance evaluation quantitatively. Extending this technology to sport analysis however still requires a methodologic step-forward to making ASC a metric system, encompassing ad-hoc camera setup, image processing, feature tracking, calibration and 3D reconstruction. Despite traditional laboratory analysis, such requirements become an issue when coping with both indoor and outdoor motion acquisitions of athletes. In swimming analysis for example, the camera setup and the calibration protocol are particularly demanding since land and underwater cameras are mandatory. In particular, the underwater camera calibration can be an issue affecting the reconstruction accuracy. In this paper, the aim is to evaluate the feasibility of ASC for 3D underwater analysis by focusing on camera setup and data acquisition protocols. Two GoPro Hero3+ Black (frequency: 60Hz; image resolutions: 1280×720/1920×1080 pixels) were located underwater into a swimming pool, surveying a working volume of about 6m3. A two-step custom calibration procedure, consisting in the acquisition of one static triad and one moving wand, carrying nine and one spherical passive markers, respectively, was implemented. After assessing camera parameters, a rigid bar, carrying two markers at known distance, was acquired in several positions within the working volume. The average error upon the reconstructed inter-marker distances was less than 2.5mm (1280×720) and 1.5mm (1920×1080). The results of this study demonstrate that the calibration of underwater ASC is feasible enabling quantitative kinematic measurements with accuracy comparable to traditional motion capture systems. PMID:27513846

  2. Action Sport Cameras as an Instrument to Perform a 3D Underwater Motion Analysis

    PubMed Central

    Cerveri, Pietro; Barros, Ricardo M. L.; Marins, João C. B.; Silvatti, Amanda P.

    2016-01-01

    Action sport cameras (ASC) are currently adopted mainly for entertainment purposes but their uninterrupted technical improvements, in correspondence of cost decreases, are going to disclose them for three-dimensional (3D) motion analysis in sport gesture study and athletic performance evaluation quantitatively. Extending this technology to sport analysis however still requires a methodologic step-forward to making ASC a metric system, encompassing ad-hoc camera setup, image processing, feature tracking, calibration and 3D reconstruction. Despite traditional laboratory analysis, such requirements become an issue when coping with both indoor and outdoor motion acquisitions of athletes. In swimming analysis for example, the camera setup and the calibration protocol are particularly demanding since land and underwater cameras are mandatory. In particular, the underwater camera calibration can be an issue affecting the reconstruction accuracy. In this paper, the aim is to evaluate the feasibility of ASC for 3D underwater analysis by focusing on camera setup and data acquisition protocols. Two GoPro Hero3+ Black (frequency: 60Hz; image resolutions: 1280×720/1920×1080 pixels) were located underwater into a swimming pool, surveying a working volume of about 6m3. A two-step custom calibration procedure, consisting in the acquisition of one static triad and one moving wand, carrying nine and one spherical passive markers, respectively, was implemented. After assessing camera parameters, a rigid bar, carrying two markers at known distance, was acquired in several positions within the working volume. The average error upon the reconstructed inter-marker distances was less than 2.5mm (1280×720) and 1.5mm (1920×1080). The results of this study demonstrate that the calibration of underwater ASC is feasible enabling quantitative kinematic measurements with accuracy comparable to traditional motion capture systems. PMID:27513846

  3. Action Sport Cameras as an Instrument to Perform a 3D Underwater Motion Analysis.

    PubMed

    Bernardina, Gustavo R D; Cerveri, Pietro; Barros, Ricardo M L; Marins, João C B; Silvatti, Amanda P

    2016-01-01

    Action sport cameras (ASC) are currently adopted mainly for entertainment purposes but their uninterrupted technical improvements, in correspondence of cost decreases, are going to disclose them for three-dimensional (3D) motion analysis in sport gesture study and athletic performance evaluation quantitatively. Extending this technology to sport analysis however still requires a methodologic step-forward to making ASC a metric system, encompassing ad-hoc camera setup, image processing, feature tracking, calibration and 3D reconstruction. Despite traditional laboratory analysis, such requirements become an issue when coping with both indoor and outdoor motion acquisitions of athletes. In swimming analysis for example, the camera setup and the calibration protocol are particularly demanding since land and underwater cameras are mandatory. In particular, the underwater camera calibration can be an issue affecting the reconstruction accuracy. In this paper, the aim is to evaluate the feasibility of ASC for 3D underwater analysis by focusing on camera setup and data acquisition protocols. Two GoPro Hero3+ Black (frequency: 60Hz; image resolutions: 1280×720/1920×1080 pixels) were located underwater into a swimming pool, surveying a working volume of about 6m3. A two-step custom calibration procedure, consisting in the acquisition of one static triad and one moving wand, carrying nine and one spherical passive markers, respectively, was implemented. After assessing camera parameters, a rigid bar, carrying two markers at known distance, was acquired in several positions within the working volume. The average error upon the reconstructed inter-marker distances was less than 2.5mm (1280×720) and 1.5mm (1920×1080). The results of this study demonstrate that the calibration of underwater ASC is feasible enabling quantitative kinematic measurements with accuracy comparable to traditional motion capture systems.

  4. Comparing Facial 3D Analysis With DNA Testing to Determine Zygosities of Twins.

    PubMed

    Vuollo, Ville; Sidlauskas, Mantas; Sidlauskas, Antanas; Harila, Virpi; Salomskiene, Loreta; Zhurov, Alexei; Holmström, Lasse; Pirttiniemi, Pertti; Heikkinen, Tuomo

    2015-06-01

    The aim of this study was to compare facial 3D analysis to DNA testing in twin zygosity determinations. Facial 3D images of 106 pairs of young adult Lithuanian twins were taken with a stereophotogrammetric device (3dMD, Atlanta, Georgia) and zygosity was determined according to similarity of facial form. Statistical pattern recognition methodology was used for classification. The results showed that in 75% to 90% of the cases, zygosity determinations were similar to DNA-based results. There were 81 different classification scenarios, including 3 groups, 3 features, 3 different scaling methods, and 3 threshold levels. It appeared that coincidence with 0.5 mm tolerance is the most suitable feature for classification. Also, leaving out scaling improves results in most cases. Scaling was expected to equalize the magnitude of differences and therefore lead to better recognition performance. Still, better classification features and a more effective scaling method or classification in different facial areas could further improve the results. In most of the cases, male pair zygosity recognition was at a higher level compared with females. Erroneously classified twin pairs appear to be obvious outliers in the sample. In particular, faces of young dizygotic (DZ) twins may be so similar that it is very hard to define a feature that would help classify the pair as DZ. Correspondingly, monozygotic (MZ) twins may have faces with quite different shapes. Such anomalous twin pairs are interesting exceptions, but they form a considerable portion in both zygosity groups.

  5. Artificial neural networks for 3-D motion analysis-Part II: Nonrigid motion.

    PubMed

    Chen, T; Lin, W C; Chen, C T

    1995-01-01

    For pt. I see ibid., p. 1386-93 (1995). An approach applying artificial neural net techniques to 3D nonrigid motion analysis is proposed. The 3D nonrigid motion of the left ventricle of a human heart is examined using biplanar cineangiography data, consisting of 3D coordinates of 30 coronary artery bifurcation points of the left ventricle and the correspondences of these points taken over 10 time instants during the heart cardiac cycle. The motion is decomposed into global rigid motion and a set of local nonrigid deformations which are coupled with the global motion. The global rigid motion can be estimated precisely as a translation vecto and a rotation matrix. Local nonrigid deformation estimation is discussed. A set of neural nets similar in structure and dynamics but different in physical size is proposed to tackle the problem of nonrigidity. These neural networks are interconnected through feedbacks. The activation function of the output layer is selected so that a feedback is involved in the output updating. The constraints are specified to ensure stable and globally consistent estimation. The objective is to find the optimal deformation matrices that satisfy the constraints for all coronary artery bifurcation points of the left ventricle. The proposed neural networks differ from other existing neural network models in their unique structure and dynamics.

  6. A complete system for 3D reconstruction of roots for phenotypic analysis.

    PubMed

    Kumar, Pankaj; Cai, Jinhai; Miklavcic, Stanley J

    2015-01-01

    Here we present a complete system for 3D reconstruction of roots grown in a transparent gel medium or washed and suspended in water. The system is capable of being fully automated as it is self calibrating. The system starts with detection of root tips in root images from an image sequence generated by a turntable motion. Root tips are detected using the statistics of Zernike moments on image patches centred on high curvature points on root boundary and Bayes classification rule. The detected root tips are tracked in the image sequence using a multi-target tracking algorithm. Conics are fitted to the root tip trajectories using a novel ellipse fitting algorithm which weighs the data points by its eccentricity. The conics projected from the circular trajectory have a complex conjugate intersection which are image of the circular points. Circular points constraint the image of the absolute conics which are directly related to the internal parameters of the camera. The pose of the camera is computed from the image of the rotation axis and the horizon. The silhouettes of the roots and camera parameters are used to reconstruction the 3D voxel model of the roots. We show the results of real 3D reconstruction of roots which are detailed and realistic for phenotypic analysis. PMID:25381112

  7. 3D distribution of interstellar medium in the Galaxy: Preparation for analysis of Gaia observations

    SciTech Connect

    Puspitarini, Lucky; Lallement, Rosine

    2015-09-30

    Accurate and detailed three-dimensional (3D) maps of Galactic interstellar medium (ISM) are still lacking. One way to obtain such 3D descriptions is to record a large set of individual absorption or reddening measurements toward target stars located at various known distances and directions. The inversion of these measurements using a tomographic method can produce spatial distribution of the ISM. Until recently absorption data were very limited and distances to the target stars are still uncertain, but the situation will greatly improve thanks to current and future massive stellar surveys from ground, and to Gaia mission. To prepare absorption data for inversion from a huge number of stellar spectra, automated tools are needed. We have developed various spectral analysis tools adapted to different type of spectra, early- or late- type star. We also have used diffuse interstellar bands (DIBs) to trace IS structures and kinematics. Although we do not know yet their carriers, they can be a promising tool to trace distant interstellar clouds or Galactic arms. We present some examples of the interstellar fitting and show the potentiality of DIBs in tracing the ISM. We will also briefly show and comment the latest 3D map of the local ISM which reveal nearby cloud complexes and cavities.

  8. 3D imaging for ballistics analysis using chromatic white light sensor

    NASA Astrophysics Data System (ADS)

    Makrushin, Andrey; Hildebrandt, Mario; Dittmann, Jana; Clausing, Eric; Fischer, Robert; Vielhauer, Claus

    2012-03-01

    The novel application of sensing technology, based on chromatic white light (CWL), gives a new insight into ballistic analysis of cartridge cases. The CWL sensor uses a beam of white light to acquire highly detailed topography and luminance data simultaneously. The proposed 3D imaging system combines advantages of 3D and 2D image processing algorithms in order to automate the extraction of firearm specific toolmarks shaped on fired specimens. The most important characteristics of a fired cartridge case are the type of the breech face marking as well as size, shape and location of extractor, ejector and firing pin marks. The feature extraction algorithm normalizes the casing surface and consistently searches for the appropriate distortions on the rim and on the primer. The location of the firing pin mark in relation to the lateral scratches on the rim provides unique rotation invariant characteristics of the firearm mechanisms. Additional characteristics are the volume and shape of the firing pin mark. The experimental evaluation relies on the data set of 15 cartridge cases fired from three 9mm firearms of different manufacturers. The results show very high potential of 3D imaging systems for casing-based computer-aided firearm identification, which is prospectively going to support human expertise.

  9. Reconstruction Accuracy Assessment of Surface and Underwater 3D Motion Analysis: A New Approach.

    PubMed

    de Jesus, Kelly; de Jesus, Karla; Figueiredo, Pedro; Vilas-Boas, João Paulo; Fernandes, Ricardo Jorge; Machado, Leandro José

    2015-01-01

    This study assessed accuracy of surface and underwater 3D reconstruction of a calibration volume with and without homography. A calibration volume (6000 × 2000 × 2500 mm) with 236 markers (64 above and 88 underwater control points--with 8 common points at water surface--and 92 validation points) was positioned on a 25 m swimming pool and recorded with two surface and four underwater cameras. Planar homography estimation for each calibration plane was computed to perform image rectification. Direct linear transformation algorithm for 3D reconstruction was applied, using 1600000 different combinations of 32 and 44 points out of the 64 and 88 control points for surface and underwater markers (resp.). Root Mean Square (RMS) error with homography of control and validations points was lower than without it for surface and underwater cameras (P ≤ 0.03). With homography, RMS errors of control and validation points were similar between surface and underwater cameras (P ≥ 0.47). Without homography, RMS error of control points was greater for underwater than surface cameras (P ≤ 0.04) and the opposite was observed for validation points (P ≤ 0.04). It is recommended that future studies using 3D reconstruction should include homography to improve swimming movement analysis accuracy.

  10. Spacecraft charging analysis with the implicit particle-in-cell code iPic3D

    SciTech Connect

    Deca, J.; Lapenta, G.; Marchand, R.; Markidis, S.

    2013-10-15

    We present the first results on the analysis of spacecraft charging with the implicit particle-in-cell code iPic3D, designed for running on massively parallel supercomputers. The numerical algorithm is presented, highlighting the implementation of the electrostatic solver and the immersed boundary algorithm; the latter which creates the possibility to handle complex spacecraft geometries. As a first step in the verification process, a comparison is made between the floating potential obtained with iPic3D and with Orbital Motion Limited theory for a spherical particle in a uniform stationary plasma. Second, the numerical model is verified for a CubeSat benchmark by comparing simulation results with those of PTetra for space environment conditions with increasing levels of complexity. In particular, we consider spacecraft charging from plasma particle collection, photoelectron and secondary electron emission. The influence of a background magnetic field on the floating potential profile near the spacecraft is also considered. Although the numerical approaches in iPic3D and PTetra are rather different, good agreement is found between the two models, raising the level of confidence in both codes to predict and evaluate the complex plasma environment around spacecraft.

  11. Using articulated scene models for dynamic 3d scene analysis in vista spaces

    NASA Astrophysics Data System (ADS)

    Beuter, Niklas; Swadzba, Agnes; Kummert, Franz; Wachsmuth, Sven

    2010-09-01

    In this paper we describe an efficient but detailed new approach to analyze complex dynamic scenes directly in 3D. The arising information is important for mobile robots to solve tasks in the area of household robotics. In our work a mobile robot builds an articulated scene model by observing the environment in the visual field or rather in the so-called vista space. The articulated scene model consists of essential knowledge about the static background, about autonomously moving entities like humans or robots and finally, in contrast to existing approaches, information about articulated parts. These parts describe movable objects like chairs, doors or other tangible entities, which could be moved by an agent. The combination of the static scene, the self-moving entities and the movable objects in one articulated scene model enhances the calculation of each single part. The reconstruction process for parts of the static scene benefits from removal of the dynamic parts and in turn, the moving parts can be extracted more easily through the knowledge about the background. In our experiments we show, that the system delivers simultaneously an accurate static background model, moving persons and movable objects. This information of the articulated scene model enables a mobile robot to detect and keep track of interaction partners, to navigate safely through the environment and finally, to strengthen the interaction with the user through the knowledge about the 3D articulated objects and 3D scene analysis. [Figure not available: see fulltext.

  12. Dynamic analysis of radial force density in brushless DC motor using 3-D equivalent magnetic circuit network method

    SciTech Connect

    Hur, J.; Chun, Y.D.; Lee, J.; Hyun, D.S.

    1998-09-01

    The distribution of radial force density in brushless permanent magnet DC motor is not uniform in axial direction. The analysis of radial force density has to consider the 3-D shape of teeth and overhand, because the radial force density causes vibration and acts on the surface of teeth inconstantly. For the analysis, a new 3-D equivalent magnetic circuit network method is used to account the rotor movement without remesh. The radial force density is calculated and analyzed by Maxwell stress tensor and discrete Fourier transform (DFT) respectively. The results of 3-D equivalent magnetic circuit method have been compared with the results of 3-D FEM.

  13. Linear indices of the "molecular pseudograph's atom adjacency matrix": definition, significance-interpretation, and application to QSAR analysis of flavone derivatives as HIV-1 integrase inhibitors.

    PubMed

    Marrero-Ponce, Yovani

    2004-01-01

    This report describes a new set of molecular descriptors of relevance to QSAR/QSPR studies and drug design, atom linear indices fk(xi). These atomic level chemical descriptors are based on the calculation of linear maps on Rn[fk(xi): Rn--> Rn] in canonical basis. In this context, the kth power of the molecular pseudograph's atom adjacency matrix [Mk(G)] denotes the matrix of fk(xi) with respect to the canonical basis. In addition, a local-fragment (atom-type) formalism was developed. The kth atom-type linear indices are calculated by summing the kth atom linear indices of all atoms of the same atom type in the molecules. Moreover, total (whole-molecule) linear indices are also proposed. This descriptor is a linear functional (linear form) on Rn. That is, the kth total linear indices is a linear map from Rn to the scalar R[ fk(x): Rn --> R]. Thus, the kth total linear indices are calculated by summing the atom linear indices of all atoms in the molecule. The features of the kth total and local linear indices are illustrated by examples of various types of molecular structures, including chain-lengthening, branching, heteroatoms-content, and multiple bonds. Additionally, the linear independence of the local linear indices to other 0D, 1D, 2D, and 3D molecular descriptors is demonstrated by using principal component analysis for 42 very heterogeneous molecules. Much redundancy and overlapping was found among total linear indices and most of the other structural indices presently in use in the QSPR/QSAR practice. On the contrary, the information carried by atom-type linear indices was strikingly different from that codified in most of the 229 0D-3D molecular descriptors used in this study. It is concluded that the local linear indices are an independent indices containing important structural information to be used in QSPR/QSAR and drug design studies. In this sense, atom, atom-type, and total linear indices were used for the prediction of pIC50 values for the cleavage

  14. LEWICE3D/GlennHT Particle Analysis of the Honeywell Al502 Low Pressure Compressor

    NASA Technical Reports Server (NTRS)

    Bidwell, Colin S.; Rigby, David L.

    2015-01-01

    A flow and ice particle trajectory analysis was performed for the booster of the Honeywell AL502 engine. The analysis focused on two closely related conditions one of which produced a rollback and another which did not rollback during testing in the Propulsion Systems Lab at NASA Glenn Research Center. The flow analysis was generated using the NASA Glenn GlennHT flow solver and the particle analysis was generated using the NASA Glenn LEWICE3D v3.56 ice accretion software. The flow and particle analysis used a 3D steady flow, mixing plane approach to model the transport of flow and particles through the engine. The inflow conditions for the rollback case were: airspeed, 145 ms; static pressure, 33,373 Pa; static temperature, 253.3 K. The inflow conditions for the non-roll-back case were: airspeed, 153 ms; static pressure, 34,252 Pa; static temperature, 260.1 K. Both cases were subjected to an ice particle cloud with a median volume diameter of 24 microns, an ice water content of 2.0 gm3 and a relative humidity of 100 percent. The most significant difference between the rollback and non-rollback conditions was the inflow static temperature which was 6.8 K higher for the non-rollback case.

  15. Semi-automated 3D Leaf Reconstruction and Analysis of Trichome Patterning from Light Microscopic Images

    PubMed Central

    Schrader, Andrea; Hülskamp, Martin; Tresch, Achim

    2013-01-01

    Trichomes are leaf hairs that are formed by single cells on the leaf surface. They are known to be involved in pathogen resistance. Their patterning is considered to emerge from a field of initially equivalent cells through the action of a gene regulatory network involving trichome fate promoting and inhibiting factors. For a quantitative analysis of single and double mutants or the phenotypic variation of patterns in different ecotypes, it is imperative to statistically evaluate the pattern reliably on a large number of leaves. Here we present a method that enables the analysis of trichome patterns at early developmental leaf stages and the automatic analysis of various spatial parameters. We focus on the most challenging young leaf stages that require the analysis in three dimensions, as the leaves are typically not flat. Our software TrichEratops reconstructs 3D surface models from 2D stacks of conventional light-microscope pictures. It allows the GUI-based annotation of different stages of trichome development, which can be analyzed with respect to their spatial distribution to capture trichome patterning events. We show that 3D modeling removes biases of simpler 2D models and that novel trichome patterning features increase the sensitivity for inter-accession comparisons. PMID:23637587

  16. Semi-automated 3D leaf reconstruction and analysis of trichome patterning from light microscopic images.

    PubMed

    Failmezger, Henrik; Jaegle, Benjamin; Schrader, Andrea; Hülskamp, Martin; Tresch, Achim

    2013-04-01

    Trichomes are leaf hairs that are formed by single cells on the leaf surface. They are known to be involved in pathogen resistance. Their patterning is considered to emerge from a field of initially equivalent cells through the action of a gene regulatory network involving trichome fate promoting and inhibiting factors. For a quantitative analysis of single and double mutants or the phenotypic variation of patterns in different ecotypes, it is imperative to statistically evaluate the pattern reliably on a large number of leaves. Here we present a method that enables the analysis of trichome patterns at early developmental leaf stages and the automatic analysis of various spatial parameters. We focus on the most challenging young leaf stages that require the analysis in three dimensions, as the leaves are typically not flat. Our software TrichEratops reconstructs 3D surface models from 2D stacks of conventional light-microscope pictures. It allows the GUI-based annotation of different stages of trichome development, which can be analyzed with respect to their spatial distribution to capture trichome patterning events. We show that 3D modeling removes biases of simpler 2D models and that novel trichome patterning features increase the sensitivity for inter-accession comparisons.

  17. 3D visualisation and analysis of single and coalescing tracks in Solid state Nuclear Track Detectors

    NASA Astrophysics Data System (ADS)

    Wertheim, David; Gillmore, Gavin; Brown, Louise; Petford, Nick

    2010-05-01

    Exposure to radon gas (222Rn) and associated ionising decay products can cause lung cancer in humans (1). Solid state Nuclear Track Detectors (SSNTDs) can be used to monitor radon concentrations (2). Radon particles form tracks in the detectors and these tracks can be etched in order to enable 2D surface image analysis. We have previously shown that confocal microscopy can be used for 3D visualisation of etched SSNTDs (3). The aim of the study was to further investigate track angles and patterns in SSNTDs. A 'LEXT' confocal laser scanning microscope (Olympus Corporation, Japan) was used to acquire 3D image datasets of five CR-39 plastic SSNTD's. The resultant 3D visualisations were analysed by eye and inclination angles assessed on selected tracks. From visual assessment, single isolated tracks as well as coalescing tracks were observed on the etched detectors. In addition varying track inclination angles were observed. Several different patterns of track formation were seen such as single isolated and double coalescing tracks. The observed track angles of inclination may help to assess the angle at which alpha particles hit the detector. Darby, S et al. Radon in homes and risk of lung cancer : collaborative analysis of individual data from 13 European case-control studies. British Medical Journal 2005; 330, 223-226. Phillips, P.S., Denman, A.R., Crockett, R.G.M., Gillmore, G., Groves-Kirkby, C.J., Woolridge, A., Comparative Analysis of Weekly vs. Three monthly radon measurements in dwellings. DEFRA Report No., DEFRA/RAS/03.006. (2004). Wertheim D, Gillmore G, Brown L, and Petford N. A new method of imaging particle tracks in Solid State Nuclear Track Detectors. Journal of Microscopy 2010; 237: 1-6.

  18. 3-D inelastic analysis methods for hot section components. Volume 2: Advanced special functions models

    NASA Technical Reports Server (NTRS)

    Wilson, R. B.; Banerjee, P. K.

    1987-01-01

    This Annual Status Report presents the results of work performed during the third year of the 3-D Inelastic Analysis Methods for Hot Sections Components program (NASA Contract NAS3-23697). The objective of the program is to produce a series of computer codes that permit more accurate and efficient three-dimensional analyses of selected hot section components, i.e., combustor liners, turbine blades, and turbine vanes. The computer codes embody a progression of mathematical models and are streamlined to take advantage of geometrical features, loading conditions, and forms of material response that distinguish each group of selected components.

  19. CASMO5/TSUNAMI-3D spent nuclear fuel reactivity uncertainty analysis

    SciTech Connect

    Ferrer, R.; Rhodes, J.; Smith, K.

    2012-07-01

    The CASMO5 lattice physics code is used in conjunction with the TSUNAMI-3D sequence in ORNL's SCALE 6 code system to estimate the uncertainties in hot-to-cold reactivity changes due to cross-section uncertainty for PWR assemblies at various burnup points. The goal of the analysis is to establish the multiplication factor uncertainty similarity between various fuel assemblies at different conditions in a quantifiable manner and to obtain a bound on the hot-to-cold reactivity uncertainty over the various assembly types and burnup attributed to fundamental cross-section data uncertainty. (authors)

  20. Analysis of the Possibilities of Using Low-Cost Scanning System in 3d Modeling

    NASA Astrophysics Data System (ADS)

    Kedzierski, M.; Wierzbickia, D.; Fryskowska, A.; Chlebowska, B.

