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Sample records for 3d qsar model

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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...

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  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. PMID:26202430

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  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. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  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 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Dataset Modelability by QSAR

    PubMed Central

    Golbraikh, Alexander; Muratov, Eugene; Fourches, Denis; Tropsha, Alexander

    2014-01-01

    We introduce a simple MODelability Index (MODI) that estimates the feasibility of obtaining predictive QSAR models (Correct Classification Rate above 0.7) for a binary dataset of bioactive compounds. MODI is defined as an activity class-weighted ratio of the number of the nearest neighbor pairs of compounds with the same activity class versus the total number of pairs. The MODI values were calculated for more than 100 datasets and the threshold of 0.65 was found to separate non-modelable from the modelable datasets. PMID:24251851

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Antioxidant QSAR modeling as exemplified on polyphenols.

    PubMed

    Lucić, Bono; Amić, Dragan; Trinajstić, Nenad

    2008-01-01

    Methodology for deriving quantitative structure-activity relationship (QSAR) models based on computed molecular descriptors, representing numerically structural features of polyphenols, and applicable to the antioxidant activity of polyphenols is delineated. The application of this methodology is illustrated on a data set of 100 polyphenols. Prior to the computation of molecular descriptors, molecular structures are coded in the SMILES form, a computer-acceptable version of structure, and then converted to the 3D form by the CORINA program. Using 3D structures, molecular descriptors can be calculated by one of several programs developed (we used the DRAGON program in this study). Finally, using computer program for selection of most important descriptors in the model, a two-descriptor model is selected and its use is illustrated.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  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. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Making Inexpensive 3-D Models

    ERIC Educational Resources Information Center

    Manos, Harry

    2016-01-01

    Visual aids are important to student learning, and they help make the teacher's job easier. Keeping with the "TPT" theme of "The Art, Craft, and Science of Physics Teaching," the purpose of this article is to show how teachers, lacking equipment and funds, can construct a durable 3-D model reference frame and a model gravity…

  1. 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).

  2. 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.

  3. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Making Inexpensive 3-D Models

    NASA Astrophysics Data System (ADS)

    Manos, Harry

    2016-03-01

    Visual aids are important to student learning, and they help make the teacher's job easier. Keeping with the TPT theme of "The Art, Craft, and Science of Physics Teaching," the purpose of this article is to show how teachers, lacking equipment and funds, can construct a durable 3-D model reference frame and a model gravity well tailored to specific class lessons. Most of the supplies are readily available in the home or at school: rubbing alcohol, a rag, two colors of spray paint, art brushes, and masking tape. The cost of these supplies, if you don't have them, is less than 20.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Crowdsourcing Based 3d Modeling

    NASA Astrophysics Data System (ADS)

    Somogyi, A.; Barsi, A.; Molnar, B.; Lovas, T.

    2016-06-01

    Web-based photo albums that support organizing and viewing the users' images are widely used. These services provide a convenient solution for storing, editing and sharing images. In many cases, the users attach geotags to the images in order to enable using them e.g. in location based applications on social networks. Our paper discusses a procedure that collects open access images from a site frequently visited by tourists. Geotagged pictures showing the image of a sight or tourist attraction are selected and processed in photogrammetric processing software that produces the 3D model of the captured object. For the particular investigation we selected three attractions in Budapest. To assess the geometrical accuracy, we used laser scanner and DSLR as well as smart phone photography to derive reference values to enable verifying the spatial model obtained from the web-album images. The investigation shows how detailed and accurate models could be derived applying photogrammetric processing software, simply by using images of the community, without visiting the site.

  17. 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

  18. 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

  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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. Hsp90 inhibitors, part 1: definition of 3-D QSAutogrid/R models as a tool for virtual screening.

    PubMed

    Ballante, Flavio; Caroli, Antonia; Wickersham, Richard B; Ragno, Rino

    2014-03-24

    The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation and stability of a variety of oncogenic signaling proteins. For this reason, Hsp90 has emerged as a promising target for anticancer drug development. Herein, we describe a complete computational procedure for building several 3-D QSAR models used as a ligand-based (LB) component of a comprehensive ligand-based (LB) and structure-based (SB) virtual screening (VS) protocol to identify novel molecular scaffolds of Hsp90 inhibitors. By the application of the 3-D QSAutogrid/R method, eight SB PLS 3-D QSAR models were generated, leading to a final multiprobe (MP) 3-D QSAR pharmacophoric model capable of recognizing the most significant chemical features for Hsp90 inhibition. Both the monoprobe and multiprobe models were optimized, cross-validated, and tested against an external test set. The obtained statistical results confirmed the models as robust and predictive to be used in a subsequent VS.