    2016-06-01

    The laser scanning technique is still a very popular and fast growing method of obtaining information on modeling 3D objects. The use of low-cost miniature scanners creates new opportunities for small objects of 3D modeling based on point clouds acquired from the scan. The same, the development of accuracy and methods of automatic processing of this data type is noticeable. The article presents methods of collecting raw datasets in the form of a point-cloud using a low-cost ground-based laser scanner FabScan. As part of the research work 3D scanner from an open source FabLab project was constructed. In addition, the results for the analysis of the geometry of the point clouds obtained by using a low-cost laser scanner were presented. Also, some analysis of collecting data of different structures (made of various materials such as: glass, wood, paper, gum, plastic, plaster, ceramics, stoneware clay etc. and of different shapes: oval and similar to oval and prism shaped) have been done. The article presents two methods used for analysis: the first one - visual (general comparison between the 3D model and the real object) and the second one - comparative method (comparison between measurements on models and scanned objects using the mean error of a single sample of observations). The analysis showed, that the low-budget ground-based laser scanner FabScan has difficulties with collecting data of non-oval objects. Items built of glass painted black also caused problems for the scanner. In addition, the more details scanned object contains, the lower the accuracy of the collected point-cloud is. Nevertheless, the accuracy of collected data (using oval-straight shaped objects) is satisfactory. The accuracy, in this case, fluctuates between ± 0,4 mm and ± 1,0 mm whereas when using more detailed objects or a rectangular shaped prism the accuracy is much more lower, between 2,9 mm and ± 9,0 mm. Finally, the publication presents the possibility (for the future expansion of

  1. From Heteroaromatic Acids and Imines to Azaspirocycles: Stereoselective Synthesis and 3D Shape Analysis

    PubMed Central

    Chambers, Sarah J.; Coulthard, Graeme; Unsworth, William P.; O'Brien, Peter

    2016-01-01

    Abstract Heteroaromatic carboxylic acids have been directly coupled with imines using propylphosphonic anhydride (T3P) and NEt(iPr)2 to form azaspirocycles via intermediate N‐acyliminium ions. Spirocyclic indolenines (3H‐indoles), azaindolenines, 2H‐pyrroles and 3H‐pyrroles were all accessed using this metal‐free approach. The reactions typically proceed with high diastereoselectivity and 3D shape analysis confirms that the products formed occupy areas of chemical space that are under‐represented in existing drugs and high throughput screening libraries. PMID:26918778

  2. Multivariate statistical analysis as a tool for the segmentation of 3D spectral data.

    PubMed

    Lucas, G; Burdet, P; Cantoni, M; Hébert, C

    2013-01-01

    Acquisition of three-dimensional (3D) spectral data is nowadays common using many different microanalytical techniques. In order to proceed to the 3D reconstruction, data processing is necessary not only to deal with noisy acquisitions but also to segment the data in term of chemical composition. In this article, we demonstrate the value of multivariate statistical analysis (MSA) methods for this purpose, allowing fast and reliable results. Using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) coupled with a focused ion beam (FIB), a stack of spectrum images have been acquired on a sample produced by laser welding of a nickel-titanium wire and a stainless steel wire presenting a complex microstructure. These data have been analyzed using principal component analysis (PCA) and factor rotations. PCA allows to significantly improve the overall quality of the data, but produces abstract components. Here it is shown that rotated components can be used without prior knowledge of the sample to help the interpretation of the data, obtaining quickly qualitative mappings representative of elements or compounds found in the material. Such abundance maps can then be used to plot scatter diagrams and interactively identify the different domains in presence by defining clusters of voxels having similar compositions. Identified voxels are advantageously overlaid on secondary electron (SE) images with higher resolution in order to refine the segmentation. The 3D reconstruction can then be performed using available commercial softwares on the basis of the provided segmentation. To asses the quality of the segmentation, the results have been compared to an EDX quantification performed on the same data. PMID:24035679

  3. Design, synthesis, evaluation and QSAR analysis of N(1)-substituted norcymserine derivatives as selective butyrylcholinesterase inhibitors.

    PubMed

    Takahashi, Jun; Hijikuro, Ichiro; Kihara, Takeshi; Murugesh, Modachur G; Fuse, Shinichiro; Kunimoto, Ryo; Tsumura, Yoshinori; Akaike, Akinori; Niidome, Tetsuhiro; Okuno, Yasushi; Takahashi, Takashi; Sugimoto, Hachiro

    2010-03-01

    We synthesized a series of N(1)-substituted norcymserine derivatives 7a-p and evaluated their anti-cholinesterase activities. In vitro evaluation showed that the pyridinylethyl derivatives 7m-o and the piperidinylethyl derivative 7p improved the anti-butyrylcholinesterase activity by approximately threefold compared to N(1)-phenethylnorcymserine (PEC, 2). A quantitative structure-activity relationship (QSAR) study indicated that logS might be a key feature of the improved compounds.

  4. Development of computer program NAS3D using Vector processing for geometric nonlinear analysis of structures

    NASA Technical Reports Server (NTRS)

    Mangalgiri, P. D.; Prabhakaran, R.

    1986-01-01

    An algorithm for vectorized computation of stiffness matrices of an 8 noded isoparametric hexahedron element for geometric nonlinear analysis was developed. This was used in conjunction with the earlier 2-D program GAMNAS to develop the new program NAS3D for geometric nonlinear analysis. A conventional, modified Newton-Raphson process is used for the nonlinear analysis. New schemes for the computation of stiffness and strain energy release rates is presented. The organization the program is explained and some results on four sample problems are given. The study of CPU times showed that savings by a factor of 11 to 13 were achieved when vectorized computation was used for the stiffness instead of the conventional scalar one. Finally, the scheme of inputting data is explained.

  5. Analysis of Impact of 3D Printing Technology on Traditional Manufacturing Technology

    NASA Astrophysics Data System (ADS)

    Wu, Niyan; Chen, Qi; Liao, Linzhi; Wang, Xin

    With quiet rise of 3D printing technology in automobile, aerospace, industry, medical treatment and other fields, many insiders hold different opinions on its development. This paper objectively analyzes impact of 3D printing technology on mold making technology and puts forward the idea of fusion and complementation of 3D printing technology and mold making technology through comparing advantages and disadvantages of 3D printing mold and traditional mold making technology.

  6. Modification, Biological Evaluation and 3D QSAR Studies of Novel 2-(1,3-Diaryl- 4,5-Dihydro-1H-Pyrazol-5-yl)Phenol Derivatives as Inhibitors of B-Raf Kinase

    PubMed Central

    Tang, Dan-Jie; Yang, Yong-Hua; Zhu, Hai-Liang

    2014-01-01

    A series of novel 2-(1,3-diaryl- 4,5-dihydro-1H-pyrazol-5-yl)phenol derivatives (C1–C24) have been synthesized. The B-Raf inhibitory activity and anti-proliferation activity of these compounds have been tested. Compound C6 displayed the most potent biological activity against B-RafV600E (IC50 = 0.15 µM) and WM266.4 human melanoma cell line (GI50 = 1.75 µM), being comparable with the positive control (Vemurafenib and Erlotinib) and more potent than our previous best compounds. The docking simulation was performed to analyze the probable binding models and poses while the QSAR model was built to check the previous work as well as to introduce new directions. This work aimed at seeking more potent inhibitors as well as discussing some previous findings. As a result, the introduction of ortho-hydroxyl group on 4,5-dihydro-1H-pyrazole skeleton did reinforce the anti-tumor activity while enlarging the group on N-1 of pyrazoline was also helpful. PMID:24827980

  7. 3D finite element model of the diabetic neuropathic foot: a gait analysis driven approach.

    PubMed

    Guiotto, Annamaria; Sawacha, Zimi; Guarneri, Gabriella; Avogaro, Angelo; Cobelli, Claudio

    2014-09-22

    Diabetic foot is an invalidating complication of diabetes that can lead to foot ulcers. Three-dimensional (3D) finite element analysis (FEA) allows characterizing the loads developed in the different anatomical structures of the foot in dynamic conditions. The aim of this study was to develop a subject specific 3D foot FE model (FEM) of a diabetic neuropathic (DNS) and a healthy (HS) subject, whose subject specificity can be found in term of foot geometry and boundary conditions. Kinematics, kinetics and plantar pressure (PP) data were extracted from the gait analysis trials of the two subjects with this purpose. The FEM were developed segmenting bones, cartilage and skin from MRI and drawing a horizontal plate as ground support. Materials properties were adopted from previous literature. FE simulations were run with the kinematics and kinetics data of four different phases of the stance phase of gait (heel strike, loading response, midstance and push off). FEMs were then driven by group gait data of 10 neuropathic and 10 healthy subjects. Model validation focused on agreement between FEM-simulated and experimental PP. The peak values and the total distribution of the pressures were compared for this purpose. Results showed that the models were less robust when driven from group data and underestimated the PP in each foot subarea. In particular in the case of the neuropathic subject's model the mean errors between experimental and simulated data were around the 20% of the peak values. This knowledge is crucial in understanding the aetiology of diabetic foot.

  8. Shape Analysis of 3D Head Scan Data for U.S. Respirator Users

    NASA Astrophysics Data System (ADS)

    Zhuang, Ziqing; Slice, DennisE; Benson, Stacey; Lynch, Stephanie; Viscusi, DennisJ

    2010-12-01

    In 2003, the National Institute for Occupational Safety and Health (NIOSH) conducted a head-and-face anthropometric survey of diverse, civilian respirator users. Of the 3,997 subjects measured using traditional anthropometric techniques, surface scans and 26 three-dimensional (3D) landmark locations were collected for 947 subjects. The objective of this study was to report the size and shape variation of the survey participants using the 3D data. Generalized Procrustes Analysis (GPA) was conducted to standardize configurations of landmarks associated with individuals into a common coordinate system. The superimposed coordinates for each individual were used as commensurate variables that describe individual shape and were analyzed using Principal Component Analysis (PCA) to identify population variation. The first four principal components (PC) account for 49% of the total sample variation. The first PC indicates that overall size is an important component of facial variability. The second PC accounts for long and narrow or short and wide faces. Longer narrow orbits versus shorter wider orbits can be described by PC3, and PC4 represents variation in the degree of ortho/prognathism. Geometric Morphometrics provides a detailed and interpretable assessment of morphological variation that may be useful in assessing respirators and devising new test and certification standards.

  9. Detection of ancient morphology and potential hydrocarbon traps using 3-D seismic data and attribute analysis

    SciTech Connect

    Heggland, R.

    1995-12-31

    This paper presents the use of seismic attributes on 3D data to reveal Tertiary and Cretaceous geological features in Norwegian block 9/2. Some of the features would hardly be possible to map using only 2D seismic data. The method which involves a precise interpretation of horizons, attribute analysis and manipulation of colour displays, may be useful when studying morphology, faults and hydrocarbon traps. The interval of interest in this study was from 0 to 1.5 s TWT. Horizontal displays (timeslices and attribute maps), seemed to highlight very nicely geological features such as shallow channels, fractures, karst topography and faults. The attributes used for mapping these features were amplitude, total reflection energy (a volume or time interval attribute), dip and azimuth. The choice of colour scale and manipulation of colour displays were also critical for the results. The data examples clearly demonstrate how it is possible to achieve a very detailed mapping of geological features using 3D seismic data and attribute analysis. The results of this study were useful for the understanding of hydrocarbon migration paths and hydrocarbon traps.

  10. A coordinate-free method for the analysis of 3D facial change

    NASA Astrophysics Data System (ADS)

    Mao, Zhili; Siebert, Jan Paul; Cockshott, W. Paul; Ayoub, Ashraf Farouk

    2004-05-01

    Euclidean Distance Matrix Analysis (EDMA) is widely held as the most important coordinate-free method by which to analyze landmarks. It has been used extensively in the field of medical anthropometry and has already produced many useful results. Unfortunately this method renders little information regarding the surface on which these points are located and accordingly is inadequate for the 3D analysis of surface anatomy. Here we shall present a new inverse surface flatness metric, the ratio between the Geodesic and the Euclidean inter-landmark distances. Because this metric also only reflects one aspect of three-dimensional shape, i.e. surface flatness, we have combined it with the Euclidean distance to investigate 3D facial change. The goal of this investigation is to be able to analyze three-dimensional facial change in terms of bilateral symmetry as encoded both by surface flatness and by geometric configuration. Our initial study, based on 25 models of surgically managed children (unilateral cleft lip repair) and 40 models of control children at the age of 2 years, indicates that the faces of the surgically managed group were found to be significantly less symmetric than those of the control group in terms of surface flatness, geometric configuration and overall symmetry.

  11. New Approach for 3D Local Structure Refinement Using Non-Muffin-Tin XANES Analysis

    SciTech Connect

    Smolentsev, Grigory; Soldatov, Alexander V.; Feiters, Martin C.

    2007-02-02

    A new technique of 3D local structure refinement using full-potential X-ray absorption near edge structure (XANES) analysis is proposed and demonstrated in application to metalloorganic complexes of Ni. It can be applied to determine local structure in those cases where the muffin-tin approximation used in most full multiple scattering schemes fails. The method is based on the fitting of experimental XANES data using multidimensional interpolation of spectra as a function of structural parameters, recently proposed by us, and ab-initio full potential calculations of XANES using finite difference method. The small number of required ab-initio calculations is the main advantage of the approach, which allows one to use computationally time-expensive non-muffin-tin finite-difference method. The possibility to extract information on bond angles in addition to bond-lengths accessible to standard EXAFS is demonstrated and it opens new perspectives of quantitative XANES analysis as a 3D local structure probe.

  12. A 3D endoscopy reconstruction as a saliency map for analysis of polyp shapes

    NASA Astrophysics Data System (ADS)

    Ruano, Josue; Martínez, Fabio; Gómez, Martín.; Romero, Eduardo

    2015-01-01

    A first diagnosis of colorectal cancer is performed by examination of polyp shape and appearance during an endoscopy routine procedure. However, the video-endoscopy is highly noisy because exacerbated physiological conditions like increased motility or secretion may limit the visual analysis of lesions. In this work a 3D reconstruction of the digestive tract is proposed, facilitating the polyp shape evaluation by highlighting its surface geometry and allowing an analysis from different perspectives. The method starts by a spatio-temporal map, constructed to group the different regions of the tract by their similar dynamic patterns during the sequence. Then, such map was convolved with a second derivative of a Gaussian kernel that emulates the camera distortion and allows to highlight the polyp surface. The position initialization in each frame of the kernel was computed from expert manual delineation and propagated along the sequence based on. Results show reliable reconstructions, with a salient 3D polyp structure that can then be better observed.

  13. QSAR analysis of nitroaromatics' toxicity in Tetrahymena pyriformis: structural factors and possible modes of action

    PubMed Central

    Artemenko, A.G.; Muratov, E. N.; Kuz’min, V.E.; Muratov, N.N.; Varlamova, E.V.; Kuz'mina, A.V.; Gorb, L. G.; Golius, A.; Hill, F.C.; Leszczynski, J.; Tropsha, A.

    2012-01-01

    The Hierarchical Technology for Quantitative Structure - Activity Relationships (HiT QSAR) was applied to 95 diverse nitroaromatic compounds (including some widely known explosives) tested for their toxicity (50% inhibition growth concentration, IGC50) against the ciliate Tetrahymena pyriformis. The dataset was divided into subsets according to putative mechanisms of toxicity. Classification and Regression Trees (CART) approach implemented within HiT QSAR has been used for prediction of mechanism of toxicity for new compounds. The resulting models were shown to have ~80% accuracy for external datasets indicating that the mechanistic dataset division was sensible. Then, Partial Least Squares (PLS) statistical approach was used for the development of 2D QSAR models. Validated PLS models were explored to (i) elucidate the effects of different substituents in nitroaromatic compounds on toxicity; (ii) differentiate compounds by probable mechanisms of toxicity based on their structural descriptors; (iii) analyze the role of various physical-chemical factors responsible for compounds’ toxicity. Models were interpreted in terms of molecular fragments promoting or interfering with toxicity. It was also shown that mutual influence of substituents in benzene ring plays the determining role in toxicity variation. Although chemical mechanism based models were statistically significant and externally predictive (R2ext=0.64 for the external set of 63 nitroaromatics identified after all calculations have been completed), they were also shown to have limited coverage (57% for modeling and 76% for external set). PMID:21714735

  14. In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer's disease

    PubMed Central

    Islam, Md. Rezaul; Zaman, Aubhishek; Jahan, Iffat; Chakravorty, Rajib; Chakraborty, Sajib

    2013-01-01

    Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects. Aims The aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate. Methods and materials Physico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis. Result and discussion Quercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was −8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score −7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity. Conclusion This in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this

  15. An Analysis on 3d Marine Csem Responses Based on a Finite Difference Method

    NASA Astrophysics Data System (ADS)

    Han, N.; Nam, M.; Kim, H.

    2010-12-01

    Three-dimensional (3D) marine controlled-source electromagnetic (CSEM) data are analyzed using a modeling algorithm based on a finite difference method. The algorithm employs the secondary-field formulation of a vector Helmholtz equation for electric fields to avoid singularity problems. Primary fields are calculated analytically using a numerical filter for the Hankel transform for a three-layered 1D background model, that consists of air, sea and sub-seafloor; the model includes the air layer to consider air waves. Several numerical filters for the Hankel transform are compared in terms of their accuracy and computation time. Using the analytically-calculated primary fields, we compute secondary fields using a finite difference method with a staggered grid. The grid defines electric fields along cell edges while magnetic fields at cell faces. We verified the developed modeling algorithm using not only 1D analytic solutions but also responses for a 3D model, that are computed by other algorithms. Using disk models, this study analyzes marine CSEM data for horizontal and vertical electric and magnetic dipole sources to determine the most effective source-receiver configuration for the exploration of 3D thin and resistive hydrocarbon targets. Numerical results show that marine CSEM has exciting potential for oilfield characterization. Further, air waves should be properly considered in modeling and interpretation of marine CSEM data because they have great effects on marine CSEM data. For an analysis on bathymetry effects, a stepwise-bathymetry model was constructed. Bathymetry causes significant effects on marine CSEM data because transmitter and receivers are located very far each other. We propose a bathymetry correction method for a proper interpretation of marine CSEM data distorted by bathymetry.

  16. Robust object tracking techniques for vision-based 3D motion analysis applications

    NASA Astrophysics Data System (ADS)

    Knyaz, Vladimir A.; Zheltov, Sergey Y.; Vishnyakov, Boris V.

    2016-04-01

    Automated and accurate spatial motion capturing of an object is necessary for a wide variety of applications including industry and science, virtual reality and movie, medicine and sports. For the most part of applications a reliability and an accuracy of the data obtained as well as convenience for a user are the main characteristics defining the quality of the motion capture system. Among the existing systems for 3D data acquisition, based on different physical principles (accelerometry, magnetometry, time-of-flight, vision-based), optical motion capture systems have a set of advantages such as high speed of acquisition, potential for high accuracy and automation based on advanced image processing algorithms. For vision-based motion capture accurate and robust object features detecting and tracking through the video sequence are the key elements along with a level of automation of capturing process. So for providing high accuracy of obtained spatial data the developed vision-based motion capture system "Mosca" is based on photogrammetric principles of 3D measurements and supports high speed image acquisition in synchronized mode. It includes from 2 to 4 technical vision cameras for capturing video sequences of object motion. The original camera calibration and external orientation procedures provide the basis for high accuracy of 3D measurements. A set of algorithms as for detecting, identifying and tracking of similar targets, so for marker-less object motion capture is developed and tested. The results of algorithms' evaluation show high robustness and high reliability for various motion analysis tasks in technical and biomechanics applications.

  17. Structural development of benzhydrol-type 1'-acetoxychavicol acetate (ACA) analogs as human leukemia cell-growth inhibitors based on quantitative structure-activity relationship (QSAR) analysis.

    PubMed

    Misawa, Takashi; Aoyama, Hiroshi; Furuyama, Taniyuki; Dodo, Kosuke; Sagawa, Morihiko; Miyachi, Hiroyuki; Kizaki, Masahiro; Hashimoto, Yuichi

    2008-10-01

    Benzhydrol-type analogs of 1'-acetoxychavicol acetate (ACA) were developed as inhibitors of human leukemia HL-60 cell growth based on quantitative structure-activity relationship (QSAR) analysis. An analog containing an anthracenyl moiety (8) was a potent inhibitor with the IC(50) value of 0.12 microM.

  18. 3D geometry analysis of the medial meniscus--a statistical shape modeling approach.

    PubMed

    Vrancken, A C T; Crijns, S P M; Ploegmakers, M J M; O'Kane, C; van Tienen, T G; Janssen, D; Buma, P; Verdonschot, N

    2014-10-01

    The geometry-dependent functioning of the meniscus indicates that detailed knowledge on 3D meniscus geometry and its inter-subject variation is essential to design well functioning anatomically shaped meniscus replacements. Therefore, the aim of this study was to quantify 3D meniscus geometry and to determine whether variation in medial meniscus geometry is size- or shape-driven. Also we performed a cluster analysis to identify distinct morphological groups of medial menisci and assessed whether meniscal geometry is gender-dependent. A statistical shape model was created, containing the meniscus geometries of 35 subjects (20 females, 15 males) that were obtained from MR images. A principal component analysis was performed to determine the most important modes of geometry variation and the characteristic changes per principal component were evaluated. Each meniscus from the original dataset was then reconstructed as a linear combination of principal components. This allowed the comparison of male and female menisci, and a cluster analysis to determine distinct morphological meniscus groups. Of the variation in medial meniscus geometry, 53.8% was found to be due to primarily size-related differences and 29.6% due to shape differences. Shape changes were most prominent in the cross-sectional plane, rather than in the transverse plane. Significant differences between male and female menisci were only found for principal component 1, which predominantly reflected size differences. The cluster analysis resulted in four clusters, yet these clusters represented two statistically different meniscal shapes, as differences between cluster 1, 2 and 4 were only present for principal component 1. This study illustrates that differences in meniscal geometry cannot be explained by scaling only, but that different meniscal shapes can be distinguished. Functional analysis, e.g. through finite element modeling, is required to assess whether these distinct shapes actually influence

  19. Analysis of bite marks in foodstuffs by computer tomography (cone beam CT)--3D reconstruction.

    PubMed

    Marques, Jeidson; Musse, Jamilly; Caetano, Catarina; Corte-Real, Francisco; Corte-Real, Ana Teresa

    2013-12-01

    The use of three-dimensional (3D) analysis of forensic evidence is highlighted in comparison with traditional methods. This three-dimensional analysis is based on the registration of the surface from a bitten object. The authors propose to use Cone Beam Computed Tomography (CBCT), which is used in dental practice, in order to study the surface and interior of bitten objects and dental casts of suspects. In this study, CBCT is applied to the analysis of bite marks in foodstuffs, which may be found in a forensic case scenario. 6 different types of foodstuffs were used: chocolate, cheese, apple, chewing gum, pizza and tart (flaky pastry and custard). The food was bitten into and dental casts of the possible suspects were made. The dental casts and bitten objects were registered using an x-ray source and the CBCT equipment iCAT® (Pennsylvania, EUA). The software InVivo5® (Anatomage Inc, EUA) was used to visualize and analyze the tomographic slices and 3D reconstructions of the objects. For each material an estimate of its density was assessed by two methods: HU values and specific gravity. All the used materials were successfully reconstructed as good quality 3D images. The relative densities of the materials in study were compared. Amongst the foodstuffs, the chocolate had the highest density (median value 100.5 HU and 1,36 g/cm(3)), while the pizza showed to have the lowest (median value -775 HU and 0,39 g/cm(3)), on both scales. Through tomographic slices and three-dimensional reconstructions it was possible to perform the metric analysis of the bite marks in all the foodstuffs, except for the pizza. These measurements could also be obtained from the dental casts. The depth of the bite mark was also successfully determined in all the foodstuffs except for the pizza. Cone Beam Computed Tomography has the potential to become an important tool for forensic sciences, namely for the registration and analysis of bite marks in foodstuffs that may be found in a crime

  20. Analysis of bite marks in foodstuffs by computer tomography (cone beam CT)--3D reconstruction.

    PubMed

    Marques, Jeidson; Musse, Jamilly; Caetano, Catarina; Corte-Real, Francisco; Corte-Real, Ana Teresa

    2013-12-01

    The use of three-dimensional (3D) analysis of forensic evidence is highlighted in comparison with traditional methods. This three-dimensional analysis is based on the registration of the surface from a bitten object. The authors propose to use Cone Beam Computed Tomography (CBCT), which is used in dental practice, in order to study the surface and interior of bitten objects and dental casts of suspects. In this study, CBCT is applied to the analysis of bite marks in foodstuffs, which may be found in a forensic case scenario. 6 different types of foodstuffs were used: chocolate, cheese, apple, chewing gum, pizza and tart (flaky pastry and custard). The food was bitten into and dental casts of the possible suspects were made. The dental casts and bitten objects were registered using an x-ray source and the CBCT equipment iCAT® (Pennsylvania, EUA). The software InVivo5® (Anatomage Inc, EUA) was used to visualize and analyze the tomographic slices and 3D reconstructions of the objects. For each material an estimate of its density was assessed by two methods: HU values and specific gravity. All the used materials were successfully reconstructed as good quality 3D images. The relative densities of the materials in study were compared. Amongst the foodstuffs, the chocolate had the highest density (median value 100.5 HU and 1,36 g/cm(3)), while the pizza showed to have the lowest (median value -775 HU and 0,39 g/cm(3)), on both scales. Through tomographic slices and three-dimensional reconstructions it was possible to perform the metric analysis of the bite marks in all the foodstuffs, except for the pizza. These measurements could also be obtained from the dental casts. The depth of the bite mark was also successfully determined in all the foodstuffs except for the pizza. Cone Beam Computed Tomography has the potential to become an important tool for forensic sciences, namely for the registration and analysis of bite marks in foodstuffs that may be found in a crime

  1. Advanced methods for 3-D inelastic structural analysis for hot engine structures

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.

    1989-01-01

    Three-dimensional Inelastic Analysis Methods are described. These methods were incorporated into a series of new computer codes embodying a progression of mathematical models (mechanics of materials, specialty finite element, boundary element) for streamlined analysis of hot engine structures such as: (1) combustor liners, (2) turbine blades, and (3) turbine vanes. These models address the effects of high temperatures and thermal/mechanical loadings on the local (stress/strain) and global (displacements, frequencies, amplitudes, buckling) structural behavior of the three respective components. The methods and the three computer codes, referred to as MOMM (Mechanics Of Materials Model), MHOST (MARC-Hot Section Technology), and BEST3D (Boundary Element Stress Technology), have been developed and are briefly described.