  6. 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.

  7. 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.

  8. QSAR Models for Regulatory Purposes: Experiences and Perspectives

    NASA Astrophysics Data System (ADS)

    Benfenati, Emilio

    Quantitative structure-activity relationships (QSARs) are more and more discussed and used in several situations. Their application to legislative purposes stimulated a large debate in Europe on the recent legislation on industrial chemicals. To correctly assess the suitability of QSAR, the discussion has to be done depending on the target. Different targets modify the model evaluation and use. The application of QSAR for legislative purposes requires keeping into account the use of the values obtained through the QSAR models. False negatives should be minimized. The model should be robust, verified, and validated. Reproducibility and transparency are other important characteristics.

  9. Structure-based ensemble-QSAR model: a novel approach to the study of the EGFR tyrosine kinase and its inhibitors

    PubMed Central

    Sun, Xian-qiang; Chen, Lei; Li, Yao-zong; Li, Wei-hua; Liu, Gui-xia; Tu, Yao-quan; Tang, Yun

    2014-01-01

    Aim: To develop a novel 3D-QSAR approach for study of the epidermal growth factor receptor tyrosine kinase (EGFR TK) and its inhibitors. Methods: One hundred thirty nine EGFR TK inhibitors were classified into 3 clusters. Ensemble docking of these inhibitors with 19 EGFR TK crystal structures was performed. Three protein structures that showed the best recognition of each cluster were selected based on the docking results. Then, a novel QSAR (ensemble-QSAR) building method was developed based on the ligand conformations determined by the corresponding protein structures. Results: Compared with the 3D-QSAR model, in which the ligand conformations were determined by a single protein structure, ensemble-QSAR exhibited higher R2 (0.87) and Q2 (0.78) values and thus appeared to be a more reliable and better predictive model. Ensemble-QSAR was also able to more accurately describe the interactions between the target and the ligands. Conclusion: The novel ensemble-QSAR model built in this study outperforms the traditional 3D-QSAR model in rationality, and provides a good example of selecting suitable protein structures for docking prediction and for building structure-based QSAR using available protein structures. PMID:24335842

  10. 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

  11. QSAR DataBank - an approach for the digital organization and archiving of QSAR model information

    PubMed Central

    2014-01-01

    Background Research efforts in the field of descriptive and predictive Quantitative Structure-Activity Relationships or Quantitative Structure–Property Relationships produce around one thousand scientific publications annually. All the materials and results are mainly communicated using printed media. The printed media in its present form have obvious limitations when they come to effectively representing mathematical models, including complex and non-linear, and large bodies of associated numerical chemical data. It is not supportive of secondary information extraction or reuse efforts while in silico studies poses additional requirements for accessibility, transparency and reproducibility of the research. This gap can and should be bridged by introducing domain-specific digital data exchange standards and tools. The current publication presents a formal specification of the quantitative structure-activity relationship data organization and archival format called the QSAR DataBank (QsarDB for shorter, or QDB for shortest). Results The article describes QsarDB data schema, which formalizes QSAR concepts (objects and relationships between them) and QsarDB data format, which formalizes their presentation for computer systems. The utility and benefits of QsarDB have been thoroughly tested by solving everyday QSAR and predictive modeling problems, with examples in the field of predictive toxicology, and can be applied for a wide variety of other endpoints. The work is accompanied with open source reference implementation and tools. Conclusions The proposed open data, open source, and open standards design is open to public and proprietary extensions on many levels. Selected use cases exemplify the benefits of the proposed QsarDB data format. General ideas for future development are discussed. PMID:24910716

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 3D Printing of Molecular Models

    ERIC Educational Resources Information Center

    Gardner, Adam; Olson, Arthur

    2016-01-01

    Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

  17. Predictive QSAR modeling workflow, model applicability domains, and virtual screening.

    PubMed

    Tropsha, Alexander; Golbraikh, Alexander

    2007-01-01

    Quantitative Structure Activity Relationship (QSAR) modeling has been traditionally applied as an evaluative approach, i.e., with the focus on developing retrospective and explanatory models of existing data. Model extrapolation was considered if only in hypothetical sense in terms of potential modifications of known biologically active chemicals that could improve compounds' activity. This critical review re-examines the strategy and the output of the modern QSAR modeling approaches. We provide examples and arguments suggesting that current methodologies may afford robust and validated models capable of accurate prediction of compound properties for molecules not included in the training sets. We discuss a data-analytical modeling workflow developed in our laboratory that incorporates modules for combinatorial QSAR model development (i.e., using all possible binary combinations of available descriptor sets and statistical data modeling techniques), rigorous model validation, and virtual screening of available chemical databases to identify novel biologically active compounds. Our approach places particular emphasis on model validation as well as the need to define model applicability domains in the chemistry space. We present examples of studies where the application of rigorously validated QSAR models to virtual screening identified computational hits that were confirmed by subsequent experimental investigations. The emerging focus of QSAR modeling on target property forecasting brings it forward as predictive, as opposed to evaluative, modeling approach.