  2. The Use of Atomic Force Microscopy for 3D Analysis of Nucleic Acid Hybridization on Microarrays

    PubMed Central

    Dubrovin, E. V.; Presnova, G. V.; Rubtsova, M. Yu.; Egorov, A. M.; Grigorenko, V. G.; Yaminsky, I. V.

    2015-01-01

    Oligonucleotide microarrays are considered today to be one of the most efficient methods of gene diagnostics. The capability of atomic force microscopy (AFM) to characterize the three-dimensional morphology of single molecules on a surface allows one to use it as an effective tool for the 3D analysis of a microarray for the detection of nucleic acids. The high resolution of AFM offers ways to decrease the detection threshold of target DNA and increase the signal-to-noise ratio. In this work, we suggest an approach to the evaluation of the results of hybridization of gold nanoparticle-labeled nucleic acids on silicon microarrays based on an AFM analysis of the surface both in air and in liquid which takes into account of their three-dimensional structure. We suggest a quantitative measure of the hybridization results which is based on the fraction of the surface area occupied by the nanoparticles. PMID:26085952

  3. On 3-D inelastic analysis methods for hot section components. Volume 1: Special finite element models

    NASA Technical Reports Server (NTRS)

    Nakazawa, S.

    1987-01-01

    This Annual Status Report presents the results of work performed during the third year of the 3-D Inelastic Analysis Methods for Hot Section Components program (NASA Contract NAS3-23697). The objective of the program is to produce a series of new computer codes that permit more accurate and efficient three-dimensional analysis of selected hot section components, i.e., combustor liners, turbine blades, and turbine vanes. The computer codes embody a progression of mathematical models and are streamlined to take advantage of geometrical features, loading conditions, and forms of material response that distinguish each group of selected components. This report is presented in two volumes. Volume 1 describes effort performed under Task 4B, Special Finite Element Special Function Models, while Volume 2 concentrates on Task 4C, Advanced Special Functions Models.

  4. Fit-sphere unwrapping and performance analysis of 3D fingerprints.

    PubMed

    Wang, Yongchang; Lau, Daniel L; Hassebrook, Laurence G

    2010-02-01

    To solve problems associated with conventional 2D fingerprint acquisition processes including skin deformations and print smearing, we developed a noncontact 3D fingerprint scanner employing structured light illumination that, in order to be backwards compatible with existing 2D fingerprint recognition systems, requires a method of unwrapping the 3D scans into 2D equivalent prints. For the latter purpose of virtually flattening a 3D print, this paper introduces a fit-sphere unwrapping algorithm. Taking advantage of detailed 3D information, the proposed method defuses the unwrapping distortion by controlling the distances between neighboring points. Experimental results will demonstrate the high quality and recognition performance of the 3D unwrapped prints versus traditionally collected 2D prints. Furthermore, by classifying the 3D database into high- and low-quality data sets, we demonstrate that the relationship between quality and recognition performance holding for conventional 2D prints is achieved for 3D unwrapped fingerprints.

  5. Automated extraction and analysis of rock discontinuity characteristics from 3D point clouds

    NASA Astrophysics Data System (ADS)

    Bianchetti, Matteo; Villa, Alberto; Agliardi, Federico; Crosta, Giovanni B.

    2016-04-01

    A reliable characterization of fractured rock masses requires an exhaustive geometrical description of discontinuities, including orientation, spacing, and size. These are required to describe discontinuum rock mass structure, perform Discrete Fracture Network and DEM modelling, or provide input for rock mass classification or equivalent continuum estimate of rock mass properties. Although several advanced methodologies have been developed in the last decades, a complete characterization of discontinuity geometry in practice is still challenging, due to scale-dependent variability of fracture patterns and difficult accessibility to large outcrops. Recent advances in remote survey techniques, such as terrestrial laser scanning and digital photogrammetry, allow a fast and accurate acquisition of dense 3D point clouds, which promoted the development of several semi-automatic approaches to extract discontinuity features. Nevertheless, these often need user supervision on algorithm parameters which can be difficult to assess. To overcome this problem, we developed an original Matlab tool, allowing fast, fully automatic extraction and analysis of discontinuity features with no requirements on point cloud accuracy, density and homogeneity. The tool consists of a set of algorithms which: (i) process raw 3D point clouds, (ii) automatically characterize discontinuity sets, (iii) identify individual discontinuity surfaces, and (iv) analyse their spacing and persistence. The tool operates in either a supervised or unsupervised mode, starting from an automatic preliminary exploration data analysis. The identification and geometrical characterization of discontinuity features is divided in steps. First, coplanar surfaces are identified in the whole point cloud using K-Nearest Neighbor and Principal Component Analysis algorithms optimized on point cloud accuracy and specified typical facet size. Then, discontinuity set orientation is calculated using Kernel Density Estimation and

  6. Analysis of passive cardiac constitutive laws for parameter estimation using 3D tagged MRI.

    PubMed

    Hadjicharalambous, Myrianthi; Chabiniok, Radomir; Asner, Liya; Sammut, Eva; Wong, James; Carr-White, Gerald; Lee, Jack; Razavi, Reza; Smith, Nicolas; Nordsletten, David

    2015-08-01

    An unresolved issue in patient-specific models of cardiac mechanics is the choice of an appropriate constitutive law, able to accurately capture the passive behavior of the myocardium, while still having uniquely identifiable parameters tunable from available clinical data. In this paper, we aim to facilitate this choice by examining the practical identifiability and model fidelity of constitutive laws often used in cardiac mechanics. Our analysis focuses on the use of novel 3D tagged MRI, providing detailed displacement information in three dimensions. The practical identifiability of each law is examined by generating synthetic 3D tags from in silico simulations, allowing mapping of the objective function landscape over parameter space and comparison of minimizing parameter values with original ground truth values. Model fidelity was tested by comparing these laws with the more complex transversely isotropic Guccione law, by characterizing their passive end-diastolic pressure-volume relation behavior, as well as by considering the in vivo case of a healthy volunteer. These results show that a reduced form of the Holzapfel-Ogden law provides the best balance between identifiability and model fidelity across the tests considered. PMID:25510227

  7. Comparative 3D genome structure analysis of the fission and the budding yeast.

    PubMed

    Gong, Ke; Tjong, Harianto; Zhou, Xianghong Jasmine; Alber, Frank

    2015-01-01

    We studied the 3D structural organization of the fission yeast genome, which emerges from the tethering of heterochromatic regions in otherwise randomly configured chromosomes represented as flexible polymer chains in an nuclear environment. This model is sufficient to explain in a statistical manner many experimentally determined distinctive features of the fission yeast genome, including chromatin interaction patterns from Hi-C experiments and the co-locations of functionally related and co-expressed genes, such as genes expressed by Pol-III. Our findings demonstrate that some previously described structure-function correlations can be explained as a consequence of random chromatin collisions driven by a few geometric constraints (mainly due to centromere-SPB and telomere-NE tethering) combined with the specific gene locations in the chromosome sequence. We also performed a comparative analysis between the fission and budding yeast genome structures, for which we previously detected a similar organizing principle. However, due to the different chromosome sizes and numbers, substantial differences are observed in the 3D structural genome organization between the two species, most notably in the nuclear locations of orthologous genes, and the extent of nuclear territories for genes and chromosomes. However, despite those differences, remarkably, functional similarities are maintained, which is evident when comparing spatial clustering of functionally related genes in both yeasts. Functionally related genes show a similar spatial clustering behavior in both yeasts, even though their nuclear locations are largely different between the yeast species.

  8. SAFE-3D analysis of a piezoelectric transducer to excite guided waves in a rail web

    NASA Astrophysics Data System (ADS)

    Ramatlo, Dineo A.; Long, Craig S.; Loveday, Philip W.; Wilke, Daniel N.

    2016-02-01

    Our existing Ultrasonic Broken Rail Detection system detects complete breaks and primarily uses a propagating mode with energy concentrated in the head of the rail. Previous experimental studies have demonstrated that a mode with energy concentrated in the head of the rail, is capable of detecting weld reflections at long distances. Exploiting a mode with energy concentrated in the web of the rail would allow us to effectively detect defects in the web of the rail and could also help to distinguish between reflections from welds and cracks. In this paper, we will demonstrate the analysis of a piezoelectric transducer attached to the rail web. The forced response at different frequencies is computed by the Semi-Analytical Finite Element (SAFE) method and compared to a full three-dimensional finite element method using ABAQUS. The SAFE method only requires the rail track cross-section to be meshed using two-dimensional elements. The ABAQUS model in turn requires a full three-dimensional discretisation of the rail track. The SAFE approach can yield poor predictions at cut-on frequencies associated with other modes in the rail. Problematic frequencies are identified and a suitable frequency range identified for transducer design. The forced response results of the two methods were found to be in good agreement with each other. We then use a previously developed SAFE-3D method to analyse a practical transducer over the selected frequency range. The results obtained from the SAFE-3D method are in good agreement with experimental measurements.

  9. Automated diagnosis of fetal alcohol syndrome using 3D facial image analysis

    PubMed Central

    Fang, Shiaofen; McLaughlin, Jason; Fang, Jiandong; Huang, Jeffrey; Autti-Rämö, Ilona; Fagerlund, Åse; Jacobson, Sandra W.; Robinson, Luther K.; Hoyme, H. Eugene; Mattson, Sarah N.; Riley, Edward; Zhou, Feng; Ward, Richard; Moore, Elizabeth S.; Foroud, Tatiana

    2012-01-01

    Objectives Use three-dimensional (3D) facial laser scanned images from children with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis technique that can reliably and accurately identify individuals prenatally exposed to alcohol. Methods A detailed dysmorphology evaluation, history of prenatal alcohol exposure, and 3D facial laser scans were obtained from 149 individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern recognition techniques were used to automatically identify a set of facial features that best discriminated individuals with FAS from controls in each sample. Results An automated feature detection and analysis technique was developed and applied to the two study populations. A unique set of facial regions and features were identified for each population that accurately discriminated FAS and control faces without any human intervention. Conclusion Our results demonstrate that computer algorithms can be used to automatically detect facial features that can discriminate FAS and control faces. PMID:18713153

  10. QSAR Methods.

    PubMed

    Gini, Giuseppina

    2016-01-01

    In this chapter, we introduce the basis of computational chemistry and discuss how computational methods have been extended to some biological properties and toxicology, in particular. Since about 20 years, chemical experimentation is more and more replaced by modeling and virtual experimentation, using a large core of mathematics, chemistry, physics, and algorithms. Then we see how animal experiments, aimed at providing a standardized result about a biological property, can be mimicked by new in silico methods. Our emphasis here is on toxicology and on predicting properties through chemical structures. Two main streams of such models are available: models that consider the whole molecular structure to predict a value, namely QSAR (Quantitative Structure Activity Relationships), and models that find relevant substructures to predict a class, namely SAR. The term in silico discovery is applied to chemical design, to computational toxicology, and to drug discovery. We discuss how the experimental practice in biological science is moving more and more toward modeling and simulation. Such virtual experiments confirm hypotheses, provide data for regulation, and help in designing new chemicals. PMID:27311459

  11. 3D GeoWall Analysis System for Shuttle External Tank Foreign Object Debris Events

    NASA Technical Reports Server (NTRS)

    Brown, Richard; Navard, Andrew; Spruce, Joseph

    2010-01-01

    An analytical, advanced imaging method has been developed for the initial monitoring and identification of foam debris and similar anomalies that occur post-launch in reference to the space shuttle s external tank (ET). Remote sensing technologies have been used to perform image enhancement and analysis on high-resolution, true-color images collected with the DCS 760 Kodak digital camera located in the right umbilical well of the space shuttle. Improvements to the camera, using filters, have added sharpness/definition to the image sets; however, image review/analysis of the ET has been limited by the fact that the images acquired by umbilical cameras during launch are two-dimensional, and are usually nonreferenceable between frames due to rotation translation of the ET as it falls away from the space shuttle. Use of stereo pairs of these images can enable strong visual indicators that can immediately portray depth perception of damaged areas or movement of fragments between frames is not perceivable in two-dimensional images. A stereoscopic image visualization system has been developed to allow 3D depth perception of stereo-aligned image pairs taken from in-flight umbilical and handheld digital shuttle cameras. This new system has been developed to augment and optimize existing 2D monitoring capabilities. Using this system, candidate sequential image pairs are identified for transformation into stereo viewing pairs. Image orientation is corrected using control points (similar points) between frames to place the two images in proper X-Y viewing perspective. The images are then imported into the WallView stereo viewing software package. The collected control points are used to generate a transformation equation that is used to re-project one image and effectively co-register it to the other image. The co-registered, oriented image pairs are imported into a WallView image set and are used as a 3D stereo analysis slide show. Multiple sequential image pairs can be used

  12. Wavelet-based fMRI analysis: 3-D denoising, signal separation, and validation metrics

    PubMed Central

    Khullar, Siddharth; Michael, Andrew; Correa, Nicolle; Adali, Tulay; Baum, Stefi A.; Calhoun, Vince D.

    2010-01-01

    We present a novel integrated wavelet-domain based framework (w-ICA) for 3-D de-noising functional magnetic resonance imaging (fMRI) data followed by source separation analysis using independent component analysis (ICA) in the wavelet domain. We propose the idea of a 3-D wavelet-based multi-directional de-noising scheme where each volume in a 4-D fMRI data set is sub-sampled using the axial, sagittal and coronal geometries to obtain three different slice-by-slice representations of the same data. The filtered intensity value of an arbitrary voxel is computed as an expected value of the de-noised wavelet coefficients corresponding to the three viewing geometries for each sub-band. This results in a robust set of de-noised wavelet coefficients for each voxel. Given the decorrelated nature of these de-noised wavelet coefficients; it is possible to obtain more accurate source estimates using ICA in the wavelet domain. The contributions of this work can be realized as two modules. First, the analysis module where we combine a new 3-D wavelet denoising approach with better signal separation properties of ICA in the wavelet domain, to yield an activation component that corresponds closely to the true underlying signal and is maximally independent with respect to other components. Second, we propose and describe two novel shape metrics for post-ICA comparisons between activation regions obtained through different frameworks. We verified our method using simulated as well as real fMRI data and compared our results against the conventional scheme (Gaussian smoothing + spatial ICA: s-ICA). The results show significant improvements based on two important features: (1) preservation of shape of the activation region (shape metrics) and (2) receiver operating characteristic (ROC) curves. It was observed that the proposed framework was able to preserve the actual activation shape in a consistent manner even for very high noise levels in addition to significant reduction in false

  13. 3D pore-network analysis and permeability estimation of deformation bands hosted in carbonate grainstones.

    NASA Astrophysics Data System (ADS)

    Zambrano, Miller; Tondi, Emanuele; Mancini, Lucia; Trias, F. Xavier; Arzilli, Fabio; Lanzafame, Gabriele; Aibibula, Nijiati

    2016-04-01

    In porous rocks strain is commonly localized in narrow Deformation Bands (DBs), where the petrophysical properties are significantly modified with respect the pristine rock. As a consequence, DBs could have an important effect on production and development of porous reservoirs representing baffles zones or, in some cases, contribute to reservoir compartmentalization. Taking in consideration that the decrease of permeability within DBs is related to changes in the porous network properties (porosity, connectivity) and the pores morphology (size distribution, specific surface area), an accurate porous network characterization is useful for understanding both the effect of deformation banding on the porous network and their influence upon fluid flow through the deformed rocks. In this work, a 3D characterization of the microstructure and texture of DBs hosted in porous carbonate grainstones was obtained at the Elettra laboratory (Trieste, Italy) by using two different techniques: phase-contrast synchrotron radiation computed microtomography (micro-CT) and microfocus X-ray micro-CT. These techniques are suitable for addressing quantitative analysis of the porous network and implementing Computer Fluid Dynamics (CFD)experiments in porous rocks. Evaluated samples correspond to grainstones highly affected by DBs exposed in San Vito Lo Capo peninsula (Sicily, Italy), Favignana Island (Sicily, Italy) and Majella Mountain (Abruzzo, Italy). For the analysis, the data were segmented in two main components porous and solid phases. The properties of interest are porosity, connectivity, a grain and/or porous textural properties, in order to differentiate host rock and DBs in different zones. Permeability of DB and surrounding host rock were estimated by the implementation of CFD experiments, permeability results are validated by comparing with in situ measurements. In agreement with previous studies, the 3D image analysis and flow simulation indicate that DBs could be constitute

  14. Theoretical studies on QSAR and mechanism of 2-indolinone derivatives as tubulin inhibitors

    NASA Astrophysics Data System (ADS)

    Liao, Si Yan; Qian, Li; Miao, Ti Fang; Lu, Hai Liang; Zheng, Kang Cheng

    The theoretical studies on three-dimensional quantitative structure activity relationship (3D-QSAR) and action mechanism of a series of 2-indolinone derivatives as tubulin inhibitors against human breast cancer cell line MDA-MB-231 have been carried out. The established 3D-QSAR model from the comparative molecular field analysis (CoMFA) shows not only significant statistical quality but also predictive ability, with high correlation coefficient (R2 = 0.986) and cross-validation coefficient (q2 = 0.683). In particular, the appropriate binding orientations and conformations of these 2-indolinone derivatives interacting with tubulin are located by docking study, and it is very interesting to find that the plot of the energy scores of these compounds in DOCK versus the corresponding experimental pIC50 values exhibits a considerable linear correlation. Therefore, the inhibition mechanism that 2-indolinone derivatives were regarded as tubulin inhibitors can be theoretically confirmed. Based on such an inhibition mechanism along with 3D-QSAR results, some important factors improving the activities of these compounds were discussed in detail. These factors can be summarized as follows: the H atom adopted as substituent R1, the substituent R2 with higher electropositivity and smaller bulk, the substituents R4-R6 (on the phenyl ring) with higher electropositivity and larger bulk, and so on. These results can offer useful theoretical references for understanding the action mechanism, designing more potent inhibitors, and predicting their activities prior to synthesis.

  15. Inlining 3d Reconstruction, Multi-Source Texture Mapping and Semantic Analysis Using Oblique Aerial Imagery

    NASA Astrophysics Data System (ADS)

    Frommholz, D.; Linkiewicz, M.; Poznanska, A. M.

    2016-06-01

    This paper proposes an in-line method for the simplified reconstruction of city buildings from nadir and oblique aerial images that at the same time are being used for multi-source texture mapping with minimal resampling. Further, the resulting unrectified texture atlases are analyzed for façade elements like windows to be reintegrated into the original 3D models. Tests on real-world data of Heligoland/ Germany comprising more than 800 buildings exposed a median positional deviation of 0.31 m at the façades compared to the cadastral map, a correctness of 67% for the detected windows and good visual quality when being rendered with GPU-based perspective correction. As part of the process building reconstruction takes the oriented input images and transforms them into dense point clouds by semi-global matching (SGM). The point sets undergo local RANSAC-based regression and topology analysis to detect adjacent planar surfaces and determine their semantics. Based on this information the roof, wall and ground surfaces found get intersected and limited in their extension to form a closed 3D building hull. For texture mapping the hull polygons are projected into each possible input bitmap to find suitable color sources regarding the coverage and resolution. Occlusions are detected by ray-casting a full-scale digital surface model (DSM) of the scene and stored in pixel-precise visibility maps. These maps are used to derive overlap statistics and radiometric adjustment coefficients to be applied when the visible image parts for each building polygon are being copied into a compact texture atlas without resampling whenever possible. The atlas bitmap is passed to a commercial object-based image analysis (OBIA) tool running a custom rule set to identify windows on the contained façade patches. Following multi-resolution segmentation and classification based on brightness and contrast differences potential window objects are evaluated against geometric constraints and

  16. Motion error analysis of the 3D coordinates of airborne lidar for typical terrains

    NASA Astrophysics Data System (ADS)

    Peng, Tao; Lan, Tian; Ni, Guoqiang

    2013-07-01

    A motion error model of 3D coordinates is established and the impact on coordinate errors caused by the non-ideal movement of the airborne platform is analyzed. The simulation results of the model show that when the lidar system operates at high altitude, the influence on the positioning errors derived from laser point cloud spacing is small. For the model the positioning errors obey simple harmonic vibration whose amplitude envelope gradually reduces with the increase of the vibration frequency. When the vibration period number is larger than 50, the coordinate errors are almost uncorrelated with time. The elevation error is less than the plane error and in the plane the error in the scanning direction is less than the error in the flight direction. Through the analysis of flight test data, the conclusion is verified.

  17. 3D thermal analysis of rectangular microscale inorganic light-emitting diodes in a pulsed operation

    NASA Astrophysics Data System (ADS)

    Cui, Y.; Bian, Z.; Li, Y.; Xing, Y.; Song, J.

    2016-10-01

    Microscale inorganic light-emitting diodes (µ-ILEDs) have attracted much attention due to their excellent performance in biointegrated applications such as optogenetics. The thermal behaviors of µ-ILEDs are critically important since a certain temperature increase may degrade the LED performance and cause tissue lesion. The µ-ILEDs in a pulsed operation offer an advantage in thermal management. In this paper, a 3D analytic model, as validated by finite element analysis, is developed to study the thermal response of rectangular µ-ILEDs in a pulsed operation. A scaling law for the maximum normalized temperature increase of rectangular µ-ILEDs in terms of non-dimensional parameters is established. The influences of geometric (i.e. shape factor) and loading parameters (e.g. duty cycle and period) on the temperature increase are systematically investigated. These results are very helpful in designing µ-ILEDs by providing guidelines to avoid adverse thermal effects.

  18. Analysis of Composite Panel-Stiffener Debonding Using a Shell/3D Modeling Technique

    NASA Technical Reports Server (NTRS)

    Krueger, Ronald; Minguet, Pierre J.

    2006-01-01

    Interlaminar fracture mechanics has proven useful for characterizing the onset of delaminations in composites and has been used with limited success primarily to investigate onset in fracture toughness specimens and laboratory size coupon type specimens. Future acceptance of the methodology by industry and certification authorities however, requires the successful demonstration of the methodology on structural level. For this purpose a panel was selected that was reinforced with stringers. Shear loading cases the panel to buckle and the resulting out-of-plane deformations initiate skin/stringer separation at the location of an embedded defect. For finite element analysis, the panel and surrounding load fixture were modeled with shell element. A small section of the stringer foot and the panel in the vicinity of the embedded defect were modeled with a local 3D solid model. A failure index was calculated by correlating computed mixed-mode failure criterion of the graphite/epoxy material.

  19. A 3-D Magnetic Analysis of a Linear Alternator For a Stirling Power System

    NASA Technical Reports Server (NTRS)

    Geng, Steven M.; Schwarze, Gene E.; Niedra, Janis M.

    2000-01-01

    The NASA Glenn Research Center and the Department of Energy (DOE) are developing advanced radioisotope Stirling convertors, under contract with Stirling Technology Company (STC), for space applications. Of critical importance to the successful development of the Stirling convertor for space power applications is the development of a lightweight and highly efficient linear alternator. This paper presents a 3-D finite element method (FEM) approach for evaluating Stirling convertor linear alternators. Preliminary correlations with open-circuit voltage measurements provide an encouraging level of confidence in the model. Spatial plots of magnetic field strength (H) are presented in the region of the exciting permanent magnets. These plots identify regions of high H, where at elevated temperature and under electrical load, the potential to alter the magnetic moment of the magnets exists. This implies the need for further testing and analysis.

  20. 3D finite element analysis on esthetic indirect dental restorations under thermal and mechanical loading.

    PubMed

    Cornacchia, Tulimar P M; Las Casas, Estevam B; Cimini, Carlos Alberto; Peixoto, Rodrigo G

    2010-11-01

    Thermo-mechanical finite element analyses in 3-D models are described for determination of the stress levels due to thermal and mechanical loads in a healthy and restored tooth. Transient thermo-mechanical analysis simulating the ingestion of cold and hot drinks was performed to determine the temperature distribution in the models of the teeth, followed by linear elastic stress analyses. The thermal loads were applied on the occlusal and lingual surfaces. Subsequently, coupled variation of the temperature and mastication loading was considered. The vertical loading was distributed at occlusal points, adding up to 180 N. Maximum stresses were verified in resin restoration under thermal loads. When studying coupled effect of mechanical loading with that arising from thermal effects, higher tensile stress values occurred in porcelain restorations, especially at the restoration-dentin interface. Regions of high tensile stress were detected and their possible clinical significance with respect to restoration damage and microleakage were discussed.

  1. The 3D EdgeRunner Pipeline: a novel shape-based analysis for neoplasms characterization

    NASA Astrophysics Data System (ADS)

    Yepes-C, Fernando; Johnson, Rebecca; Lao, Yi; Hwang, Darryl; Coloigner, Julie; Yap, Felix; Bushan, Desai; Cheng, Phillip; Gill, Inderbir; Duddalwar, Vinay; Lepore, Natasha

    2016-03-01

    The characterization of tumors after being imaged is currently a qualitative process performed by skilled professionals. If we can aid their diagnosis by identifying quantifiable features associated with tumor classification, we may avoid invasive procedures such as biopsies and enhance efficiency. The aim of this paper is to describe the 3D EdgeRunner Pipeline which characterizes the shape of a tumor. Shape analysis is relevant as malignant tumors tend to be more lobular and benign ones tare generally more symmetrical. The method described considers the distance from each point on the edge of the tumor to the centre of a synthetically created field of view. The method then determines coordinates where the measured distances are rapidly changing (peaks) using a second derivative found by five point differentiation. The list of coordinates considered to be peaks can then be used as statistical data to compare tumors quantitatively. We have found this process effectively captures the peaks on a selection of kidney tumors.

  2. 3D Plasma Clusters: Analysis of dynamical evolution and individual particle interaction

    SciTech Connect

    Antonova, T.; Thomas, H. M.; Morfill, G. E.; Annaratone, B. M.

    2008-09-07

    3D plasma clusters (up to 100 particles) have been built inside small (32 mm{sup 3}) plasma volume in gravity. It has been estimated that the external confinement has a negligible influence on the processes inside the clusters. At such conditions the analysis of dynamical evolution and individual particle interactions have shown that the binary interaction among particles in addition to the repelling Coulomb force exhibits also an attractive part. The tendency of the systems to approach the state with minimum energy by rearranging particles inside has been detected. The measured 63 particles' cluster vibrations are in close agreement with vibrations of a drop with surface tension. This indicates that even a 63 particle cluster already exhibits properties normally associated with the cooperative regime.

  3. 3D Plasma Clusters: Analysis of dynamical evolution and individual particle interaction

    NASA Astrophysics Data System (ADS)

    Antonova, T.; Annaratone, B. M.; Thomas, H. M.; Morfill, G. E.

    2008-09-01

    3D plasma clusters (up to 100 particles) have been built inside small (32 mm3) plasma volume in gravity. It has been estimated that the external confinement has a negligible influence on the processes inside the clusters. At such conditions the analysis of dynamical evolution and individual particle interactions have shown that the binary interaction among particles in addition to the repelling Coulomb force exhibits also an attractive part. The tendency of the systems to approach the state with minimum energy by rearranging particles inside has been detected. The measured 63 particles' cluster vibrations are in close agreement with vibrations of a drop with surface tension. This indicates that even a 63 particle cluster already exhibits properties normally associated with the cooperative regime.

  4. In-chip fabrication of free-form 3D constructs for directed cell migration analysis.

    PubMed

    Olsen, Mark Holm; Hjortø, Gertrud Malene; Hansen, Morten; Met, Özcan; Svane, Inge Marie; Larsen, Niels B

    2013-12-21

    Free-form constructs with three-dimensional (3D) microporosity were fabricated by two-photon polymerization inside the closed microchannel of an injection-molded, commercially available polymer chip for analysis of directed cell migration. Acrylate constructs were produced as woodpile topologies with a range of pore sizes from 5 × 5 μm to 15 × 15 μm and prefilled with fibrillar collagen. Dendritic cells seeded into the polymer chip in a concentration gradient of the chemoattractant CCL21 efficiently negotiated the microporous maze structure for pore sizes of 8 × 8 μm or larger. The cells migrating through smaller pore sizes made significantly more turns than those through larger pores. The introduction of additional defined barriers in the microporous structure resulted in dendritic cells making more turns while still being able to follow the chemoattractant concentration gradient.

  5. Noise analysis for near field 3-D FM-CW radar imaging systems

    SciTech Connect

    Sheen, David M.

    2015-06-19

    Near field radar imaging systems are used for several applications including concealed weapon detection in airports and other high-security venues. Despite the near-field operation, phase noise and thermal noise can limit the performance in several ways including reduction in system sensitivity and reduction of image dynamic range. In this paper, the effects of thermal noise, phase noise, and processing gain are analyzed in the context of a near field 3-D FM-CW imaging radar as might be used for concealed weapon detection. In addition to traditional frequency domain analysis, a time-domain simulation is employed to graphically demonstrate the effect of these noise sources on a fast-chirping FM-CW system.

  6. Lightning strike simulation using coaxial line technique and 3D linear injection current analysis

    NASA Astrophysics Data System (ADS)

    Flourens, F.; Gauthier, D.; Serafin, D.

    1989-09-01

    The GORFFD code for determining aircraft responses to either a lightning event or to simulated current injection is based on the finite-difference solution of Maxwell's equation, and allows the simulation of complex, 3D metallic and dielectric composite structures. A transfer method is used to analyze the EM environment associated with in-flight measurements. Attention is given to a linear-analysis numerical model in which the lightning channel is simulated as a thin wire that is driven by a current source. Surface E-fields and current mappings are produced for the Transall transport and Mirage fighter aircraft. An experimental method has been devised for verification of these lightning-strike simulations.

  7. 3dLOGO: a web server for the identification, analysis and use of conserved protein substructures.

    PubMed

    Via, Allegra; Peluso, Daniele; Gherardini, Pier Federico; de Rinaldis, Emanuele; Colombo, Teresa; Ausiello, Gabriele; Helmer-Citterich, Manuela

    2007-07-01

    3dLOGO is a web server for the identification and analysis of conserved protein 3D substructures. Given a set of residues in a PDB (Protein Data Bank) chain, the server detects the matching substructure(s) in a set of user-provided protein structures, generates a multiple structure alignment centered on the input substructures and highlights other residues whose structural conservation becomes evident after the defined superposition. Conserved residues are proposed to the user for highlighting functional areas, deriving refined structural motifs or building sequence patterns. Residue structural conservation can be visualized through an expressly designed Java application, 3dProLogo, which is a 3D implementation of a sequence logo. The 3dLOGO server, with related documentation, is available at http://3dlogo.uniroma2.it/ PMID:17488847

  8. Thoracic Cavity Definition for 3D PET/CT Analysis and Visualization

    PubMed Central

    Cheirsilp, Ronnarit; Bascom, Rebecca; Allen, Thomas W.; Higgins, William E.

    2015-01-01

    X-ray computed tomography (CT) and positron emission tomography (PET) serve as the standard imaging modalities for lung-cancer management. CT gives anatomical detail on diagnostic regions of interest (ROIs), while PET gives highly specific functional information. During the lung-cancer management process, a patient receives a co-registered whole-body PET/CT scan pair and a dedicated high-resolution chest CT scan. With these data, multimodal PET/CT ROI information can be gleaned to facilitate disease management. Effective image segmentation of the thoracic cavity, however, is needed to focus attention on the central chest. We present an automatic method for thoracic cavity segmentation from 3D CT scans. We then demonstrate how the method facilitates 3D ROI localization and visualization in patient multimodal imaging studies. Our segmentation method draws upon digital topological and morphological operations, active-contour analysis, and key organ landmarks. Using a large patient database, the method showed high agreement to ground-truth regions, with a mean coverage = 99.2% and leakage = 0.52%. Furthermore, it enabled extremely fast computation. For PET/CT lesion analysis, the segmentation method reduced ROI search space by 97.7% for a whole-body scan, or nearly 3 times greater than that achieved by a lung mask. Despite this reduction, we achieved 100% true-positive ROI detection, while also reducing the false-positive (FP) detection rate by >5 times over that achieved with a lung mask. Finally, the method greatly improved PET/CT visualization by eliminating false PET-avid obscurations arising from the heart, bones, and liver. In particular, PET MIP views and fused PET/CT renderings depicted unprecedented clarity of the lesions and neighboring anatomical structures truly relevant to lung-cancer assessment. PMID:25957746

  9. A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone

    PubMed Central

    Fan, Lixia; Pei, Shaopeng; Lucas Lu, X; Wang, Liyun

    2016-01-01

    The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in

  10. Evaluation of 3D multimodality image registration using receiver operating characteristic (ROC) analysis

    NASA Astrophysics Data System (ADS)

    Holton Tainter, Kerrie S.; Robb, Richard A.; Taneja, Udita; Gray, Joel E.

    1995-04-01

    Receiver operating characteristic analysis has evolved as a useful method for evaluating the discriminatory capability and efficacy of visualization. The ability of such analysis to account for the variance in decision criteria of multiple observers, multiple reading, and a wide range of difficulty in detection among case studies makes ROC especially useful for interpreting the results of a viewing experiment. We are currently using ROC analysis to evaluate the effectiveness of using fused multispectral, or complementary multimodality imaging data in the diagnostic process. The use of multispectral image recordings, gathered from multiple imaging modalities, to provide advanced image visualization and quantization capabilities in evaluating medical images is an important challenge facing medical imaging scientists. Such capabilities would potentially significantly enhance the ability of clinicians to extract scientific and diagnostic information from images. a first step in the effective use of multispectral information is the spatial registration of complementary image datasets so that a point-to-point correspondence exists between them. We are developing a paradigm of measuring the accuracy of existing image registration techniques which includes the ability to relate quantitative measurements, taken from the images themselves, to the decisions made by observers about the state of registration (SOR) of the 3D images. We have used ROC analysis to evaluate the ability of observers to discriminate between correctly registered and incorrectly registered multimodality fused images. We believe this experience is original and represents the first time that ROC analysis has been used to evaluate registered/fused images. We have simulated low-resolution and high-resolution images from real patient MR images of the brain, and fused them with the original MR to produce colorwash superposition images whose exact SOR is known. We have also attempted to extend this analysis to

  11. 3D structure determination of protein using TEM single particle analysis.

    PubMed

    Sato, Chikara; Mio, Kazuhiro; Kawata, Masaaki; Ogura, Toshihiko

    2014-11-01

    Proteins play important roles in cell functions such as enzymes, cell trafficking, neurotransmission, muscle contraction and hormone secretion. However, some proteins are very difficult to be crystallized and their structures are undetermined. Several techniques have been developed to elucidate the structure of macromolecules; X-ray or electron crystallography, nuclear magnetic resonance spectroscopy, and high-resolution electron microscopy. Among them, electron microscopy based single particle reconstruction (SPA) technique is a computer-aided structure determination method. This method reconstructs the 3D structure from projection images of dispersed protein. A large number of two-dimensional particle images are picked up from EM films, aligned and classified to generate 2D averages, and used to reconstruct the 3D structure by assigning the Euler angle of each 2D average. Due to the necessity of elaborate collaboration between the classical biology and the innovative information technology including parallel computing, scientists needed to break unseen barriers to get a start of this analysis. However, recent progresses in electron microscopes, mathematical algorithms, and computational abilities greatly reduced the height of barriers and expanded targets that are considered to be primarily addressable using single particle analysis. Membrane proteins are one of these targets to which the single particle analysis is successfully applied for the understanding of their 3D structures. For this purpose, we have developed various SPA methods [1-5] and applied them to different proteins [6-8].Here, we introduce reconstructed proteins, and discuss the availability of this technique. The intramembrane-cleaving proteases (I-CLiPs) that sever the transmembrane domains of their substrates have been identified in a range of organisms and play a variety of roles in biological conditions. I-CLiPs have been classified into three groups: serine-, aspartyl- and metalloprotease

  12. 3D combinational curves for accuracy and performance analysis of positive biometrics identification

    NASA Astrophysics Data System (ADS)

    Du, Yingzi; Chang, Chein-I.

    2008-06-01

    The receiver operating characteristic (ROC) curve has been widely used as an evaluation criterion to measure the accuracy of biometrics system. Unfortunately, such an ROC curve provides no indication of the optimum threshold and cost function. In this paper, two kinds of 3D combinational curves are proposed: the 3D combinational accuracy curve and the 3D combinational performance curve. The 3D combinational accuracy curve gives a balanced view of the relationships among FAR (false alarm rate), FRR (false rejection rate), threshold t, and Cost. Six 2D curves can be derived from the 3D combinational accuracy curve: the conventional 2D ROC curve, 2D curve of (FRR, t), 2D curve of (FAR, t), 2D curve of (FRR, Cost), 2D curve of (FAR, Cost), and 2D curve of ( t, Cost). The 3D combinational performance curve can be derived from the 3D combinational accuracy curve which can give a balanced view among Security, Convenience, threshold t, and Cost. The advantages of using the proposed 3D combinational curves are demonstrated by iris recognition systems where the experimental results show that the proposed 3D combinational curves can provide more comprehensive information of the system accuracy and performance.

  13. QSAR modeling and molecular interaction analysis of natural compounds as potent neuraminidase inhibitors.

    PubMed

    Sun, Jiaying; Mei, Hu

    2016-04-26

    Different QSAR models of 40 natural compounds as neuraminidase inhibitors (NIs) are developed to comprehend chemical-biological interactions and predict activities against neuraminidase (NA) from Clostridium perfringens. Based on the constitutional, topological and conformational descriptors, R(2) and Q(2) values of the obtained SRA model are 0.931 and 0.856. The R(2) and Q(2) values of the constructed HQSAR and almond models are 0.903 and 0.767, 0.904 and 0.511, respectively. Based on the pharmacophore alignment, R(2) and Q(2) values of the optimal CoMSIA model are 0.936 and 0.654. Moreover, Rtest(2) and Qext(2) of values of SRA, HQSAR, almond and CoMSIA models are 0.611 and 0.565, 0.753 and 0.750, 0.612 and 0.582, 0.582 and 0.571, respectively. So, QSAR models have good predictive capability. They can be further used to evaluate and screen new compounds. Moreover, hydrogen bonds and electrostatic factors have high contributions to activities. To understand molecular interactions between natural compounds and NA from Clostridium perfringens, molecular docking is investigated. The docking results elucidate that Arg266, Asp291, Asp328, Tyr485, Glu493, Arg555, Arg615 and Tyr655 are especially the key residues in the active site of 2bf6. Hydrogen bonds and electrostatics are key factors, which impact the interactions between NIs and NA. So, the influential factors of interactions between NIs and NA in the docking results are in agreement with the QSAR results. PMID:27008437

  14. A quantitative structure activity relationships (QSAR) analysis of triarylmethane dye tracers

    NASA Astrophysics Data System (ADS)

    Mon, Jarai; Flury, Markus; Harsh, James B.

    2006-01-01

    Dyes are important hydrological tracers. Many different dyes have been proposed as optimal tracers, but none of these dyes can be considered an ideal water tracer. Some dyes are toxic and most sorb to subsurface materials. The objective of this study was to find the molecular structure of an optimal water tracer. We used QSAR to screen a large number of hypothetical molecules, belonging to the class of triarylmethane dyes, in regard to their sorption characteristics to a sandy soil. The QSAR model was based on experimental sorption data obtained from four triarylmethane dyes: C.I. Food Blue 2 (C.I. 42090; Brilliant Blue FCF), C.I. Food Green 3 (C.I. 42053; FD&C Green No. 3), C.I. Acid Blue 7 (C.I. 42080; ORCOacid Blue A 150%), and C.I. Acid Green 9 (C.I. 42100; ORCOacid Fast Green B). Sorption characteristics of the dyes to the sandy soil were expressed with the Langmuir isotherm. Our premise was that dye sorption can be reduced by attachment of sulfonic acid (SO 3) groups to the triarylmethane template. About 70 hypothetical dyes were created and QSAR were used to estimate sorption characteristics. The results indicated that both the position and the number of SO 3 groups affected dye sorption. Sorption decreased with increasing number of SO 3 groups attached to the molecule. Increasing the number of sulfonic acid groups also decreases the toxicity of the compounds. An optimal triarylmethane water tracer contains 4 to 6 SO 3 groups.

  15. surf3d: A 3-D finite-element program for the analysis of surface and corner cracks in solids subjected to mode-1 loadings

    NASA Technical Reports Server (NTRS)

    Raju, I. S.; Newman, J. C., Jr.

    1993-01-01

    A computer program, surf3d, that uses the 3D finite-element method to calculate the stress-intensity factors for surface, corner, and embedded cracks in finite-thickness plates with and without circular holes, was developed. The cracks are assumed to be either elliptic or part eliptic in shape. The computer program uses eight-noded hexahedral elements to model the solid. The program uses a skyline storage and solver. The stress-intensity factors are evaluated using the force method, the crack-opening displacement method, and the 3-D virtual crack closure methods. In the manual the input to and the output of the surf3d program are described. This manual also demonstrates the use of the program and describes the calculation of the stress-intensity factors. Several examples with sample data files are included with the manual. To facilitate modeling of the user's crack configuration and loading, a companion program (a preprocessor program) that generates the data for the surf3d called gensurf was also developed. The gensurf program is a three dimensional mesh generator program that requires minimal input and that builds a complete data file for surf3d. The program surf3d is operational on Unix machines such as CRAY Y-MP, CRAY-2, and Convex C-220.

  16. Earth Science Research Discovery, Integration, 3D Visualization and Analysis using NASA World Wind

    NASA Astrophysics Data System (ADS)

    Alameh, N.; Hogan, P.

    2008-12-01

    more possible to include virtual globe capability in support of any Earth science objective. 3- With the source code being fully accessible, anyone can advance this technology (including in a commercial or other proprietary manner). Such features enable World Wind to provide easy discovery, access and 3D integration/visualization/analysis of Earth observation data in a flexible, customizable open source tool. This positions World Wind to become a key part of an Advanced Information Systems infrastructure supporting a collaborative decision-making environment for a variety of applications.

  17. 3-D MT modelling and HMT analysis for the north-west part of Poland

    NASA Astrophysics Data System (ADS)

    Ślęzak, Katarzyna; Brasse, Heinrich; Jóźwiak, Waldemar; Nowożyński, Krzysztof

    2014-05-01

    The area covered by magnetotelluric survey is a part of the Trans-European Suture Zone (TESZ). The TESZ is the largest tectonic boundary in Europe, extending from the British Isles through Poland to the Black Sea. Several two-dimensional (2-D) models of the electrical resistivity distribution have already been constructed for this area but it turned out that the region had a complicated, three-dimensional structure. Thus a three-dimensional (3-D) inversion model appears to be relevant and interesting to investigate. In cooperation with the Berlin Magnetotelluric Work Group several additional long-period magnetotelluric (LMT) sites were assembled in 2012 and 2013. The mesh was located in the north-west part of Poland (Pomerania region). As a result we obtained 17 new sites over the surface area of approximately of 100 km × 50 km, in addition to 9 stations set up earlier. The collected data were converted to a uniform format and the initial processing was executed. By using the latest software the transfer functions (impedances) and the ellipses of the phase tensor for the sites of our mesh have been calculated. The apparent resistivities and phase responses as functions of period are calculated from the impedance components. The computer program ModEM (Egbert G.D., Kelbert A., 2012), which is used for this work, is a parallel 3-D inversion program for magnetotelluric data. The inversion code employs MPI and, besides impedances, includes tippers and magnetic tensor. The main result of this work is a 3-D model with a good RMS fit of ~2.2 which we could compare with previous outcomes. In this model two prominent, NW-SE striking conductive lineaments located in the mid-crustal levels are noticed. These structures we relate tentatively to the Variscan and Caledonian deformation fronts. Also the analysis of the invariants of the Horizontal Magnetic Tensor (HMT) obtained from previous results (Jozwiak, 2012) allowed us to examine the TESZ in more detail.

  18. Within-guild dietary discrimination from 3-D textural analysis of tooth microwear in insectivorous mammals

    PubMed Central

    Purnell, M A; Crumpton, N; Gill, P G; Jones, G; Rayfield, E J

    2013-01-01

    Resource exploitation and competition for food are important selective pressures in animal evolution. A number of recent investigations have focused on linkages between diversification, trophic morphology and diet in bats, partly because their roosting habits mean that for many bat species diet can be quantified relatively easily through faecal analysis. Dietary analysis in mammals is otherwise invasive, complicated, time consuming and expensive. Here we present evidence from insectivorous bats that analysis of three-dimensional (3-D) textures of tooth microwear using International Organization for Standardization (ISO) roughness parameters derived from sub-micron surface data provides an additional, powerful tool for investigation of trophic resource exploitation in mammals. Our approach, like scale-sensitive fractal analysis, offers considerable advantages over two-dimensional (2-D) methods of microwear analysis, including improvements in robustness, repeatability and comparability of studies. Our results constitute the first analysis of microwear textures in carnivorous mammals based on ISO roughness parameters. They demonstrate that the method is capable of dietary discrimination, even between cryptic species with subtly different diets within trophic guilds, and even when sample sizes are small. We find significant differences in microwear textures between insectivore species whose diet contains different proportions of ‘hard’ prey (such as beetles) and ‘soft’ prey (such as moths), and multivariate analyses are able to distinguish between species with different diets based solely on their tooth microwear textures. Our results show that, compared with previous 2-D analyses of microwear in bats, ISO roughness parameters provide a much more sophisticated characterization of the nature of microwear surfaces and can yield more robust and subtle dietary discrimination. ISO-based textural analysis of tooth microwear thus has a useful role to play

  19. 3D models as a platform for urban analysis and studies on human perception of space

    NASA Astrophysics Data System (ADS)

    Fisher-Gewirtzman, D.

    2012-10-01

    The objective of this work is to develop an integrated visual analysis and modelling for environmental and urban systems in respect to interior space layout and functionality. This work involves interdisciplinary research efforts that focus primarily on architecture design discipline, yet incorporates experts from other and different disciplines, such as Geoinformatics, computer sciences and environment-behavior studies. This work integrates an advanced Spatial Openness Index (SOI) model within realistic geovisualized Geographical Information System (GIS) environment and assessment using subjective residents' evaluation. The advanced SOI model measures the volume of visible space at any required view point practically, for every room or function. This model enables accurate 3D simulation of the built environment regarding built structure and surrounding vegetation. This paper demonstrates the work on a case study. A 3D model of Neve-Shaanan neighbourhood in Haifa was developed. Students that live in this neighbourhood had participated in this research. Their apartments were modelled in details and inserted into a general model, representing topography and the volumes of buildings. The visual space for each room in every apartment was documented and measured and at the same time the students were asked to answer questions regarding their perception of space and view from their residence. The results of this research work had shown potential contribution to professional users, such as researchers, designers and city planners. This model can be easily used by professionals and by non-professionals such as city dwellers, contractors and developers. This work continues with additional case studies having different building typologies and functions variety, using virtual reality tools.

  20. Prospective in (Primate) Dental Analysis through Tooth 3D Topographical Quantification

    PubMed Central

    Guy, Franck; Gouvard, Florent; Boistel, Renaud; Euriat, Adelaïde; Lazzari, Vincent

    2013-01-01

    The occlusal morphology of the teeth is mostly determined by the enamel-dentine junction morphology; the enamel-dentine junction plays the role of a primer and conditions the formation of the occlusal enamel reliefs. However, the accretion of the enamel cap yields thickness variations that alter the morphology and the topography of the enamel–dentine junction (i.e., the differential deposition of enamel by the ameloblasts create an external surface that does not necessarily perfectly parallel the enamel–dentine junction). This self-reliant influence of the enamel on tooth morphology is poorly understood and still under-investigated. Studies considering the relationship between enamel and dentine morphologies are rare, and none of them tackled this relationship in a quantitative way. Major limitations arose from: (1) the difficulties to characterize the tooth morphology in its comprehensive tridimensional aspect and (2) practical issues in relating enamel and enamel–dentine junction quantitative traits. We present new aspects of form representation based exclusively on 3D analytical tools and procedures. Our method is applied to a set of 21 unworn upper second molars belonging to eight extant anthropoid genera. Using geometrical analysis of polygonal meshes representatives of the tooth form, we propose a 3D dataset that constitutes a detailed characterization of the enamel and of the enamel–dentine junction morphologies. Also, for the first time, to our knowledge, we intend to establish a quantitative method for comparing enamel and enamel–dentine junction surfaces descriptors (elevation, inclination, orientation, etc.). New indices that allow characterizing the occlusal morphology are proposed and discussed. In this note, we present technical aspects of our method with the example of anthropoid molars. First results show notable individual variations and taxonomic heterogeneities for the selected topographic parameters and for the pattern and strength of

  1. Analysis of hybrid dielectric-plasmonic slot waveguide structures with 3D Fourier Modal Methods

    NASA Astrophysics Data System (ADS)

    Ctyroky, J.; Kwiecien, P.; Richter, I.

    2013-03-01

    Recently, plasmonic waveguides have been intensively studied as promising basic building blocks for the construction of extremely compact photonic devices with subwavelength characteristic dimensions. A number of different types of plasmonic waveguide structures have been recently proposed, theoretically analyzed, and their properties experimentally verified. The fundamental trade-off in the design of plasmonic waveguides for potential application in information technologies lies in the contradiction between their mode field confinement and propagation loss: the higher confinement, the higher loss, and vice versa. Various definitions of figures of merit of plasmonic waveguides have been also introduced for the characterization of their properties with a single quantity. In this contribution, we theoretically analyze one specific type of a plasmonic waveguide - the hybrid dielectric-loaded plasmonic waveguide, or - as we call it in this paper - the hybrid dielectric-plasmonic slot waveguide, which exhibits very strong field confinement combined with acceptable losses allowing their application in some integrated plasmonic devices. In contrast to the structures analyzed previously, our structure makes use of a single low-index dielectric only. We first define the effective area of this waveguide type, and using waveguide parameters close to the optimum we analyze several waveguide devices as directional couplers, multimode interference couplers (MMI), and the Mach-Zehnder interferometer based on the MMI couplers. For the full-vector 3D analysis of these structures, we use modelling tools developed in-house on the basis of the Fourier Modal Method (FMM). Our results thus serve to a dual purpose: they confirm that (i) these structures represent promising building blocks of plasmonic devices, and (ii) our FMM codes are capable of efficient 3D vector modelling of plasmonic waveguide devices.

  2. Prostate volume contouring: A 3D analysis of segmentation using 3DTRUS, CT, and MR

    SciTech Connect

    Smith, Wendy L. . E-mail: wendy.smith@cancerboard.ab.ca; Lewis, Craig |; Bauman, Glenn ||; Rodrigues, George ||; D'Souza, David |; Ash, Robert |; Ho, Derek; Venkatesan, Varagur |; Downey, Donal; Fenster, Aaron

    2007-03-15

    Purpose: This study evaluated the reproducibility and modality differences of prostate contouring after brachytherapy implant using three-dimensional (3D) transrectal ultrasound (3DTRUS), T2-weighted magnetic resonance (MR), and computed tomography (CT) imaging. Methods and Materials: Seven blinded observers contoured 10 patients' prostates, 30 day postimplant, on 3DTRUS, MR, and CT images to assess interobserver variability. Randomized images were contoured twice by each observer. We analyzed length and volume measurements and performed a 3D analysis of intra- and intermodality variation. Results: Average volume ratios were 1.16 for CT/MR, 0.90 for 3DTRUS/MR, and 1.30 for CT/3DTRUS. Overall contouring variability was largest for CT and similar for MR and 3DTRUS. The greatest variability of CT contours occurred at the posterior and anterior portions of the midgland. On MR, overall variability was smaller, with a maximum in the anterior region. On 3DTRUS, high variability occurred in anterior regions of the apex and base, whereas the prostate-rectum interface had the smallest variability. The shape of the prostate on MR was rounder, with the base and apex of similar size, whereas CT contours had broad, flat bases narrowing toward the apex. The average percent of surface area that was significantly different (95% confidence interval) for CT/MR was 4.1%; 3DTRUS/MR, 10.7%; and CT/3DTRUS, 6.3%. The larger variability of CT measurements made significant differences more difficult to detect. Conclusions: The contouring of prostates on CT, MR, and 3DTRUS results in systematic differences in the locations of and variability in prostate boundary definition between modalities. MR and 3DTRUS display the smallest variability and the closest correspondence.