  18. BEAMS3D Neutral Beam Injection Model

    SciTech Connect

    Lazerson, Samuel

    2014-04-14

    With the advent of applied 3D fi elds in Tokamaks and modern high performance stellarators, a need has arisen to address non-axisymmetric effects on neutral beam heating and fueling. We report on the development of a fully 3D neutral beam injection (NBI) model, BEAMS3D, which addresses this need by coupling 3D equilibria to a guiding center code capable of modeling neutral and charged particle trajectories across the separatrix and into the plasma core. Ionization, neutralization, charge-exchange, viscous velocity reduction, and pitch angle scattering are modeled with the ADAS atomic physics database [1]. Benchmark calculations are presented to validate the collisionless particle orbits, neutral beam injection model, frictional drag, and pitch angle scattering effects. A calculation of neutral beam heating in the NCSX device is performed, highlighting the capability of the code to handle 3D magnetic fields.

  19. VALIDATION OF IMPROVED 3D ATR MODEL

    SciTech Connect

    Soon Sam Kim; Bruce G. Schnitzler

    2005-11-01

    A full-core Monte Carlo based 3D model of the Advanced Test Reactor (ATR) was previously developed. [1] An improved 3D model has been developed by the International Criticality Safety Benchmark Evaluation Project (ICSBEP) to eliminate homogeneity of fuel plates of the old model, incorporate core changes into the new model, and to validate against a newer, more complicated core configuration. This new 3D model adds capability for fuel loading design and azimuthal power peaking studies of the ATR fuel elements.

  20. New public QSAR model for carcinogenicity

    PubMed Central

    2010-01-01

    Background One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fulfill the gaps in data concerned with properties of chemicals affecting the human health. (Q)SAR models are accepted as a suitable source of information. The EU funded CAESAR project aimed to develop models for prediction of 5 endpoints for regulatory purposes. Carcinogenicity is one of the endpoints under consideration. Results Models for prediction of carcinogenic potency according to specific requirements of Chemical regulation were developed. The dataset of 805 non-congeneric chemicals extracted from Carcinogenic Potency Database (CPDBAS) was used. Counter Propagation Artificial Neural Network (CP ANN) algorithm was implemented. In the article two alternative models for prediction carcinogenicity are described. The first model employed eight MDL descriptors (model A) and the second one twelve Dragon descriptors (model B). CAESAR's models have been assessed according to the OECD principles for the validation of QSAR. For the model validity we used a wide series of statistical checks. Models A and B yielded accuracy of training set (644 compounds) equal to 91% and 89% correspondingly; the accuracy of the test set (161 compounds) was 73% and 69%, while the specificity was 69% and 61%, respectively. Sensitivity in both cases was equal to 75%. The accuracy of the leave 20% out cross validation for the training set of models A and B was equal to 66% and 62% respectively. To verify if the models perform correctly on new compounds the external validation was carried out. The external test set was composed of 738 compounds. We obtained accuracy of external validation equal to 61.4% and 60.0%, sensitivity 64.0% and 61.8% and specificity equal to 58.9% and 58.4% respectively for models A and B. Conclusion Carcinogenicity is a particularly important endpoint and it is expected that QSAR models will not replace the human experts opinions

  1. Modeling Cellular Processes in 3-D

    PubMed Central

    Mogilner, Alex; Odde, David

    2011-01-01

    Summary Recent advances in photonic imaging and fluorescent protein technology offer unprecedented views of molecular space-time dynamics in living cells. At the same time, advances in computing hardware and software enable modeling of ever more complex systems, from global climate to cell division. As modeling and experiment become more closely integrated, we must address the issue of modeling cellular processes in 3-D. Here, we highlight recent advances related to 3-D modeling in cell biology. While some processes require full 3-D analysis, we suggest that others are more naturally described in 2-D or 1-D. Keeping the dimensionality as low as possible reduces computational time and makes models more intuitively comprehensible; however, the ability to test full 3-D models will build greater confidence in models generally and remains an important emerging area of cell biological modeling. PMID:22036197

  2. 3D facial expression modeling for recognition

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoguang; Jain, Anil K.; Dass, Sarat C.