  3. Finite Element Analysis of Mechanical Properties of 3D Four-directional Rectangular Braided Composites—Part 2: Validation of the 3D Finite Element Model

    NASA Astrophysics Data System (ADS)

    Li, Dian-Sen; Fang, Dai-Ning; Lu, Zi-Xing; Yang, Zhen-Yu; Jiang, Nan

    2010-08-01

    In the first part of the work, we have established a new parameterized three-dimensional (3D) finite element model (FEM) which precisely simulated the spatial configuration of the braiding yarns and considered the cross-section deformation as well as the surface contact relationship between the yarns. This paper presents a prediction of the effective elastic properties and the meso-scale mechanical response of 3D braided composites to verify the validation of the FEM. The effects of the braiding parameters on the mechanical properties are investigated in detail. By analyzing the deformation and stress nephogram of the model, a reasonable overall stress field is provided and the results well support the strength prediction. The results indicate it is convenient to predict all the elastic constants of 3D braided composites with different parameters simultaneously using the FEM. Moreover, the FEM can successfully predict the meso-scale mechanical response of 3D braided composites containing periodical structures.

  4. Rigorous 3-D coupled wave diffraction analysis of multiple superposed gratings in anisotropic media.

    PubMed

    Glytsis, E N; Gaylord, T K

    1989-06-15

    The diffraction by two planar slanted fringe gratings superposed in the same volume of an anisotropic medium is treated using rigorous 3-D vector coupled wave analysis. Arbitrary angle of incidence and polarization are included. Both phase and/or amplitude slanted gratings in anisotropic media are treated in the analysis. The external boundary regions can be either isotropic (for bulk applications) or uniaxial anisotropic (for integrated applications). Both forward- and backward-diffracted orders are characterized by a number pair (i(l),i(2)), where i(l) and i(2) are integers. The Floquet condition is discussed for the case of two superposed gratings. When the external regions are anisotropic, each diffracted order has an ordinary (O), and an extraordinary (E) component. The analysis is also generalized for an arbitrary number of superposed gratings. The numerical complexity is discussed. In the case of equal grating periodicities along the boundaries, the diffracted orders become degenerate in the external regions. In this case, an alternative analysis that utilizes a cascaded stack of unslanted gratings can be used. Limiting cases are also presented. The various Bragg conditions are identified and quantified. Sample calculations presented include the quantification of the crosstalk between two superposed gratings, the evaluation of the effects of coupled Bragg conditions in beam combining applications, design and analysis of a beam splitter and a beam combiner, demonstration of the use of a cascaded stack of unslanted gratings of constant modulation to represent two superposed gratings that have the same periodicity along the boundaries, and finally evaluation of the effect of the phase difference between two gratings. The same analysis applies in the limiting cases of isotropic materials, single slanted gratings, etc. Applications of this analysis include optical storage, optical digital truth table look-up processing, neural nets, optical interconnects, beam

  5. Earthscape, a Multi-Purpose Interactive 3d Globe Viewer for Hybrid Data Visualization and Analysis

    NASA Astrophysics Data System (ADS)

    Sarthou, A.; Mas, S.; Jacquin, M.; Moreno, N.; Salamon, A.

    2015-08-01

    The hybrid visualization and interaction tool EarthScape is presented here. The software is able to display simultaneously LiDAR point clouds, draped videos with moving footprint, volume scientific data (using volume rendering, isosurface and slice plane), raster data such as still satellite images, vector data and 3D models such as buildings or vehicles. The application runs on touch screen devices such as tablets. The software is based on open source libraries, such as OpenSceneGraph, osgEarth and OpenCV, and shader programming is used to implement volume rendering of scientific data. The next goal of EarthScape is to perform data analysis using ENVI Services Engine, a cloud data analysis solution. EarthScape is also designed to be a client of Jagwire which provides multisource geo-referenced video fluxes. When all these components will be included, EarthScape will be a multi-purpose platform that will provide at the same time data analysis, hybrid visualization and complex interactions. The software is available on demand for free at france@exelisvis.com.

  6. Development of Non-LOCA Safety Analysis Methodology with RETRAN-3D and VIPRE-01/K

    SciTech Connect

    Kim, Yo-Han; Cheong, Ae-Ju; Yang, Chang-Keun

    2004-10-15

    Korea Electric Power Research Institute has launched a project to develop an in-house non-loss-of-coolant-accident analysis methodology to overcome the hardships caused by the narrow analytical scopes of existing methodologies. Prior to the development, some safety analysis codes were reviewed, and RETRAN-3D and VIPRE-01 were chosen as the base codes. The codes have been modified to improve the analytical capabilities required to analyze the nuclear power plants in Korea. The methodologies of the vendors and the Electric Power Research Institute have been reviewed, and some documents of foreign utilities have been used to compensate for the insufficiencies. For the next step, a draft methodology for pressurized water reactors has been developed and modified to apply to Westinghouse-type plants in Korea. To verify the feasibility of the methodology, some events of Yonggwang Units 1 and 2 have been analyzed from the standpoints of reactor coolant system pressure and the departure from nucleate boiling ratio. The results of the analyses show trends similar to those of the Final Safety Analysis Report.

  7. Analysis of simple 2-D and 3-D metal structures subjected to fragment impact

    NASA Technical Reports Server (NTRS)

    Witmer, E. A.; Stagliano, T. R.; Spilker, R. L.; Rodal, J. J. A.

    1977-01-01

    Theoretical methods were developed for predicting the large-deflection elastic-plastic transient structural responses of metal containment or deflector (C/D) structures to cope with rotor burst fragment impact attack. For two-dimensional C/D structures both, finite element and finite difference analysis methods were employed to analyze structural response produced by either prescribed transient loads or fragment impact. For the latter category, two time-wise step-by-step analysis procedures were devised to predict the structural responses resulting from a succession of fragment impacts: the collision force method (CFM) which utilizes an approximate prediction of the force applied to the attacked structure during fragment impact, and the collision imparted velocity method (CIVM) in which the impact-induced velocity increment acquired by a region of the impacted structure near the impact point is computed. The merits and limitations of these approaches are discussed. For the analysis of 3-d responses of C/D structures, only the CIVM approach was investigated.

  8. SCEC/CME CyberShake: Probabilistic Seismic Hazard Analysis Using 3D Seismic Waveform Modeling

    NASA Astrophysics Data System (ADS)

    Callaghan, S.; Maechling, P. J.; Cui, Y.; Faerman, M.; Field, E.; Graves, R.; Gupta, N.; Gupta, V.; Jordan, T. H.; Kesselman, C.; Mehta, G.; Okaya, D.; Vahi, K.; Zhao, L.

    2005-12-01

    Researchers on the SCEC Community Modeling Environment (SCEC/CME) Project are calculating Probabilistic Seismic Hazard Curves for several sites in the Los Angeles area. The hazard curves calculated in this study use Intensity Measure Relationships (IMRs) based on 3D ground motion simulations rather than on attenuation relationships. State-of-the-art Probabilistic Seismic Hazard Analysis (PSHA) is currently conducted using IMRs that use empirically-based attenuation relationships. These attenuation relationships represent relatively simple analytical models based on the regression of observed data. However, it is widely believed that significant improvements in SHA will rely on the use of more physics-based, waveform modeling. In fact, a more physics-based approach to PSHA was endorsed in a recent assessment of earthquake science by National Research Council (2003). In order to introduce the use of 3D seismic waveform modeling into PSHA hazard curve calculations, the SCEC/CME CyberShake group is integrating state-of-the-art PSHA software tools (OpenSHA), SCEC-developed geophysical models (SCEC CVM3.0), validated anelastic wave modeling (AWM) software, and state-of-the-art computational technologies including high performance computing and grid-based scientific workflows in an effort to develop an OpenSHA-compatible 3D waveform-based IMR component. This will allow researchers to combine a new class of waveform-based IMRs with the large number of existing PSHA components, such as Earthquake Rupture Forecasts (ERF's), that are currently implemented in the OpenSHA system. To calculate a probabilistic hazard curve for a site of interest, we use the OpenSHA implementation of the NSHMP-2002 ERF and identify all ruptures within 200km of the site of interest. For each of these ruptures, we convert the NSHMP-2002 rupture definition into one, or more, Ruptures with Slip Time History (Rupture Variations) using newly developed Rupture Generator software. Strain Green Tensors are

  9. QSAR Study on Thiazolidine-2,4-dione Derivatives for Antihyperglycemic Activity.

    PubMed

    Prashantha Kumar, B R; Nanjan, M J

    2008-09-01

    A set of seventy four molecules belonging to the class of thioglitazones were subjected to the QSAR analysis for their antihyperglycemic activity. All the molecules were subjected to energy minimization to get 3D structures, followed by conformational analysis to get the conformation of the molecule associated with the least energy and highest stability. Various physico-chemical parameters were then calculated using ALCHEMY 2000 software, namely, thermodynamic parameters, structure-dependant parameters, topological parameters and charge-dependant parameters. Multiple linear regression analysis was carried out on all the molecules. The final equation was developed by choosing optimal combination of descriptors after removing the outliers. Cross validation was performed by leave one out method to arrive at the final QSAR model for the chosen set of molecules to exhibit antihyperglycemic activity. PMID:21394250

  10. QSAR Study on Thiazolidine-2,4-dione Derivatives for Antihyperglycemic Activity

    PubMed Central

    Prashantha Kumar, B. R.; Nanjan, M. J.

    2008-01-01

    A set of seventy four molecules belonging to the class of thioglitazones were subjected to the QSAR analysis for their antihyperglycemic activity. All the molecules were subjected to energy minimization to get 3D structures, followed by conformational analysis to get the conformation of the molecule associated with the least energy and highest stability. Various physico-chemical parameters were then calculated using ALCHEMY 2000 software, namely, thermodynamic parameters, structure-dependant parameters, topological parameters and charge-dependant parameters. Multiple linear regression analysis was carried out on all the molecules. The final equation was developed by choosing optimal combination of descriptors after removing the outliers. Cross validation was performed by leave one out method to arrive at the final QSAR model for the chosen set of molecules to exhibit antihyperglycemic activity. PMID:21394250

  11. Analysis of the KROTOS KFC test by coupling X-Ray image analysis and MC3D calculations

    SciTech Connect

    Brayer, C.; Charton, A.; Grishchenko, D.; Fouquart, P.; Bullado, Y.; Compagnon, F.; Correggio, P.; Cassiaut-Louis, N.; Piluso, P.

    2012-07-01

    During a hypothetical severe accident sequence in a Pressurized Water Reactor (PWR), the hot molten materials (corium) issuing from the degraded reactor core may generate a steam explosion if they come in contact with water and may damage the structures and threaten the reactor integrity. The SERENA program is an international OECD project that aims at helping the understanding of this phenomenon also called Fuel Coolant Interaction (FCI) by providing data. CEA takes part in this program by performing tests in its KROTOS facility where steam explosions using prototypic corium can be triggered. Data about the different phases in the premixing are extracted from the KROTOS X-Ray radioscopy images by using KIWI software (KROTOS Image analysis of Water-corium Interaction) currently developed by CEA. The MC3D code, developed by IRSN, is a thermal-hydraulic multiphase code mainly dedicated to FCI studies. It is composed of two applications: premixing and explosion. An overall FCI calculation with MC3D requires a premixing calculation followed by an explosion calculation. The present paper proposes an alternative approach in which all the features of the premixing are extracted from the X-Ray pictures using the KIWI software and transferred to an MC3D dataset for a direct simulation of the explosion. The main hypothesis are discussed as well as the first explosion results obtained with MC3D for the KROTOS KFC test. These results are rather encouraging and are analyzed on the basis of comparisons with the experimental data. (authors)

  12. The MHOST finite element program: 3-D inelastic analysis methods for hot section components. Volume 2: User's manual

    NASA Technical Reports Server (NTRS)

    Nakazawa, Shohei

    1989-01-01

    The user options available for running the MHOST finite element analysis package is described. MHOST is a solid and structural analysis program based on the mixed finite element technology, and is specifically designed for 3-D inelastic analysis. A family of 2- and 3-D continuum elements along with beam and shell structural elements can be utilized, many options are available in the constitutive equation library, the solution algorithms and the analysis capabilities. The outline of solution algorithms is discussed along with the data input and output, analysis options including the user subroutines and the definition of the finite elements implemented in the program package.

  13. Latest developments and opportunities for 3D analysis of biological samples by confocal μ-XRF

    NASA Astrophysics Data System (ADS)

    Perez, Roberto D.; Sánchez, Héctor J.; Perez, Carlos A.; Rubio, Marcelo

    2010-02-01

    X-ray fluorescence analysis performed with a primary radiation focused in the micrometer range is known as micro-X-ray fluorescence (μ-XRF). It is characterized by a penetration depth higher than other micro-analytical methods, reaching hundreds of micrometers in biological samples. This characteristic of the X-ray beam can be employed in 3D analysis. An innovative method to perform 3D analysis by μ-XRF is the so-called confocal setup. The confocal setup consists of X-ray lenses in the excitation as well as in the detection channel. In this configuration, a micro-volume defined by the overlap of the foci of both X-ray lenses is analyzed. Scanning this micro-volume through the sample can be used to perform a study in three dimensions. At present, X-ray lenses used in confocal μ-XRF experiments are mainly glass capillaries and polycapillaries. Glass capillaries are used in the excitation channel with sources of high photon flux like synchrotron radiation. Half polycapillaries or conical polycapillary concentrators are used almost exclusively in the detection channel. Spatial resolution of the confocal μ-XRF depends on the dimensions of the foci of both X-ray lenses. The overlap of these foci forms an ellipsoid which is the probing volume of the confocal setup. The axis length of the probing volume reported in confocal μ-XRF experiments are of order of few tens of micrometer. In our confocal setup, we used a commercial glass monocapillary in the excitation channel and a monolithic half polycapillary in the detection channel. The polycapillary was home-made by means of drawing of multibundles of glass capillaries in a heating furnace. The experiment was carried out at the beamline D09B-XRF of the Synchrotron Light National Laboratory (Laboratório Nacional de Luz Síncrotron, LNLS) using white beam. A model for the theoretical description of X-ray fluorescence intensity registered by confocal μ-XRF was introduced by Malzer and Kanngieβer [2005. A model for the

  14. Segmentation of vascular structures and hematopoietic cells in 3D microscopy images and quantitative analysis

    NASA Astrophysics Data System (ADS)

    Mu, Jian; Yang, Lin; Kamocka, Malgorzata M.; Zollman, Amy L.; Carlesso, Nadia; Chen, Danny Z.

    2015-03-01

    In this paper, we present image processing methods for quantitative study of how the bone marrow microenvironment changes (characterized by altered vascular structure and hematopoietic cell distribution) caused by diseases or various factors. We develop algorithms that automatically segment vascular structures and hematopoietic cells in 3-D microscopy images, perform quantitative analysis of the properties of the segmented vascular structures and cells, and examine how such properties change. In processing images, we apply local thresholding to segment vessels, and add post-processing steps to deal with imaging artifacts. We propose an improved watershed algorithm that relies on both intensity and shape information and can separate multiple overlapping cells better than common watershed methods. We then quantitatively compute various features of the vascular structures and hematopoietic cells, such as the branches and sizes of vessels and the distribution of cells. In analyzing vascular properties, we provide algorithms for pruning fake vessel segments and branches based on vessel skeletons. Our algorithms can segment vascular structures and hematopoietic cells with good quality. We use our methods to quantitatively examine the changes in the bone marrow microenvironment caused by the deletion of Notch pathway. Our quantitative analysis reveals property changes in samples with deleted Notch pathway. Our tool is useful for biologists to quantitatively measure changes in the bone marrow microenvironment, for developing possible therapeutic strategies to help the bone marrow microenvironment recovery.

  15. A neural-network appearance-based 3-D object recognition using independent component analysis.

    PubMed

    Sahambi, H S; Khorasani, K

    2003-01-01

    This paper presents results on appearance-based three-dimensional (3-D) object recognition (3DOR) accomplished by utilizing a neural-network architecture developed based on independent component analysis (ICA). ICA has already been applied for face recognition in the literature with encouraging results. In this paper, we are exploring the possibility of utilizing the redundant information in the visual data to enhance the view based object recognition. The underlying premise here is that since ICA uses high-order statistics, it should in principle outperform principle component analysis (PCA), which does not utilize statistics higher than two, in the recognition task. Two databases of images captured by a CCD camera are used. It is demonstrated that ICA did perform better than PCA in one of the databases, but interestingly its performance was no better than PCA in the case of the second database. Thus, suggesting that the use of ICA may not necessarily always give better results than PCA, and that the application of ICA is highly data dependent. Various factors affecting the differences in the recognition performance using both methods are also discussed. PMID:18237997

  16. Comparative abilities of Microsoft Kinect and Vicon 3D motion capture for gait analysis.

    PubMed

    Pfister, Alexandra; West, Alexandre M; Bronner, Shaw; Noah, Jack Adam

    2014-07-01

    Biomechanical analysis is a powerful tool in the evaluation of movement dysfunction in orthopaedic and neurologic populations. Three-dimensional (3D) motion capture systems are widely used, accurate systems, but are costly and not available in many clinical settings. The Microsoft Kinect™ has the potential to be used as an alternative low-cost motion analysis tool. The purpose of this study was to assess concurrent validity of the Kinect™ with Brekel Kinect software in comparison to Vicon Nexus during sagittal plane gait kinematics. Twenty healthy adults (nine male, 11 female) were tracked while walking and jogging at three velocities on a treadmill. Concurrent hip and knee peak flexion and extension and stride timing measurements were compared between Vicon and Kinect™. Although Kinect measurements were representative of normal gait, the Kinect™ generally under-estimated joint flexion and over-estimated extension. Kinect™ and Vicon hip angular displacement correlation was very low and error was large. Kinect™ knee measurements were somewhat better than hip, but were not consistent enough for clinical assessment. Correlation between Kinect™ and Vicon stride timing was high and error was fairly small. Variability in Kinect™ measurements was smallest at the slowest velocity. The Kinect™ has basic motion capture capabilities and with some minor adjustments will be an acceptable tool to measure stride timing, but sophisticated advances in software and hardware are necessary to improve Kinect™ sensitivity before it can be implemented for clinical use.

  17. An example of neutronic penalizations in reactivity transient analysis using 3D coupled chain HEMERA

    SciTech Connect

    Dubois, F.; Normand, B.; Sargeni, A.

    2012-07-01

    HEMERA (Highly Evolutionary Methods for Extensive Reactor Analyses), is a fully coupled 3D computational chain developed jointly by IRSN and CEA. It is composed of CRONOS2 (core neutronics, cross sections library from APOLLO2), FLICA4 (core thermal-hydraulics) and the system code CATHARE. Multi-level and multi-dimensional models are developed to account for neutronics, core thermal-hydraulics, fuel thermal analysis and system thermal-hydraulics, dedicated to best-estimate, conservative simulations and sensitivity analysis. In IRSN, the HEMERA chain is widely used to study several types of reactivity accidents and for sensitivity studies. Just as an example of the HEMERA possibilities, we present here two types of neutronic penalizations and their impact on a power transient due to a REA (Rod Ejection Accident): in the first one, we studied a bum-up distribution modification and in the second one, a delayed-neutron fraction modification. Both modifications are applied to the whole core or localized in a few assemblies. Results show that it is possible to use global or local changes but 1) in case of bum-up modification, the total core power can increase when assembly peak power decrease so, care has to be taken if the goal is to maximize a local power peak and 2) for delayed-neutron fraction, a local modification can have the same effect as the one on the whole core, provided that it is large enough. (authors)

  18. Analysis of controlling parameters for shear behavior of rock joints with FLAC3D

    NASA Astrophysics Data System (ADS)

    Tiwari, Prasoon

    The research investigation is conducted to perform an analysis of sensitivity of parameters affecting the strength of joints in rock mass. Friction angle, normal stiffness, shear stiffness and shear displacement are the parameters analyzed with respect to shear strength of rock joints. Discontinuities have an important influence on the deformational behavior of rock systems; hence, proper consideration of the physical and mechanical properties of discontinuities is necessary during experimental investigation, in order to correctly evaluate the shear behavior. These parameters are utilized to simulate the in situ stress condition in numerical modeling, which is important for safe and economical design of various engineering constructions. These concerns require accurate quantification of shear strength of unfilled and in-filled joints, proper understanding of the basic mechanics of discontinuity and the principals involved in their shear deformation. This can be achieved through laboratory testing on natural rock core samples. In the present work, the detailed account of test results of direct shear tests performed on rock joints is presented. Rock samples are obtained by core drilling in an underground mine, in Nevada. These rock samples, containing joint, are used to perform direct shear strength test. Calibration of numerical model is done on average values obtained from direct shear strength test. Analysis of sensitivity of parameters effecting shear strength of rock is done in FLAC3D shear test environment. A numerical parametric study is done, according to the Mohr-Coulomb constitutive model, and results obtained are plotted to estimate performance of rock joints.

  19. A detailed 3D finite element analysis of the peeling behaviour of a gecko spatula.

    PubMed

    Sauer, Roger A; Holl, Matthias

    2013-01-01

    This paper presents a detailed finite element analysis of the adhesion of a gecko spatula. The gecko spatulae form the tips of the gecko foot hairs that transfer the adhesional and frictional forces between substrate and foot. The analysis is based on a parameterised description of the 3D geometry of the spatula that only requires 12 parameters. The adhesion is described by a nonlinear computational contact formulation that accounts for the van der Waals interaction between spatula and substrate. The spatula adhesion model is implemented using an enriched contact finite element formulation recently developed by the first author. The finite element model is then used to simulate the peeling behaviour of the gecko spatula under applied vertical and rotational loading for various model parameters. Variations of the material stiffness, adhesional strength and range, stiction, spatula size and spatula inclination are considered to account for the natural variation of spatula properties. The study demonstrates that the spatula can function over a wide range of conditions. The computed pull-off forces are in agreement with experimental results reported in the literature. The study also examines the energy required for the spatula pull-off. The proposed model is ideal to study the influence of substrate roughness on the spatula adhesion, as is finally demonstrated.

  20. 3D geometric morphometric analysis of the proximal epiphysis of the hominoid humerus

    PubMed Central

    Arias-Martorell, Julia; Potau, Josep Maria; Bello-Hellegouarch, Gaëlle; Pastor, Juan Francisco; Pérez-Pérez, Alejandro

    2012-01-01

    In this study we perform a three-dimensional geometric morphometric (3D GM) analysis of the proximal epiphysis of the humerus in extant great apes, including humans, in order to accurately describe the functional anatomical differences between these taxa. In addition, a fossil hominin specimen of Australopithecus afarensis was included in a multivariate GM analysis in order to test the potential of this methodological approach for making locomotor inferences from fossil remains. The results obtained show significant differences in proximal humeral morphology among the taxa studied, which had thus far largely remained unnoticed. Based on morphofunctional considerations, these anatomical differences can be correlated to differences in the locomotor repertoires of the taxa, thus confirming that the proximal humerus is suitable for constructing paleobiological inferences about locomotion. Modern humans display markedly divergent features, which set them apart from both the extant great apes and the fossil hominin A. afarensis. The morphology of the proximal epiphysis of the humerus of the latter more closely resembles that of the orangutans, thus suggesting that despite hindlimb adaptations to bipedalism, the forelimb of this taxon was still functionally involved in arboreal behaviors, such as climbing or suspension. PMID:22946496

  1. Validity of a dichotomous expert response in bitemark analysis using 3-D technology.

    PubMed

    Martin-de-Las-Heras, Stella; Tafur, Daniel

    2011-03-01

    Despite efforts to quantify bitemark evidence, comparison procedures remain subjective and yield different degrees of certainty. Our aim was to study the effectiveness of a comparison procedure requiring a dichotomous response by the expert. We compared overlays from 3-D images of dental casts and bite impressions, obtained using DentalPrint(©) software. Receiver operating characteristic (ROC) analysis was performed on the results of 104 comparisons, finding an area under the ROC curve of 0.955 (standard error=0.029; 95% CI, 0.896-0.986), sensitivity of 92.3% (95% CI, 74.8-98.8) and specificity of 98.7% (95% CI, 93.0-99.8). According to these findings, this bitemark analysis procedure is highly accurate, although study limitations are discussed, placing these results in context. The main advantage of the dichotomous decision model is that it can be more easily understood, facilitating course of justice. Further research is warranted to explore the potential of this approach as an alternative to diagnostic decisions based on certainty levels. PMID:21334578

  2. Computer-Assisted 3D Kinematic Analysis of All Leg Joints in Walking Insects

    PubMed Central

    Bender, John A.; Simpson, Elaine M.; Ritzmann, Roy E.

    2010-01-01

    High-speed video can provide fine-scaled analysis of animal behavior. However, extracting behavioral data from video sequences is a time-consuming, tedious, subjective task. These issues are exacerbated where accurate behavioral descriptions require analysis of multiple points in three dimensions. We describe a new computer program written to assist a user in simultaneously extracting three-dimensional kinematics of multiple points on each of an insect's six legs. Digital video of a walking cockroach was collected in grayscale at 500 fps from two synchronized, calibrated cameras. We improved the legs' visibility by painting white dots on the joints, similar to techniques used for digitizing human motion. Compared to manual digitization of 26 points on the legs over a single, 8-second bout of walking (or 106,496 individual 3D points), our software achieved approximately 90% of the accuracy with 10% of the labor. Our experimental design reduced the complexity of the tracking problem by tethering the insect and allowing it to walk in place on a lightly oiled glass surface, but in principle, the algorithms implemented are extensible to free walking. Our software is free and open-source, written in the free language Python and including a graphical user interface for configuration and control. We encourage collaborative enhancements to make this tool both better and widely utilized. PMID:21049024

  3. BWR station blackout: A RISMC analysis using RAVEN and RELAP5-3D

    DOE PAGES

    Mandelli, D.; Smith, C.; Riley, T.; Nielsen, J.; Alfonsi, A.; Cogliati, J.; Rabiti, C.; Schroeder, J.

    2016-01-01

    The existing fleet of nuclear power plants is in the process of extending its lifetime and increasing the power generated from these plants via power uprates and improved operations. In order to evaluate the impact of these factors on the safety of the plant, the Risk-Informed Safety Margin Characterization (RISMC) project aims to provide insights to decision makers through a series of simulations of the plant dynamics for different initial conditions and accident scenarios. This paper presents a case study in order to show the capabilities of the RISMC methodology to assess impact of power uprate of a Boiling Watermore » Reactor system during a Station Black-Out accident scenario. We employ a system simulator code, RELAP5-3D, coupled with RAVEN which perform the stochastic analysis. Lastly, our analysis is performed by: 1) sampling values from a set of parameters from the uncertainty space of interest, 2) simulating the system behavior for that specific set of parameter values and 3) analyzing the outcomes from the set of simulation runs.« less

  4. BWR station blackout: A RISMC analysis using RAVEN and RELAP5-3D

    SciTech Connect

    Mandelli, D.; Smith, C.; Riley, T.; Nielsen, J.; Alfonsi, A.; Cogliati, J.; Rabiti, C.; Schroeder, J.

    2016-01-01

    The existing fleet of nuclear power plants is in the process of extending its lifetime and increasing the power generated from these plants via power uprates and improved operations. In order to evaluate the impact of these factors on the safety of the plant, the Risk-Informed Safety Margin Characterization (RISMC) project aims to provide insights to decision makers through a series of simulations of the plant dynamics for different initial conditions and accident scenarios. This paper presents a case study in order to show the capabilities of the RISMC methodology to assess impact of power uprate of a Boiling Water Reactor system during a Station Black-Out accident scenario. We employ a system simulator code, RELAP5-3D, coupled with RAVEN which perform the stochastic analysis. Lastly, our analysis is performed by: 1) sampling values from a set of parameters from the uncertainty space of interest, 2) simulating the system behavior for that specific set of parameter values and 3) analyzing the outcomes from the set of simulation runs.

  5. Quality Analysis of 3d Surface Reconstruction Using Multi-Platform Photogrammetric Systems

    NASA Astrophysics Data System (ADS)

    Lari, Z.; El-Sheimy, N.

    2016-06-01

    In recent years, the necessity of accurate 3D surface reconstruction has been more pronounced for a wide range of mapping, modelling, and monitoring applications. The 3D data for satisfying the needs of these applications can be collected using different digital imaging systems. Among them, photogrammetric systems have recently received considerable attention due to significant improvements in digital imaging sensors, emergence of new mapping platforms, and development of innovative data processing techniques. To date, a variety of techniques haven been proposed for 3D surface reconstruction using imagery collected by multi-platform photogrammetric systems. However, these approaches suffer from the lack of a well-established quality control procedure which evaluates the quality of reconstructed 3D surfaces independent of the utilized reconstruction technique. Hence, this paper aims to introduce a new quality assessment platform for the evaluation of the 3D surface reconstruction using photogrammetric data. This quality control procedure is performed while considering the quality of input data, processing procedures, and photo-realistic 3D surface modelling. The feasibility of the proposed quality control procedure is finally verified by quality assessment of the 3D surface reconstruction using images from different photogrammetric systems.

  6. Parameterization and Analysis of 3-D Solar Radiative Transfer in Clouds: Final Report

    SciTech Connect

    Jerry Y. Harrington

    2012-09-21

    This document reports on the research that we have done over the course of our two-year project. The report also covers the research done on this project during a 1 year no-cost extension of the grant. Our work has had two main, inter-related thrusts: The first thrust was to characterize the response of stratocumulus cloud structure and dynamics to systematic changes in cloud infrared radiative cooling and solar heating using one-dimensional radiative transfer models. The second was to couple a three-dimensional (3-D) solar radiative transfer model to the Large Eddy Simulation (LES) model that we use to simulate stratocumulus. The purpose of the studies with 3-D radiative transfer was to examine the possible influences of 3-D photon transport on the structure, evolution, and radiative properties of stratocumulus. While 3-D radiative transport has been examined in static cloud environments, few studies have attempted to examine whether the 3-D nature of radiative absorption and emission influence the structure and evolution of stratocumulus. We undertook this dual approach because only a small number of LES simulations with the 3-D radiative transfer model are possible due to the high computational costs. Consequently, LES simulations with a 1-D radiative transfer solver were used in order to examine the portions of stratocumulus parameter space that may be most sensitive to perturbations in the radiative fields. The goal was then to explore these sensitive regions with LES using full 3-D radiative transfer. Our overall goal was to discover whether 3-D radiative processes alter cloud structure and evolution, and whether this may have any indirect implications for cloud radiative properties. In addition, we collaborated with Dr. Tamas Varni, providing model output fields for his attempt at parameterizing 3-D radiative effects for cloud models.

  7. Nondestructive 3D confocal laser imaging with deconvolution of seven whole stardust tracks with complementary XRF and quantitative analysis

    SciTech Connect

    Greenberg, M.; Ebel, D.S.

    2009-03-19

    We present a nondestructive 3D system for analysis of whole Stardust tracks, using a combination of Laser Confocal Scanning Microscopy and synchrotron XRF. 3D deconvolution is used for optical corrections, and results of quantitative analyses of several tracks are presented. The Stardust mission to comet Wild 2 trapped many cometary and ISM particles in aerogel, leaving behind 'tracks' of melted silica aerogel on both sides of the collector. Collected particles and their tracks range in size from submicron to millimeter scale. Interstellar dust collected on the obverse of the aerogel collector is thought to have an average track length of {approx}15 {micro}m. It has been our goal to perform a total non-destructive 3D textural and XRF chemical analysis on both types of tracks. To that end, we use a combination of Laser Confocal Scanning Microscopy (LCSM) and X Ray Florescence (XRF) spectrometry. Utilized properly, the combination of 3D optical data and chemical data provides total nondestructive characterization of full tracks, prior to flattening or other destructive analysis methods. Our LCSM techniques allow imaging at 0.075 {micro}m/pixel, without the use of oil-based lenses. A full textural analysis on track No.82 is presented here as well as analysis of 6 additional tracks contained within 3 keystones (No.128, No.129 and No.140). We present a method of removing the axial distortion inherent in LCSM images, by means of a computational 3D Deconvolution algorithm, and present some preliminary experiments with computed point spread functions. The combination of 3D LCSM data and XRF data provides invaluable information, while preserving the integrity of the samples for further analysis. It is imperative that these samples, the first extraterrestrial solids returned since the Apollo era, be fully mapped nondestructively in 3D, to preserve the maximum amount of information prior to other, destructive analysis.

  8. External fixator configurations in tibia fractures: 1D optimization and 3D analysis comparison.

    PubMed

    Roseiro, Luis M; Neto, M Augusta; Amaro, Ana; Leal, Rogerio P; Samarra, Miguel C

    2014-01-01

    The use of external fixation devices in orthopedic surgery is very common in open tibial fractures. A properly applied fixator may improve the healing process while one improperly applied might delay the healing process. The several external fixator systems used in clinical today, can be categorized into uniplanar-unilateral, uniplanar-bilateral, biplanar and multiplanar. The stability on the fracture focus and, therefore, the fracture healing process, is related with the type of external fixator configuration that is selected. The aim of this study is to discuss the principles for the successful application of unilateral-uniplanar external fixation, the assembly of its components, for the case of a transverse fractures using computational models. In this context, the fixation stiffness characteristics are evaluated using a simplified 1D finite element model for the tibia and external fixator. The beams are modeled with realistic cross-sectional geometry and material properties instead of a simplified model. The VABS (the Variational Asymptotic Beam Section analysis) methodology is used to compute the cross-sectional model for the generalized Timoshenko model, which was embedded in the finite element solver FEAP. The use of Timoshenko beam theory allows accounting for several kinds of loads, including torsion moments. Optimal design is performed with respect to the assembly of fixator components using a genetic algorithm. The optimization procedure is based on the evaluation of an objective function, which is dependent on the displacement at the fracture focus. The initial and optimal results are compared by performing a 3D analysis, for which different three-dimensional finite element models are created. The geometrical model of a tibia is created on the basis of data acquired by CAT scan, made for a healthy tibia of a 22 year old male. The 3D comparison of the 1D optimal results show a clear improvement on the objective function for the several load cases and

  9. Super Cooled Large Droplet Analysis of Several Geometries Using LEWICE3D Version 3

    NASA Technical Reports Server (NTRS)

    Bidwell, Colin S.

    2011-01-01

    Super Cooled Large Droplet (SLD) collection efficiency calculations were performed for several geometries using the LEWICE3D Version 3 software. The computations were performed using the NASA Glenn Research Center SLD splashing model which has been incorporated into the LEWICE3D Version 3 software. Comparisons to experiment were made where available. The geometries included two straight wings, a swept 64A008 wing tip, two high lift geometries, and the generic commercial transport DLR-F4 wing body configuration. In general the LEWICE3D Version 3 computations compared well with the 2D LEWICE 3.2.2 results and with experimental data where available.

  10. RESTRUCTURING RELAP5-3D FOR NEXT GENERATION NUCLEAR PLANT ANALYSIS

    SciTech Connect

    Donna Post Guillen; George L. Mesina; Joshua M. Hykes

    2006-06-01

    RELAP5-3D is used worldwide for analyzing nuclear reactors under both operational transients and postulated accident conditions. Development of the RELAP code series began in 1975 and since that time the code has been continuously improved, enhanced, verified and validated [1]. Since RELAP5-3D will continue to be the premier thermal hydraulics tool well into the future, it is necessary to modernize the code to accommodate the incorporation of additional capabilities to support the development of the next generation of nuclear reactors [2]. This paper discusses the reengineering of RELAP5-3D into structured code.

  11. Analysis of 3D-printed metal for rapid-prototyped reflective terahertz optics.

    PubMed

    Headland, Daniel; Withayachumnankul, Withawat; Webb, Michael; Ebendorff-Heidepriem, Heike; Luiten, Andre; Abbott, Derek

    2016-07-25

    We explore the potential of 3D metal printing to realize complex conductive terahertz devices. Factors impacting performance such as printing resolution, surface roughness, oxidation, and material loss are investigated via analytical, numerical, and experimental approaches. The high degree of control offered by a 3D-printed topology is exploited to realize a zone plate operating at 530 GHz. Reflection efficiency at this frequency is found to be over 90%. The high-performance of this preliminary device suggest that 3D metal printing can play a strong role in guided-wave and general beam control devices in the terahertz range. PMID:27464185

  12. Analysis of 3D-printed metal for rapid-prototyped reflective terahertz optics

    NASA Astrophysics Data System (ADS)

    Headland, Daniel; Withayachumnankul, Withawat; Webb, Michael; Ebendorff-Heidepriem, Heike; Luiten, Andre; Abbott, Derek

    2016-07-01

    We explore the potential of 3D metal printing to realize complex conductive terahertz devices. Factors impacting performance such as printing resolution, surface roughness, oxidation, and material loss are investigated via analytical, numerical, and experimental approaches. The high degree of control offered by a 3D-printed topology is exploited to realize a zone plate operating at 530 GHz. Reflection efficiency at this frequency is found to be over 90%. The high-performance of this preliminary device suggest that 3D metal printing can play a strong role in guided-wave and general beam control devices in the terahertz range.

  13. Analysis of 3D-printed metal for rapid-prototyped reflective terahertz optics.

    PubMed

    Headland, Daniel; Withayachumnankul, Withawat; Webb, Michael; Ebendorff-Heidepriem, Heike; Luiten, Andre; Abbott, Derek

    2016-07-25

    We explore the potential of 3D metal printing to realize complex conductive terahertz devices. Factors impacting performance such as printing resolution, surface roughness, oxidation, and material loss are investigated via analytical, numerical, and experimental approaches. The high degree of control offered by a 3D-printed topology is exploited to realize a zone plate operating at 530 GHz. Reflection efficiency at this frequency is found to be over 90%. The high-performance of this preliminary device suggest that 3D metal printing can play a strong role in guided-wave and general beam control devices in the terahertz range.

  14. Meshless deformable models for 3D cardiac motion and strain analysis from tagged MRI.

    PubMed

    Wang, Xiaoxu; Chen, Ting; Zhang, Shaoting; Schaerer, Joël; Qian, Zhen; Huh, Suejung; Metaxas, Dimitris; Axel, Leon

    2015-01-01

    Tagged magnetic resonance imaging (TMRI) provides a direct and noninvasive way to visualize the in-wall deformation of the myocardium. Due to the through-plane motion, the tracking of 3D trajectories of the material points and the computation of 3D strain field call for the necessity of building 3D cardiac deformable models. The intersections of three stacks of orthogonal tagging planes are material points in the myocardium. With these intersections as control points, 3D motion can be reconstructed with a novel meshless deformable model (MDM). Volumetric MDMs describe an object as point cloud inside the object boundary and the coordinate of each point can be written in parametric functions. A generic heart mesh is registered on the TMRI with polar decomposition. A 3D MDM is generated and deformed with MR image tagging lines. Volumetric MDMs are deformed by calculating the dynamics function and minimizing the local Laplacian coordinates. The similarity transformation of each point is computed by assuming its neighboring points are making the same transformation. The deformation is computed iteratively until the control points match the target positions in the consecutive image frame. The 3D strain field is computed from the 3D displacement field with moving least squares. We demonstrate that MDMs outperformed the finite element method and the spline method with a numerical phantom. Meshless deformable models can track the trajectory of any material point in the myocardium and compute the 3D strain field of any particular area. The experimental results on in vivo healthy and patient heart MRI show that the MDM can fully recover the myocardium motion in three dimensions.

  15. Meshless deformable models for 3D cardiac motion and strain analysis from tagged MRI.

    PubMed

    Wang, Xiaoxu; Chen, Ting; Zhang, Shaoting; Schaerer, Joël; Qian, Zhen; Huh, Suejung; Metaxas, Dimitris; Axel, Leon

    2015-01-01

    Tagged magnetic resonance imaging (TMRI) provides a direct and noninvasive way to visualize the in-wall deformation of the myocardium. Due to the through-plane motion, the tracking of 3D trajectories of the material points and the computation of 3D strain field call for the necessity of building 3D cardiac deformable models. The intersections of three stacks of orthogonal tagging planes are material points in the myocardium. With these intersections as control points, 3D motion can be reconstructed with a novel meshless deformable model (MDM). Volumetric MDMs describe an object as point cloud inside the object boundary and the coordinate of each point can be written in parametric functions. A generic heart mesh is registered on the TMRI with polar decomposition. A 3D MDM is generated and deformed with MR image tagging lines. Volumetric MDMs are deformed by calculating the dynamics function and minimizing the local Laplacian coordinates. The similarity transformation of each point is computed by assuming its neighboring points are making the same transformation. The deformation is computed iteratively until the control points match the target positions in the consecutive image frame. The 3D strain field is computed from the 3D displacement field with moving least squares. We demonstrate that MDMs outperformed the finite element method and the spline method with a numerical phantom. Meshless deformable models can track the trajectory of any material point in the myocardium and compute the 3D strain field of any particular area. The experimental results on in vivo healthy and patient heart MRI show that the MDM can fully recover the myocardium motion in three dimensions. PMID:25157446

  16. Meshless deformable models for 3D cardiac motion and strain analysis from tagged MRI

    PubMed Central

    Wang, Xiaoxu; Chen, Ting; Zhang, Shaoting; Schaerer, Joël; Qian, Zhen; Huh, Suejung; Metaxas, Dimitris; Axel, Leon

    2016-01-01

    Tagged magnetic resonance imaging (TMRI) provides a direct and noninvasive way to visualize the in-wall deformation of the myocardium. Due to the through-plane motion, the tracking of 3D trajectories of the material points and the computation of 3D strain field call for the necessity of building 3D cardiac deformable models. The intersections of three stacks of orthogonal tagging planes are material points in the myocardium. With these intersections as control points, 3D motion can be reconstructed with a novel meshless deformable model (MDM). Volumetric MDMs describe an object as point cloud inside the object boundary and the coordinate of each point can be written in parametric functions. A generic heart mesh is registered on the TMRI with polar decomposition. A 3D MDM is generated and deformed with MR image tagging lines. Volumetric MDMs are deformed by calculating the dynamics function and minimizing the local Laplacian coordinates. The similarity transformation of each point is computed by assuming its neighboring points are making the same transformation. The deformation is computed iteratively until the control points match the target positions in the consecutive image frame. The 3D strain field is computed from the 3D displacement field with moving least squares. We demonstrate that MDMs outperformed the finite element method and the spline method with a numerical phantom. Meshless deformable models can track the trajectory of any material point in the myocardium and compute the 3D strain field of any particular area. The experimental results on in vivo healthy and patient heart MRI show that the MDM can fully recover the myocardium motion in three dimensions. PMID:25157446

  17. Breast Density Analysis with Automated Whole-Breast Ultrasound: Comparison with 3-D Magnetic Resonance Imaging.

    PubMed

    Chen, Jeon-Hor; Lee, Yan-Wei; Chan, Si-Wa; Yeh, Dah-Cherng; Chang, Ruey-Feng

    2016-05-01

    In this study, a semi-automatic breast segmentation method was proposed on the basis of the rib shadow to extract breast regions from 3-D automated whole-breast ultrasound (ABUS) images. The density results were correlated with breast density values acquired with 3-D magnetic resonance imaging (MRI). MRI images of 46 breasts were collected from 23 women without a history of breast disease. Each subject also underwent ABUS. We used Otsu's thresholding method on ABUS images to obtain local rib shadow information, which was combined with the global rib shadow information (extracted from all slice projections) and integrated with the anatomy's breast tissue structure to determine the chest wall line. The fuzzy C-means classifier was used to extract the fibroglandular tissues from the acquired images. Whole-breast volume (WBV) and breast percentage density (BPD) were calculated in both modalities. Linear regression was used to compute the correlation of density results between the two modalities. The consistency of density measurement was also analyzed on the basis of intra- and inter-operator variation. There was a high correlation of density results between MRI and ABUS (R(2) = 0.798 for WBV, R(2) = 0.825 for PBD). The mean WBV from ABUS images was slightly smaller than the mean WBV from MR images (MRI: 342.24 ± 128.08 cm(3), ABUS: 325.47 ± 136.16 cm(3), p < 0.05). In addition, the BPD calculated from MR images was smaller than the BPD from ABUS images (MRI: 24.71 ± 15.16%, ABUS: 28.90 ± 17.73%, p < 0.05). The intra-operator and inter-operator variant analysis results indicated that there was no statistically significant difference in breast density measurement variation between the two modalities. Our results revealed a high correlation in WBV and BPD between MRI and ABUS. Our study suggests that ABUS provides breast density information useful in the assessment of breast health. PMID:26831342

  18. Breast Density Analysis with Automated Whole-Breast Ultrasound: Comparison with 3-D Magnetic Resonance Imaging.

    PubMed

    Chen, Jeon-Hor; Lee, Yan-Wei; Chan, Si-Wa; Yeh, Dah-Cherng; Chang, Ruey-Feng

    2016-05-01

    In this study, a semi-automatic breast segmentation method was proposed on the basis of the rib shadow to extract breast regions from 3-D automated whole-breast ultrasound (ABUS) images. The density results were correlated with breast density values acquired with 3-D magnetic resonance imaging (MRI). MRI images of 46 breasts were collected from 23 women without a history of breast disease. Each subject also underwent ABUS. We used Otsu's thresholding method on ABUS images to obtain local rib shadow information, which was combined with the global rib shadow information (extracted from all slice projections) and integrated with the anatomy's breast tissue structure to determine the chest wall line. The fuzzy C-means classifier was used to extract the fibroglandular tissues from the acquired images. Whole-breast volume (WBV) and breast percentage density (BPD) were calculated in both modalities. Linear regression was used to compute the correlation of density results between the two modalities. The consistency of density measurement was also analyzed on the basis of intra- and inter-operator variation. There was a high correlation of density results between MRI and ABUS (R(2) = 0.798 for WBV, R(2) = 0.825 for PBD). The mean WBV from ABUS images was slightly smaller than the mean WBV from MR images (MRI: 342.24 ± 128.08 cm(3), ABUS: 325.47 ± 136.16 cm(3), p < 0.05). In addition, the BPD calculated from MR images was smaller than the BPD from ABUS images (MRI: 24.71 ± 15.16%, ABUS: 28.90 ± 17.73%, p < 0.05). The intra-operator and inter-operator variant analysis results indicated that there was no statistically significant difference in breast density measurement variation between the two modalities. Our results revealed a high correlation in WBV and BPD between MRI and ABUS. Our study suggests that ABUS provides breast density information useful in the assessment of breast health.

  19. CCTV Coverage Index Based on Surveillance Resolution and Its Evaluation Using 3D Spatial Analysis

    PubMed Central

    Choi, Kyoungah; Lee, Impyeong

    2015-01-01

    We propose a novel approach to evaluating how effectively a closed circuit television (CCTV) system can monitor a targeted area. With 3D models of the target area and the camera parameters of the CCTV system, the approach produces surveillance coverage index, which is newly defined in this study as a quantitative measure for surveillance performance. This index indicates the proportion of the space being monitored with a sufficient resolution to the entire space of the target area. It is determined by computing surveillance resolution at every position and orientation, which indicates how closely a specific object can be monitored with a CCTV system. We present full mathematical derivation for the resolution, which depends on the location and orientation of the object as well as the geometric model of a camera. With the proposed approach, we quantitatively evaluated the surveillance coverage of a CCTV system in an underground parking area. Our evaluation process provided various quantitative-analysis results, compelling us to examine the design of the CCTV system prior to its installation and understand the surveillance capability of an existing CCTV system. PMID:26389909

  20. Electrical performance analysis of HTS synchronous motor based on 3D FEM

    NASA Astrophysics Data System (ADS)

    Baik, S. K.; Kwon, Y. K.; Kim, H. M.; Lee, J. D.; Kim, Y. C.; Park, G. S.

    2010-11-01

    A 1-MW class superconducting motor with High-Temperature Superconducting (HTS) field coil is analyzed and tested. This machine is a prototype to make sure applicability aimed at generator and industrial motor applications such as blowers, pumps and compressors installed in large plants. This machine has the HTS field coil made of Bi-2223 HTS wire and the conventional copper armature (stator) coils cooled by water. The 1-MW class HTS motor is analyzed by 3D electromagnetic Finite Element Method (FEM) to get magnetic field distribution, self and mutual inductance, and so forth. Especially excitation voltage (Back EMF) is estimated by using the mutual inductance between armature and field coils and compared with experimental result. Open and short circuit tests were conducted in generator mode while a 1.1-MW rated induction machine was rotating the HTS machine. Electrical parameters such as mutual inductance and synchronous inductance are deduced from these tests and also compared with the analysis results from FEM.

  1. Braking Distance Prediction by Hydroplaning Analysis of 3-D Patterned Tire Model

    NASA Astrophysics Data System (ADS)

    Cho, Jin-Rae; Choi, Joo-Hyoung; Lee, Hong-Woo; Woo, Jong-Shik; Yoo, Wan-Suk

    In this paper, we present a wet-road braking distance estimate for the vehicles equipped with ABS (Anti-lock Brake System). In order to effectively compute the interval-wise braking times and the resulting total braking distance, we divide the entire speed interval at braking into finite number of uniform sub-intervals and apply the energy conservation law to individual sub-intervals. The proposed method is based on a numerical-analytical approach such that the frictional energy loss of the patterned tire is computed by 3-D hydroplaning analysis while the other at the disc pad is analytically derived. The hydroplaning simulation is performed by generally coupling an Eulerian finite volume method and an explicit Lagrangian finite element method. The operation of ABS is numerically implemented by controlling the tire angular velocity such that the preset tire slip ratio on the wet road is maintained. Numerical results are presented to illustrative and verify the the proposed numerical estimate.

  2. Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

    PubMed Central

    Li, Wenyuan; Kalhor, Reza; Dai, Chao; Hao, Shengli; Gong, Ke; Zhou, Yonggang; Li, Haochen; Zhou, Xianghong Jasmine; Le Gros, Mark A.; Larabell, Carolyn A.; Chen, Lin; Alber, Frank

    2016-01-01

    Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization. PMID:26951677

  3. CraMs: Craniometric Analysis Application Using 3D Skull Models.

    PubMed

    Dias, Paulo; Neves, Luis; Santos, Daniel; Coelho, Catarina; Ferreira, Maria Teresa; Santos, Helder; Silva, Samuel; Santos, Beatriz Sousa

    2015-01-01

    Craniometric analysis plays an important role in anthropology studies and forensics. This paper presents CraMs, an application using a new craniometric approach based on 3D models of the skull. The main objective is to obtain, through a process supervised by anthropologists, the main points of interest used to compute craniometric measurements. The application aids this process by analyzing the skull geometry and automatically providing points of interest. The application also allows for semiautomatic point detection, where the user provides an initial guess that might be refined based on the curvature of the skull, as well as the manual selection of any other points of interest. Moreover, results comparing measurements obtained with CraMs and traditional craniometry methods on eight skulls suggest that the application provides comparable craniometric measurements and lower inter-observer variability. This approach offers advantages such as an easier access to skulls with no risk of bone damage and the possibility of defining new measurements based on morphology or other skull characteristics, which are not possible using traditional methods. PMID:26594956

  4. Cluster Analysis and Web-Based 3-D Visualization of Large-scale Geophysical Data

    NASA Astrophysics Data System (ADS)

    Kadlec, B. J.; Yuen, D. A.; Bollig, E. F.; Dzwinel, W.; da Silva, C. R.

    2004-05-01

    We present a problem-solving environment WEB-IS (Web-based Data Interrogative System), which we have developed for remote analysis and visualization of geophysical data [Garbow et. al., 2003]. WEB-IS employs agglomerative clustering methods intended for feature extraction and studying the predictions of large magnitude earthquake events. Data-mining is accomplished using a mutual nearest meighbor (MNN) algorithm for extracting event clusters of different density and shapes based on a hierarchical proximity measure. Clustering schemes used in molecular dynamics [Da Silva et. al., 2002] are also considered for increasing computational efficiency using a linked cell algorithm for creating a Verlet neighbor list (VNL) and extracting different cluster structures by applying a canonical backtracking search on the VNL. Space and time correlations between the events are visualized dynamically in 3-D through a filter by showing clusters at different timescales according to defined units of time ranging from days to years. This WEB-IS functionality was tested both on synthetic [Eneva and Ben-Zion, 1997] and actual earthquake catalogs of Japanese earthquakes and can be applied to the soft-computing data mining methods used in hydrology and geoinformatics. Da Silva, C.R.S., Justo, J.F., Fazzio, A., Phys Rev B, vol., 65, 2002. Eneva, M., Ben-Zion, Y.,J. Geophys. Res., 102, 17785-17795, 1997. Garbow, Z.A., Yuen, D.A., Erlebacher, G., Bollig, E.F., Kadlec, B.J., Vis. Geosci., 2003.

  5. Analysis and modeling of 3D complex modulus tests on hot and warm bituminous mixtures

    NASA Astrophysics Data System (ADS)

    Pham, Nguyen Hoang; Sauzéat, Cédric; Di Benedetto, Hervé; González-León, Juan A.; Barreto, Gilles; Nicolaï, Aurélia; Jakubowski, Marc

    2015-05-01

    This paper presents the results of laboratory testing of hot and warm bituminous mixtures containing Reclaimed Asphalt Pavement (RAP). Complex modulus measurements, using the tension-compression test on cylindrical specimens, were conducted to determine linear viscoelastic (LVE) behavior. Sinusoidal cyclic loadings, with strain amplitude of approximately 50ṡ10-6, were applied at several temperatures (from -25 to +45 °C) and frequencies (from 0.03 Hz to 10 Hz). In addition to axial stresses and strains, radial strains were also measured. The complex modulus E ∗ and complex Poisson's ratios ν ∗ were then obtained in two perpendicular directions. Measured values in these two directions do not indicate anisotropy on Poisson's ratio. The time-temperature superposition principle (TTSP) was verified with good approximation in one-dimensional (1D) and three-dimensional (3D) conditions for the same values of shift factor. Experimental results were modeled using the 2S2P1D model previously developed at the University of Lyon/ENTPE. In addition, specific analysis showed that eventual damage created during complex modulus test is very small and is equivalent to the effect of an increase of temperature of about 0.25 °C.

  6. Fibrillogenesis from nanosurfaces: multiphoton imaging and stereological analysis of collagen 3D self-assembly dynamics.

    PubMed

    Bancelin, Stéphane; Decencière, Etienne; Machairas, Vaïa; Albert, Claire; Coradin, Thibaud; Schanne-Klein, Marie-Claire; Aimé, Carole

    2014-09-21

    The assembly of proteins into fibrillar structures is an important process that concerns different biological contexts, including molecular medicine and functional biomaterials. Engineering of hybrid biomaterials can advantageously provide synergetic interactions of the biopolymers with an inorganic component to ensure specific supramolecular organization and dynamics. To this aim, we designed hybrid systems associating collagen and surface-functionalized silica particles and we built a new strategy to investigate fibrillogenesis processes in such multicomponents systems, working at the crossroads of chemistry, physics and mathematics. The self-assembly process was investigated by bimodal multiphoton imaging coupling second harmonic generation (SHG) and 2 photon excited fluorescence (2PEF). The in-depth spatial characterization of the system was further achieved using the three-dimensional analysis of the SHG/2PEF data via mathematical morphology processing. Quantitation of collagen distribution around particles offers strong evidence that the chemically induced confinement of the protein on the silica nanosurfaces has a key influence on the spatial extension of fibrillogenesis. This new approach is unique in the information it can provide on 3D dynamic hybrid systems and may be extended to other associations of fibrillar molecules with optically responsive nano-objects. PMID:25058449

  7. Filtered chorochronic interface as a capability for 3-D unsteady throughflow analysis of multistage turbomachinery

    NASA Astrophysics Data System (ADS)

    Gerolymos, G. A.

    2013-02-01

    This note reviews the widely used phased-lagged [Erdos, J. L., E. Alzner, and W. McNally. 1977. AIAA Journal 15: 1559-68.] approach and corresponding chorochronic interface relations [Gerolymos G. A., G. J. Michon, and J. Neubauer. 2002. Journal of Propulsion and Power 18: 1139-52.] and explores its potential extension to the approximate unsteady throughflow analysis of multistage turbomachinery. The basic relations pertaining to the binary blade-row interaction case, for which chorochronic periodicity is exact in a phase-averaged rans framework, are briefly formulated, and selected computational examples illustrate the application of the method. Then, the filtered chorochronic interface is defined as the unsteady counterpart of the well-known mixing-plane concept. This interface takes into account only those tθ-waves which are compatible with the interaction of the immediately upstream and downstream blade-rows. The concept, which is similar to the decomposition-and-superposition method [Li, H. D., and L. He. 2005. ASME J ournal of Turbomachinery 127: 589-98.], is illustrated by 3-D computations of a ½-stage transonic compressor.

  8. Assessment of a nanocrystal 3-D morphology by the analysis of single HAADF-HRSTEM images

    PubMed Central

    2013-01-01

    This work presents the morphological characterization of CeO2 nanocrystals by the analysis of single unfiltered high-angle annular dark-field (HAADF)-high-resolution scanning transmission electron microscopy (HRSTEM) images. The thickness of each individual atomic column is estimated by the classification of its HAADF integrated intensity using a Gaussian mixture model. The resulting thickness maps obtained from two example nanocrystals with distinct morphology were analyzed with aid of the symmetry from the CeO2 crystallographic structure, providing an approximation for their 3-D morphology with high spatial resolution. A confidence level of ±1 atom per atomic column along the viewing direction on the thickness estimation is indicated by the use of multislice image simulation. The described characterization procedure stands out as a simple approach for retrieving morphological parameters of individual nanocrystals, such as volume and specific surface areas for different crystalline planes. The procedure is an alternative to the tilt-series tomography technique for a number of nanocrystalline systems, since its application does not require the acquisition of multiple images from the same nanocrystal along different zone axes. PMID:24225330

  9. CraMs: Craniometric Analysis Application Using 3D Skull Models.

    PubMed

    Dias, Paulo; Neves, Luis; Santos, Daniel; Coelho, Catarina; Ferreira, Maria Teresa; Santos, Helder; Silva, Samuel; Santos, Beatriz Sousa

    2015-01-01

    Craniometric analysis plays an important role in anthropology studies and forensics. This paper presents CraMs, an application using a new craniometric approach based on 3D models of the skull. The main objective is to obtain, through a process supervised by anthropologists, the main points of interest used to compute craniometric measurements. The application aids this process by analyzing the skull geometry and automatically providing points of interest. The application also allows for semiautomatic point detection, where the user provides an initial guess that might be refined based on the curvature of the skull, as well as the manual selection of any other points of interest. Moreover, results comparing measurements obtained with CraMs and traditional craniometry methods on eight skulls suggest that the application provides comparable craniometric measurements and lower inter-observer variability. This approach offers advantages such as an easier access to skulls with no risk of bone damage and the possibility of defining new measurements based on morphology or other skull characteristics, which are not possible using traditional methods.

  10. Understanding North Texas Seismicity: A Joint Analysis of Seismic Data and 3D Pore Pressure Modeling

    NASA Astrophysics Data System (ADS)

    DeShon, H. R.; Hornbach, M. J.; Ellsworth, W. L.; Oldham, H. R.; Hayward, C.; Stump, B. W.; Frohlich, C.; Olson, J. E.; Luetgert, J. H.

    2014-12-01

    In November 2013, a series of earthquakes began along a mapped ancient fault system near Azle, Texas. The Azle events are the third felt earthquake sequence in the Fort Worth (Barnett Shale) Basin since 2008, and several production and injection wells in the area are drilled to depths near the recent seismic activity. Understanding if and/or how injection and removal of fluids in the crystalline crust reactivates faults have important implications for seismology, the energy industry, and society. We assessed whether the Azle earthquakes were induced using a joint analysis of the earthquake data, subsurface geology and fault structure, and 3D pore pressure modeling. Using a 12-station temporary seismic deployment, we have recorded and located >300 events large enough to be recorded on multiple stations and 1000s of events during periods of swarm activity. High-resolution locations and focal mechanisms indicate that events occurred on NE-SW trending, steeply dipping normal faults associated with the southern end of the Newark East Fault Zone with hypocenters between 2-8 km depth. We considered multiple causes that might have changed stress along this system. Earthquakes resulting from natural processes, though perhaps unlikely in this historically inactive region, can be neither ruled out nor confirmed due to lack of information on the natural stress state of these faults. Analysis of lake and groundwater variations near Azle showed that no significant stress changes occurred prior to or during the earthquake sequence. In contrast, analysis of pore-pressure models shows that the combination of formation water production and wastewater injection near the fault could have caused pressure increases that induced earthquakes on near-critically stressed faults.

  11. A Workstation for Interactive Display and Quantitative Analysis of 3-D and 4-D Biomedical Images

    PubMed Central

    Robb, R.A.; Heffeman, P.B.; Camp, J.J.; Hanson, D.P.

    1986-01-01

    The capability to extract objective and quantitatively accurate information from 3-D radiographic biomedical images has not kept pace with the capabilities to produce the images themselves. This is rather an ironic paradox, since on the one hand the new 3-D and 4-D imaging capabilities promise significant potential for providing greater specificity and sensitivity (i.e., precise objective discrimination and accurate quantitative measurement of body tissue characteristics and function) in clinical diagnostic and basic investigative imaging procedures than ever possible before, but on the other hand, the momentous advances in computer and associated electronic imaging technology which have made these 3-D imaging capabilities possible have not been concomitantly developed for full exploitation of these capabilities. Therefore, we have developed a powerful new microcomputer-based system which permits detailed investigations and evaluation of 3-D and 4-D (dynamic 3-D) biomedical images. The system comprises a special workstation to which all the information in a large 3-D image data base is accessible for rapid display, manipulation, and measurement. The system provides important capabilities for simultaneously representing and analyzing both structural and functional data and their relationships in various organs of the body. This paper provides a detailed description of this system, as well as some of the rationale, background, theoretical concepts, and practical considerations related to system implementation. ImagesFigure 5Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16

  12. Analysis and Visualization of 3D Motion Data for UPDRS Rating of Patients with Parkinson's Disease.

    PubMed

    Piro, Neltje E; Piro, Lennart K; Kassubek, Jan; Blechschmidt-Trapp, Ronald A

    2016-01-01

    Remote monitoring of Parkinson's Disease (PD) patients with inertia sensors is a relevant method for a better assessment of symptoms. We present a new approach for symptom quantification based on motion data: the automatic Unified Parkinson Disease Rating Scale (UPDRS) classification in combination with an animated 3D avatar giving the neurologist the impression of having the patient live in front of him. In this study we compared the UPDRS ratings of the pronation-supination task derived from: (a) an examination based on video recordings as a clinical reference; (b) an automatically classified UPDRS; and (c) a UPDRS rating from the assessment of the animated 3D avatar. Data were recorded using Magnetic, Angular Rate, Gravity (MARG) sensors with 15 subjects performing a pronation-supination movement of the hand. After preprocessing, the data were classified with a J48 classifier and animated as a 3D avatar. Video recording of the movements, as well as the 3D avatar, were examined by movement disorder specialists and rated by UPDRS. The mean agreement between the ratings based on video and (b) the automatically classified UPDRS is 0.48 and with (c) the 3D avatar it is 0.47. The 3D avatar is similarly suitable for assessing the UPDRS as video recordings for the examined task and will be further developed by the research team. PMID:27338400

  13. A Shell/3D Modeling Technique for the Analysis of Delaminated Composite Laminates

    NASA Technical Reports Server (NTRS)

    Krueger, Ronald; OBrien, T. Kevin

    2000-01-01

    A shell/3D modeling technique was developed for which a local solid finite element model is used only in the immediate vicinity of the delamination front. The goal was to combine the accuracy of the full three-dimensional solution with the computational efficiency of a shell finite element model. Multi-point constraints provided a kinematically compatible interface between the local 3D model and the global structural model which has been meshed with shell finite elements. Double Cantilever Beam, End Notched Flexure, and Single Leg Bending specimens were analyzed first using full 3D finite element models to obtain reference solutions. Mixed mode strain energy release rate distributions were computed using the virtual crack closure technique. The analyses were repeated using the shell/3D technique to study the feasibility for pure mode I, mode II and mixed mode I/II cases. Specimens with a unidirectional layup and with a multidirectional layup were simulated. For a local 3D model, extending to a minimum of about three specimen thicknesses on either side of the delamination front, the results were in good agreement with mixed mode strain energy release rates obtained from computations where the entire specimen had been modeled with solid elements. For large built-up composite structures the shell/3D modeling technique offers a great potential for reducing the model size, since only a relatively small section in the vicinity of the delamination front needs to be modeled with solid elements.

  14. Performance Analysis of a Low-Cost Triangulation-Based 3d Camera: Microsoft Kinect System

    NASA Astrophysics Data System (ADS)

    . K. Chow, J. C.; Ang, K. D.; Lichti, D. D.; Teskey, W. F.

    2012-07-01

    Recent technological advancements have made active imaging sensors popular for 3D modelling and motion tracking. The 3D coordinates of signalised targets are traditionally estimated by matching conjugate points in overlapping images. Current 3D cameras can acquire point clouds at video frame rates from a single exposure station. In the area of 3D cameras, Microsoft and PrimeSense have collaborated and developed an active 3D camera based on the triangulation principle, known as the Kinect system. This off-the-shelf system costs less than 150 USD and has drawn a lot of attention from the robotics, computer vision, and photogrammetry disciplines. In this paper, the prospect of using the Kinect system for precise engineering applications was evaluated. The geometric quality of the Kinect system as a function of the scene (i.e. variation of depth, ambient light conditions, incidence angle, and object reflectivity) and the sensor (i.e. warm-up time and distance averaging) were analysed quantitatively. This system's potential in human body measurements was tested against a laser scanner and 3D range camera. A new calibration model for simultaneously determining the exterior orientation parameters, interior orientation parameters, boresight angles, leverarm, and object space features parameters was developed and the effectiveness of this calibration approach was explored.

  15. A study of electrochemical biosensor for analysis of three-dimensional (3D) cell culture.

    PubMed

    Jeong, Se Hoon; Lee, Dong Woo; Kim, Sanghyo; Kim, Jhingook; Ku, Bosung

    2012-05-15

    Cell culture has a fundamental role not only in regenerative medicine but also in biotechnology, pharmacology, impacting both drug discovery and manufacturing. Although cell culture has been generally developed for only two-dimensional (2D) culture systems, three-dimensional (3D) culture is being spotlighted as the means to mimic in vivo cellular conditions. In this study, a method for cytotoxicity assay using an electrochemical biosensor applying 3D cell culture is presented. In order to strengthen the advantage of a 3D cell culture, the experimental condition of gelation between several types of sol-gels (alginate, collagen, matrigel) and cancer cells can be optimized to make a 3D cell structure on the electrode, which will show the reproducibility of electrical measurement for long-term monitoring. Moreover, cytotoxicity test results applying this method showed IC(50) value of A549 lung cancer cells to erlotinib. Thus, this study evaluates the feasibility of application of the electrochemical biosensor for 3D cell culture to cytotoxicity assay for investigation of 3D cell response to drug compounds. PMID:22410483

  16. 3-D segmentation and quantitative analysis of inner and outer walls of thrombotic abdominal aortic aneurysms

    NASA Astrophysics Data System (ADS)

    Lee, Kyungmoo; Yin, Yin; Wahle, Andreas; Olszewski, Mark E.; Sonka, Milan

    2008-03-01

    An abdominal aortic aneurysm (AAA) is an area of a localized widening of the abdominal aorta, with a frequent presence of thrombus. A ruptured aneurysm can cause death due to severe internal bleeding. AAA thrombus segmentation and quantitative analysis are of paramount importance for diagnosis, risk assessment, and determination of treatment options. Until now, only a small number of methods for thrombus segmentation and analysis have been presented in the literature, either requiring substantial user interaction or exhibiting insufficient performance. We report a novel method offering minimal user interaction and high accuracy. Our thrombus segmentation method is composed of an initial automated luminal surface segmentation, followed by a cost function-based optimal segmentation of the inner and outer surfaces of the aortic wall. The approach utilizes the power and flexibility of the optimal triangle mesh-based 3-D graph search method, in which cost functions for thrombus inner and outer surfaces are based on gradient magnitudes. Sometimes local failures caused by image ambiguity occur, in which case several control points are used to guide the computer segmentation without the need to trace borders manually. Our method was tested in 9 MDCT image datasets (951 image slices). With the exception of a case in which the thrombus was highly eccentric, visually acceptable aortic lumen and thrombus segmentation results were achieved. No user interaction was used in 3 out of 8 datasets, and 7.80 +/- 2.71 mouse clicks per case / 0.083 +/- 0.035 mouse clicks per image slice were required in the remaining 5 datasets.

  17. 3D micro profile measurement with the method of spatial frequency domain analysis

    NASA Astrophysics Data System (ADS)

    Xu, Yongxiang

    2015-10-01

    3D micro profiles are often needed for measurement in many fields, e.g., binary optics, electronic industry, mechanical manufacturing, aeronautic and space industry, etc. In the case where height difference between two neighboring points of a test profile is equal to or greater than λ / 4, microscopic interferometry based on laser source will no longer be applicable because of the uncertainty in phase unwrapping. As white light possesses the characteristic of interference length approximate to zero, applying it for micro profilometry can avoid the trouble and can yield accurate results. Using self-developed Mirau-type scanning interference microscope, a step-like sample was tested twice, with 128 scanning interferograms recorded for each test. To process each set of the interferograms, the method of spatial frequency domain analysis was adopted. That is, for each point, by use of Furrier transform, white-light interference intensities were decomposed in spatial frequency domain, thus obtaining phase values corresponding to different wavenumbers; by using least square fitting on phases and wave numbers, a group-velocity OPD was gained for the very point; and finally in terms of the relation between relative height and the group-velocity OPD, the profile of the test sample was obtained. Two tests yielded same profile result for the sample, and step heights obtained were 50.88 nm and 50.94 nm, respectively. Meantime, the sample was also measured with a Zygo Newview 7200 topography instrument, with same profile result obtained and step height differing by 0.9 nm. In addition, data processing results indicate that chromatic dispersion equal to and higher than 2nd order is negligible when applying spatial frequency domain analysis method.

  18. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d.

    PubMed

    Hannan, Jonathan P; Young, Kendra A; Guthridge, Joel M; Asokan, Rengasamy; Szakonyi, Gerda; Chen, Xiaojiang S; Holers, V Michael

    2005-02-25

    We have characterized the interaction between the first two short consensus repeats (SCR1-2) of complement receptor type 2 (CR2, CD21) and C3d in solution, by utilising the available crystal structures of free and C3d-bound forms of CR2 to create a series of informative mutations targeting specific areas of the CR2-C3d complex. Wild-type and mutant forms of CR2 were expressed on the surface of K562 erythroleukemia cells and their binding ability assessed using C3dg-biotin tetramers complexed to fluorochrome conjugated streptavidin and measured by flow cytometry. Mutations directed at the SCR2-C3d interface (R83A, R83E, G84Y) were found to strongly disrupt C3dg binding, supporting the conclusion that the SCR2 interface reflected in the crystal structure is correct. Previous epitope and peptide mapping studies have also indicated that the PILN11GR13IS sequence of the first inter-cysteine region of SCR1 is essential for the binding of iC3b. Mutations targeting residues within or in close spatial proximity to this area (N11A, N11E, R13A, R13E, Y16A, S32A, S32E), and a number of other positively charged residues located primarily on a contiguous face of SCR1 (R28A, R28E, R36A, R36E, K41A, K41E, K50A, K50E, K57A, K57E, K67A, K67E), have allowed us to reassess those regions on SCR1 that are essential for CR2-C3d binding. The nature of this interaction and the possibility of a direct SCR1-C3d association are discussed extensively. Finally, a D52N mutant was constructed introducing an N-glycosylation sequence at an area central to the CR2 dimer interface. This mutation was designed to disrupt the CR2-C3d interaction, either directly through steric inhibition, or indirectly through disruption of a physiological dimer. However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2.

  19. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d.

    PubMed

    Hannan, Jonathan P; Young, Kendra A; Guthridge, Joel M; Asokan, Rengasamy; Szakonyi, Gerda; Chen, Xiaojiang S; Holers, V Michael

    2005-02-25

    We have characterized the interaction between the first two short consensus repeats (SCR1-2) of complement receptor type 2 (CR2, CD21) and C3d in solution, by utilising the available crystal structures of free and C3d-bound forms of CR2 to create a series of informative mutations targeting specific areas of the CR2-C3d complex. Wild-type and mutant forms of CR2 were expressed on the surface of K562 erythroleukemia cells and their binding ability assessed using C3dg-biotin tetramers complexed to fluorochrome conjugated streptavidin and measured by flow cytometry. Mutations directed at the SCR2-C3d interface (R83A, R83E, G84Y) were found to strongly disrupt C3dg binding, supporting the conclusion that the SCR2 interface reflected in the crystal structure is correct. Previous epitope and peptide mapping studies have also indicated that the PILN11GR13IS sequence of the first inter-cysteine region of SCR1 is essential for the binding of iC3b. Mutations targeting residues within or in close spatial proximity to this area (N11A, N11E, R13A, R13E, Y16A, S32A, S32E), and a number of other positively charged residues located primarily on a contiguous face of SCR1 (R28A, R28E, R36A, R36E, K41A, K41E, K50A, K50E, K57A, K57E, K67A, K67E), have allowed us to reassess those regions on SCR1 that are essential for CR2-C3d binding. The nature of this interaction and the possibility of a direct SCR1-C3d association are discussed extensively. Finally, a D52N mutant was constructed introducing an N-glycosylation sequence at an area central to the CR2 dimer interface. This mutation was designed to disrupt the CR2-C3d interaction, either directly through steric inhibition, or indirectly through disruption of a physiological dimer. However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2. PMID:15713467

  20. An analysis of postoperative complications and efficacy of 3-D miniplates in fixation of mandibular fractures

    PubMed Central

    Gokkulakrishnan, Sadhasivam; Singh, Sanjay; Sharma, Ashish; Shahi, Ashish Kumar

    2012-01-01

    Background: Recently, various modifications in transorally placed miniplates for direct fixation of the mandibular fracture are gaining popularity. The modifications have various advantages like more rigidity, less foreign material, less time in application, etc. Among the various modifications of miniplates, three-dimensional (3-D) plating system is also gaining popularity. Thus, in the present study, we tried to evaluate the efficacy and postoperative complications of 3-D titanium miniplates in the treatment of mandibular fractures. Materials and Methods: A prospective study was conducted on 40 patients with non-comminuted mandibular fractures. They were treated using a 2-mm 3-D titanium miniplate through intraoral approach. All patients were systematically monitored 6 months postoperatively. Outcome parameters like infection, hardware failure, wound dehiscence, sensory disturbance of the inferior alveolar nerve, occlusion, and 3-D plate stability were recorded. The statistical tests used in study were mean, standard deviation, and Chi-square test. P values less than 0.05 were considered significant and values less than 0.001 were considered very highly significant. Results: Two patients had a postoperative infection with no consequences. All patients had normal sensory function 3 months after surgery. Plate fracture had not occurred in any patient. Occlusal was normal and wound dehiscence was not reported. 3-D plate was stable in all the patients. Conclusions: It was seen that 3-D titanium miniplates were effective in the treatment of mandibular fractures and overall complication rates were lesser. In symphysis and parasymphysis regions, 3-D plating system uses lesser foreign material than the conventional miniplates using Champy's principle. PMID:23162581

  1. A comparative analysis of 2D and 3D CAD for calcifications in digital breast tomosynthesis

    NASA Astrophysics Data System (ADS)

    Acciavatti, Raymond J.; Ray, Shonket; Keller, Brad M.; Maidment, Andrew D. A.; Conant, Emily F.

    2015-03-01

    Many medical centers offer digital breast tomosynthesis (DBT) and 2D digital mammography acquired under the same compression (i.e., "Combo" examination) for screening. This paper compares a conventional 2D CAD algorithm (Hologic® ImageChecker® CAD v9.4) for calcification detection against a prototype 3D algorithm (Hologic® ImageChecker® 3D Calc CAD v1.0). Due to the newness of DBT, the development of this 3D CAD algorithm is ongoing, and it is currently not FDA-approved in the United States. For this study, DBT screening cases with suspicious calcifications were identified retrospectively at the University of Pennsylvania. An expert radiologist (E.F.C.) reviewed images with both 2D and DBT CAD marks, and compared the marks to biopsy results. Control cases with one-year negative follow-up were also studied; these cases either possess clearly benign calcifications or lacked calcifications. To allow the user to alter the sensitivity for cancer detection, an operating point is assigned to each CAD mark. As expected from conventional 2D CAD, increasing the operating point in 3D CAD increases sensitivity and reduces specificity. Additionally, we showed that some cancers are occult to 2D CAD at all operating points. By contrast, 3D CAD allows for detection of some cancers that are missed on 2D CAD. We also demonstrated that some non-cancerous CAD marks in 3D are not present at analogous locations in the 2D image. Hence, there are additional marks when using both 2D and 3D CAD in combination, leading to lower specificity than with conventional 2D CAD alone.

  2. Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

    PubMed Central

    Ling, Ted C.; Slater, Jerry M.; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M.; Patyal, Baldev; Slater, Jerry D.; Yang, Gary Y.

    2014-01-01

    Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients. PMID:25489937

  3. Mixed-Mode Fracture and Fatigue Analysis of Cracked 3D Complex Structures using a 3D SGBEM-FEM Alternating Method

    NASA Astrophysics Data System (ADS)

    Bhavanam, Sharada

    The aim of this thesis is to numerically evaluate the mixed-mode Stress Intensity Factors (SIFs) of complex 3D structural geometries with arbitrary 3D cracks using the Symmetric Galerkin Boundary Element Method-Finite Element Method (SGBEM-FEM) Alternating Method. Various structural geometries with different loading scenarios and crack configurations were examined in this thesis to understand the behavior and trends of the mixed-mode SIFs as well as the fatigue life for these complex structural geometries. Although some 3D structures have empirical and numerical solutions that are readily available in the open literature, some do not; therefore this thesis presents the results of fracture and fatigue analyses of these 3D complex structures using the SGBEM-FEM Alternating Method to serve as reference for future studies. Furthermore, there are advantages of using the SGBEM-FEM Alternating Method compared to traditional FEM methods. For example, the fatigue-crack-growth and fatigue life can be better estimated for a structure because different fatigue models (i.e. Walker, Paris, and NASGRO) can be used within the same framework of the SGBEM-FEM Alternating Method. The FEM (un-cracked structure)/BEM(crack model) meshes are modeled independently, which speeds up the computation process and reduces the cost of human labor. A simple coarse mesh can be used for all fracture and fatigue analyses of complex structures. In this thesis, simple coarse meshes were used for 3D complex structures, which were below 5000 elements as compared to traditional FEM, which require meshes where the elements range on the order of ˜250,000 to ˜106 and sometimes even more than that.

  4. Finite Element Analysis of Thermo-Mechanical Properties of 3D Braided Composites

    NASA Astrophysics Data System (ADS)

    Jiang, Li-li; Xu, Guo-dong; Cheng, Su; Lu, Xia-mei; Zeng, Tao

    2014-04-01

    This paper presents a modified finite element model (FEM) to investigate the thermo-mechanical properties of three-dimensional (3D) braided composite. The effective coefficients of thermal expansion (CTE) and the meso-scale mechanical response of 3D braided composites are predicted. The effects of the braiding angle and fiber volume fraction on the effective CTE are evaluated. The results are compared to the experimental data available in the literature to demonstrate the accuracy and reliability of the present method. The tensile stress distributions of the representative volume element (RVE) are also outlined. It is found that the stress of the braiding yarn has a significant increase with temperature rise; on the other hand, the temperature change has an insignificant effect on the stress of the matrix. In addition, a rapid decrease in the tensile strength of 3D braided composites is observed with the increase in temperature. It is revealed that the thermal conditions have a significant effect on the strength of 3D braided composites. The present method provides an effective tool to predict the stresses of 3D braided composites under thermo-mechanical loading.

  5. 3D numerical analysis of crack propagation of heterogeneous notched rock under uniaxial tension

    NASA Astrophysics Data System (ADS)

    Wang, S. Y.; Sloan, S. W.; Sheng, D. C.; Tang, C. A.

    2016-05-01

    Macroscopic notches play an important role in evaluating the fracture process zone (FPZ) and the strengths of a heterogeneous rock mass. Crack initiation, propagation and coalescence for unnotched, single-notched and double-notched rock specimens are numerically simulated in a 3-D numerical model (RFPA3D). A feature of the code RFPA3D is that it can numerically simulate the evolution of cracks in three-dimensional space, as well as the heterogeneity of the rock mass. For the unnotched case, special attention is given to the complete stress-strain curve and the corresponding AE events for the failure process of rock specimen. By comparing with published experimental results, the simulation results from RFPA3D are found to be satisfactory. For the single-notched case, the effect of the length and the depth of the single notch and the thickness of the specimen on the failure mode and peak stress are evaluated. The 3D FPZ is very different from that in two dimensions. For the double-notched case, the effects of the separation distance and overlap distance of the double notches, as well as influence of the homogeneity index (m) are also investigated. As the overlap distance increases, the direction of the principal tensile stress at each notch-end changes from a perpendicular direction (tensile stress field) to a nearly parallel direction (compressive stress field), which affects the evolution of the cracks from the two notches.

  6. Uncovering the true nature of deformation microstructures using 3D analysis methods

    NASA Astrophysics Data System (ADS)

    Ferry, M.; Quadir, M. Z.; Afrin, N.; Xu, W.; Loeb, A.; Soe, B.; McMahon, C.; George, C.; Bassman, L.

    2015-08-01

    Three-dimensional electron backscatter diffraction (3D EBSD) has emerged as a powerful technique for generating 3D crystallographic information in reasonably large volumes of a microstructure. The technique uses a focused ion beam (FIB) as a high precision serial sectioning device for generating consecutive ion milled surfaces of a material, with each milled surface subsequently mapped by EBSD. The successive EBSD maps are combined using a suitable post-processing method to generate a crystallographic volume of the microstructure. The first part of this paper shows the usefulness of 3D EBSD for understanding the origin of various structural features associated with the plastic deformation of metals. The second part describes a new method for automatically identifying the various types of low and high angle boundaries found in deformed and annealed metals, particularly those associated with grains exhibiting subtle and gradual variations in orientation. We have adapted a 2D image segmentation technique, fast multiscale clustering, to 3D EBSD data using a novel variance function to accommodate quaternion data. This adaptation is capable of segmenting based on subtle and gradual variation as well as on sharp boundaries within the data. We demonstrate the excellent capabilities of this technique with application to 3D EBSD data sets generated from a range of cold rolled and annealed metals described in the paper.

  7. Real-Time Analysis of Endogenous Wnt Signalling in 3D Mesenchymal Stromal Cells.

    PubMed

    Saleh, Fatima; Carstairs, Alice; Etheridge, S Leah; Genever, Paul

    2016-01-01

    Wnt signalling has been implicated in the regulation of stem cell self-renewal and differentiation; however, the majority of in vitro studies are carried out using monolayer 2D culture techniques. Here, we used mesenchymal stromal cell (MSC) EGFP reporter lines responsive to Wnt pathway activation in a 3D spheroid culture system to mimic better the in vivo environment. Endogenous Wnt signalling was then investigated under basal conditions and when MSCs were induced to undergo osteogenic and adipogenic differentiation. Interestingly, endogenous Wnt signalling was only active during 3D differentiation whereas 2D cultures showed no EGFP expression throughout an extended differentiation time-course. Furthermore, exogenous Wnt signalling in 3D adipogenic conditions inhibited differentiation compared to unstimulated controls. In addition, suppressing Wnt signalling by Dkk-1 restored and facilitated adipogenic differentiation in MSC spheroids. Our findings indicate that endogenous Wnt signalling is active and can be tracked in 3D MSC cultures where it may act as a molecular switch in adipogenesis. The identification of the signalling pathways that regulate MSCs in a 3D in vivo-like environment will advance our understanding of the molecular mechanisms that control MSC fate. PMID:27668000

  8. Real-Time Analysis of Endogenous Wnt Signalling in 3D Mesenchymal Stromal Cells

    PubMed Central

    Saleh, Fatima; Etheridge, S. Leah

    2016-01-01

    Wnt signalling has been implicated in the regulation of stem cell self-renewal and differentiation; however, the majority of in vitro studies are carried out using monolayer 2D culture techniques. Here, we used mesenchymal stromal cell (MSC) EGFP reporter lines responsive to Wnt pathway activation in a 3D spheroid culture system to mimic better the in vivo environment. Endogenous Wnt signalling was then investigated under basal conditions and when MSCs were induced to undergo osteogenic and adipogenic differentiation. Interestingly, endogenous Wnt signalling was only active during 3D differentiation whereas 2D cultures showed no EGFP expression throughout an extended differentiation time-course. Furthermore, exogenous Wnt signalling in 3D adipogenic conditions inhibited differentiation compared to unstimulated controls. In addition, suppressing Wnt signalling by Dkk-1 restored and facilitated adipogenic differentiation in MSC spheroids. Our findings indicate that endogenous Wnt signalling is active and can be tracked in 3D MSC cultures where it may act as a molecular switch in adipogenesis. The identification of the signalling pathways that regulate MSCs in a 3D in vivo-like environment will advance our understanding of the molecular mechanisms that control MSC fate. PMID:27668000

  9. Real-Time Analysis of Endogenous Wnt Signalling in 3D Mesenchymal Stromal Cells

    PubMed Central

    Saleh, Fatima; Etheridge, S. Leah

    2016-01-01

    Wnt signalling has been implicated in the regulation of stem cell self-renewal and differentiation; however, the majority of in vitro studies are carried out using monolayer 2D culture techniques. Here, we used mesenchymal stromal cell (MSC) EGFP reporter lines responsive to Wnt pathway activation in a 3D spheroid culture system to mimic better the in vivo environment. Endogenous Wnt signalling was then investigated under basal conditions and when MSCs were induced to undergo osteogenic and adipogenic differentiation. Interestingly, endogenous Wnt signalling was only active during 3D differentiation whereas 2D cultures showed no EGFP expression throughout an extended differentiation time-course. Furthermore, exogenous Wnt signalling in 3D adipogenic conditions inhibited differentiation compared to unstimulated controls. In addition, suppressing Wnt signalling by Dkk-1 restored and facilitated adipogenic differentiation in MSC spheroids. Our findings indicate that endogenous Wnt signalling is active and can be tracked in 3D MSC cultures where it may act as a molecular switch in adipogenesis. The identification of the signalling pathways that regulate MSCs in a 3D in vivo-like environment will advance our understanding of the molecular mechanisms that control MSC fate.

  10. A quality assessment of 3D video analysis for full scale rockfall experiments

    NASA Astrophysics Data System (ADS)

    Volkwein, A.; Glover, J.; Bourrier, F.; Gerber, W.

    2012-04-01

    Main goal of full scale rockfall experiments is to retrieve a 3D trajectory of a boulder along the slope. Such trajectories then can be used to calibrate rockfall simulation models. This contribution presents the application of video analysis techniques capturing rock fall velocity of some free fall full scale rockfall experiments along a rock face with an inclination of about 50 degrees. Different scaling methodologies have been evaluated. They mainly differ in the way the scaling factors between the movie frames and the reality and are determined. For this purpose some scale bars and targets with known dimensions have been distributed in advance along the slope. The single scaling approaches are briefly described as follows: (i) Image raster is scaled to the distant fixed scale bar then recalibrated to the plane of the passing rock boulder by taking the measured position of the nearest impact as the distance to the camera. The distance between the camera, scale bar, and passing boulder are surveyed. (ii) The image raster was scaled using the four nearest targets (identified using frontal video) from the trajectory to be analyzed. The average of the scaling factors was finally taken as scaling factor. (iii) The image raster was scaled using the four nearest targets from the trajectory to be analyzed. The scaling factor for one trajectory was calculated by balancing the mean scaling factors associated with the two nearest and the two farthest targets in relation to their mean distance to the analyzed trajectory. (iv) Same as previous method but with varying scaling factors during along the trajectory. It has shown that a direct measure of the scaling target and nearest impact zone is the most accurate. If constant plane is assumed it doesn't account for the lateral deviations of the rock boulder from the fall line consequently adding error into the analysis. Thus a combination of scaling methods (i) and (iv) are considered to give the best results. For best results

  11. Chlamydomonas cryopreparation methods for the 3-D analysis of cellular organelles.

    PubMed

    O'Toole, Eileen T

    2010-01-01

    Chlamydomonas reinhardtii is a popular model organism in modern cell biology. Historically, methods for preparing this cell for transmission electron microscopy have used conventional chemical fixation that can result in artifacts that affect the 3-D organization of the cell. We have developed improved methods of specimen preparation that involve high-pressure freezing followed by freeze-substitution that are particularly well suited for 3-D studies (O'Toole et al., 2003, 2007). In this chapter, we describe the details of our cryopreparation methods for the optimal preservation of whole cells for immunocytochemistry and electron tomography. Examples are presented that show the utility of this approach for studying the 3-D architecture of membrane systems and cytoskeletal arrays in intact cells.

  12. Nanoscale Analysis of a Hierarchical Hybrid Solar Cell in 3D

    PubMed Central

    Divitini, Giorgio; Stenzel, Ole; Ghadirzadeh, Ali; Guarnera, Simone; Russo, Valeria; Casari, Carlo S; Bassi, Andrea Li; Petrozza, Annamaria; Di Fonzo, Fabio; Schmidt, Volker; Ducati, Caterina

    2014-01-01

    A quantitative method for the characterization of nanoscale 3D morphology is applied to the investigation of a hybrid solar cell based on a novel hierarchical nanostructured photoanode. A cross section of the solar cell device is prepared by focused ion beam milling in a micropillar geometry, which allows a detailed 3D reconstruction of the titania photoanode by electron tomography. It is found that the hierarchical titania nanostructure facilitates polymer infiltration, thus favoring intermixing of the two semiconducting phases, essential for charge separation. The 3D nanoparticle network is analyzed with tools from stochastic geometry to extract information related to the charge transport in the hierarchical solar cell. In particular, the experimental dataset allows direct visualization of the percolation pathways that contribute to the photocurrent. PMID:25834481

  13. PRIMAS: a real-time 3D motion-analysis system

    NASA Astrophysics Data System (ADS)

    Sabel, Jan C.; van Veenendaal, Hans L. J.; Furnee, E. Hans

    1994-03-01

    The paper describes a CCD TV-camera-based system for real-time multicamera 2D detection of retro-reflective targets and software for accurate and fast 3D reconstruction. Applications of this system can be found in the fields of sports, biomechanics, rehabilitation research, and various other areas of science and industry. The new feature of real-time 3D opens an even broader perspective of application areas; animations in virtual reality are an interesting example. After presenting an overview of the hardware and the camera calibration method, the paper focuses on the real-time algorithms used for matching of the images and subsequent 3D reconstruction of marker positions. When using a calibrated setup of two cameras, it is now possible to track at least ten markers at 100 Hz. Limitations in the performance are determined by the visibility of the markers, which could be improved by adding a third camera.

  14. Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells

    PubMed Central

    Robinson, Benjamin K.; Cortes, Ernesto; Rice, Alistair J.; Sarper, Muge

    2016-01-01

    ABSTRACT Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment. PMID:27170254

  15. 3D numerical simulation analysis of passive drag near free surface in swimming

    NASA Astrophysics Data System (ADS)

    Zhan, Jie-min; Li, Tian-zeng; Chen, Xue-bin; Li, Yok-sheung; Wai, Wing-hong Onyx

    2015-04-01

    The aim of this work is to build a 3D numerical model to study the characteristics of passive drag on competitive swimmers taking into account the impact of the free surface. This model solves the 3D incompressible Navier-Stokes equations using RNG k- ɛ turbulence closure. The volume of fluid (VOF) method is used to locate the free surface. The 3D virtual model is created by Computer Aided Industrial Design (CAID) software, Rhinoceros. Firstly, a specific posture of swimming is studied. The simulation results are in good agreement with the data from mannequin towing experiments. The effects of a swimmer's arms and legs positions on swimming performance are then studied. Finally, it is demonstrated that the present method is capable of simulating gliding near the free surface.

  16. Analysis of Hyoid-Larynx Complex Using 3D Geometric Morphometrics.

    PubMed

    Loth, Anthony; Corny, Julien; Santini, Laure; Dahan, Laurie; Dessi, Patrick; Adalian, Pascal; Fakhry, Nicolas

    2015-06-01

    The aim of this study was to obtain a quantitative anatomical description of the hyoid bone-larynx complex using modern 3D reconstruction tools. The study was conducted on 104 bones from CT scan images of living adult subjects. Three-dimensional reconstructions were created from CT scan images using AVIZO 6.2 software package. A study of this complex was carried out using metric and morphological analyses. Characteristics of the hyoid bone and larynx were highly heterogeneous and were closely linked with the sex, height, and weight of the individuals. Height and width of larynx were significantly greater in men than in women (24.99 vs. 17.3 mm, p ≤ 0.05 and 46.75 vs. 41.07, p ≤ 0.05), whereas the thyroid angle was larger in females (81.12° vs. 74.48°, p ≤ 0.05). There was a significant correlation between the height and weight of subjects and different measurements of the hyoid-larynx complex. (Pearson's coefficient correlation r = 0.42, p ≤ 0.05 between the height of thyroid ala and the height of subjects and r = 0.1, p ≤ 0.05 between the height of thyroid ala and the weight of subjects). Shape and size analysis of the hyoid-larynx complex showed the existence of a significant sexual dimorphism and high interindividual heterogeneity depending to patient morphology. These results encourage us to go further with functional and imaging correlations.

  17. Noise analysis for near-field 3D FM-CW radar imaging systems

    NASA Astrophysics Data System (ADS)

    Sheen, David M.

    2015-05-01

    Near field radar imaging systems are used for demanding security applications including concealed weapon detection in airports and other high-security venues. Despite the near-field operation, phase noise and thermal noise can limit performance in several ways. Practical imaging systems can employ arrays with low gain antennas and relatively large signal distribution networks that have substantial losses which limit transmit power and increase the effective noise figure of the receiver chain, resulting in substantial thermal noise. Phase noise can also limit system performance. The signal coupled from transmitter to receiver is much larger than expected target signals. Phase noise from this coupled signal can set the system noise floor if the oscillator is too noisy. Frequency modulated continuous wave (FM-CW) radar transceivers used in short range systems are relatively immune to the effects of the coupled phase noise due to range correlation effects. This effect can reduce the phase-noise floor such that it is below the thermal noise floor for moderate performance oscillators. Phase noise is also manifested in the range response around bright targets, and can cause smaller targets to be obscured. Noise in synthetic aperture imaging systems is mitigated by the processing gain of the system. In this paper, the effects of thermal noise, phase noise, and processing gain are analyzed in the context of a near field 3-D FM-CW imaging radar as might be used for concealed weapon detection. In addition to traditional frequency domain analysis, a time-domain simulation is employed to graphically demonstrate the effect of these noise sources on a fast-chirping FM-CW system.

  18. 3-D seakeeping analysis with water on deck and slamming. Part 1: Numerical solver

    NASA Astrophysics Data System (ADS)

    Greco, M.; Lugni, C.

    2012-08-01

    A three-dimensional seakeeping numerical solver is developed to handle occurrence and effects of water-on-deck and bottom slamming. It couples (A) the rigid-ship motions with (B) the water flowing along the deck and (C) bottom slamming events. Problem A is studied with a 3-D weakly nonlinear potential flow solver based on the weak-scatterer hypothesis. Problem B, and so local and global induced green-water loads, are investigated by assuming shallow-water conditions onto the deck. Problem C is examined through a Wagner-type wedge-impact analysis. Within the coupling between A and B: the external seakeeping problem furnishes the initial and boundary conditions to the in-deck solver in terms of water level and velocity along the deck profile; in return the shallow-water problem makes available to the seakeeping solver the green-water loads to be introduced as additional loads into the rigid-motion equations. Within the coupling between A and C: the instantaneous ship configuration and its kinematic and dynamic conditions with respect to the incident waves will fix the parameters for the local impact problem; in return the slamming and water-entry pressures are integrated in the vessel region of interest and introduced as additional loads into the rigid-motion equations. The resulting numerical solver can study efficiently the ship interaction with regular and irregular sea states and the forward motion with limited speed of the vessel. This is crucial to perform reliable and feasible statistical investigations of vessel behavior. Main elements of the solver are described and validated against reference numerical solutions and model tests.

  19. F3D Image Processing and Analysis for Many - and Multi-core Platforms

    SciTech Connect

    2014-10-01

    F3D is written in OpenCL, so it achieve[sic] platform-portable parallelism on modern mutli-core CPUs and many-core GPUs. The interface and mechanims to access F3D core are written in Java as a plugin for Fiji/ImageJ to deliver several key image-processing algorithms necessary to remove artifacts from micro-tomography data. The algorithms consist of data parallel aware filters that can efficiently utilizes[sic] resources and can work on out of core datasets and scale efficiently across multiple accelerators. Optimizing for data parallel filters, streaming out of core datasets, and efficient resource and memory and data managements over complex execution sequence of filters greatly expedites any scientific workflow with image processing requirements. F3D performs several different types of 3D image processing operations, such as non-linear filtering using bilateral filtering and/or median filtering and/or morphological operators (MM). F3D gray-level MM operators are one-pass constant time methods that can perform morphological transformations with a line-structuring element oriented in discrete directions. Additionally, MM operators can be applied to gray-scale images, and consist of two parts: (a) a reference shape or structuring element, which is translated over the image, and (b) a mechanism, or operation, that defines the comparisons to be performed between the image and the structuring element. This tool provides a critical component within many complex pipelines such as those for performing automated segmentation of image stacks. F3D is also called a "descendent" of Quant-CT, another software we developed in the past. These two modules are to be integrated in a next version. Further details were reported in: D.M. Ushizima, T. Perciano, H. Krishnan, B. Loring, H. Bale, D. Parkinson, and J. Sethian. Structure recognition from high-resolution images of ceramic composites. IEEE International Conference on Big Data, October 2014.

  20. 3-D FEM field analysis in controlled-PM LSM for Maglev vehicle

    SciTech Connect

    Yoshida, Kinjiro; Lee, J.; Kim, Y.J.

    1997-03-01

    The magnetic fields in the controlled-PM LSM for Maglev vehicle, of which the width is not only finite with lateral edges, but also an effective electric-airgap is very large, are accurately analyzed by using 3-D FEM. The lateral airgap-flux due to lateral edges of the machine is made clear and its effects on thrust and lift forces are evaluated quantitatively from the comparison with 2-D FEA. The accuracy of 3-D FEA is verified by comparing the calculated results with the measured values.

  1. Feasibility study on 3-D shape analysis of high-aspect-ratio features using through-focus scanning optical microscopy

    PubMed Central

    Attota, Ravi Kiran; Weck, Peter; Kramar, John A.; Bunday, Benjamin; Vartanian, Victor

    2016-01-01

    In-line metrologies currently used in the semiconductor industry are being challenged by the aggressive pace of device scaling and the adoption of novel device architectures. Metrology and process control of three-dimensional (3-D) high-aspect-ratio (HAR) features are becoming increasingly important and also challenging. In this paper we present a feasibility study of through-focus scanning optical microscopy (TSOM) for 3-D shape analysis of HAR features. TSOM makes use of 3-D optical data collected using a conventional optical microscope for 3-D shape analysis. Simulation results of trenches and holes down to the 11 nm node are presented. The ability of TSOM to analyze an array of HAR features or a single isolated HAR feature is also presented. This allows for the use of targets with area over 100 times smaller than that of conventional gratings, saving valuable real estate on the wafers. Indications are that the sensitivity of TSOM may match or exceed the International Technology Roadmap for Semiconductors (ITRS) measurement requirements for the next several years. Both simulations and preliminary experimental results are presented. The simplicity, lowcost, high throughput, and nanometer scale 3-D shape sensitivity of TSOM make it an attractive inspection and process monitoring solution for nanomanufacturing. PMID:27464112

  2. A comparative analysis between active and passive techniques for underwater 3D reconstruction of close-range objects.

    PubMed

    Bianco, Gianfranco; Gallo, Alessandro; Bruno, Fabio; Muzzupappa, Maurizio

    2013-01-01

    In some application fields, such as underwater archaeology or marine biology, there is the need to collect three-dimensional, close-range data from objects that cannot be removed from their site. In particular, 3D imaging techniques are widely employed for close-range acquisitions in underwater environment. In this work we have compared in water two 3D imaging techniques based on active and passive approaches, respectively, and whole-field acquisition. The comparison is performed under poor visibility conditions, produced in the laboratory by suspending different quantities of clay in a water tank. For a fair comparison, a stereo configuration has been adopted for both the techniques, using the same setup, working distance, calibration, and objects. At the moment, the proposed setup is not suitable for real world applications, but it allowed us to conduct a preliminary analysis on the performances of the two techniques and to understand their capability to acquire 3D points in presence of turbidity. The performances have been evaluated in terms of accuracy and density of the acquired 3D points. Our results can be used as a reference for further comparisons in the analysis of other 3D techniques and algorithms. PMID:23966193

  3. Shaped 3D singular spectrum analysis for quantifying gene expression, with application to the early zebrafish embryo.

    PubMed

    Shlemov, Alex; Golyandina, Nina; Holloway, David; Spirov, Alexander

    2015-01-01

    Recent progress in microscopy technologies, biological markers, and automated processing methods is making