    2005-03-01

    Current two-dimensional image based face recognition systems encounter difficulties with large variations in facial appearance due to the pose, illumination and expression changes. Utilizing 3D information of human faces is promising for handling the pose and lighting variations. While the 3D shape of a face does not change due to head pose (rigid) and lighting changes, it is not invariant to the non-rigid facial movement and evolution, such as expressions and aging effect. We propose a facial surface matching framework to match multiview facial scans to a 3D face model, where the (non-rigid) expression deformation is explicitly modeled for each subject, resulting in a person-specific deformation model. The thin plate spline (TPS) is applied to model the deformation based on the facial landmarks. The deformation is applied to the 3D neutral expression face model to synthesize the corresponding expression. Both the neutral and the synthesized 3D surface models are used to match a test scan. The surface registration and matching between a test scan and a 3D model are achieved by a modified Iterative Closest Point (ICP) algorithm. Preliminary experimental results demonstrate that the proposed expression modeling and recognition-by-synthesis schemes improve the 3D matching accuracy.

  3. Energy-Based Pharmacophore and Three-Dimensional Quantitative Structure--Activity Relationship (3D-QSAR) Modeling Combined with Virtual Screening To Identify Novel Small-Molecule Inhibitors of Silent Mating-Type Information Regulation 2 Homologue 1 (SIRT1).

    PubMed

    Pulla, Venkat Koushik; Sriram, Dinavahi Saketh; Viswanadha, Srikant; Sriram, Dharmarajan; Yogeeswari, Perumal

    2016-01-25

    Silent mating-type information regulation 2 homologue 1 (SIRT1), being the homologous enzyme of silent information regulator-2 gene in yeast, has multifaceted functions. It deacetylates a wide range of histone and nonhistone proteins; hence, it has good therapeutic importance. SIRT1 was believed to be overexpressed in many cancers (prostate, colon) and inflammatory disorders (rheumatoid arthritis). Hence, designing inhibitors against SIRT1 could be considered valuable. Both structure-based and ligand-based drug design strategies were employed to design novel inhibitors utilizing high-throughput virtual screening of chemical databases. An energy-based pharmacophore was generated using the crystal structure of SIRT1 bound with a small molecule inhibitor and compared with a ligand-based pharmacophore model that showed four similar features. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed and validated to be employed in the virtual screening protocol. Among the designed compounds, Lead 17 emerged as a promising SIRT1 inhibitor with IC50 of 4.34 μM and, at nanomolar concentration (360 nM), attenuated the proliferation of prostate cancer cells (LnCAP). In addition, Lead 17 significantly reduced production of reactive oxygen species, thereby reducing pro inflammatory cytokines such as IL6 and TNF-α. Furthermore, the anti-inflammatory potential of the compound was ascertained using an animal paw inflammation model induced by carrageenan. Thus, the identified SIRT1 inhibitors could be considered as potent leads to treat both cancer and inflammation.

  4. Energy-Based Pharmacophore and Three-Dimensional Quantitative Structure--Activity Relationship (3D-QSAR) Modeling Combined with Virtual Screening To Identify Novel Small-Molecule Inhibitors of Silent Mating-Type Information Regulation 2 Homologue 1 (SIRT1).

    PubMed

    Pulla, Venkat Koushik; Sriram, Dinavahi Saketh; Viswanadha, Srikant; Sriram, Dharmarajan; Yogeeswari, Perumal

    2016-01-25

    Silent mating-type information regulation 2 homologue 1 (SIRT1), being the homologous enzyme of silent information regulator-2 gene in yeast, has multifaceted functions. It deacetylates a wide range of histone and nonhistone proteins; hence, it has good therapeutic importance. SIRT1 was believed to be overexpressed in many cancers (prostate, colon) and inflammatory disorders (rheumatoid arthritis). Hence, designing inhibitors against SIRT1 could be considered valuable. Both structure-based and ligand-based drug design strategies were employed to design novel inhibitors utilizing high-throughput virtual screening of chemical databases. An energy-based pharmacophore was generated using the crystal structure of SIRT1 bound with a small molecule inhibitor and compared with a ligand-based pharmacophore model that showed four similar features. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed and validated to be employed in the virtual screening protocol. Among the designed compounds, Lead 17 emerged as a promising SIRT1 inhibitor with IC50 of 4.34 μM and, at nanomolar concentration (360 nM), attenuated the proliferation of prostate cancer cells (LnCAP). In addition, Lead 17 significantly reduced production of reactive oxygen species, thereby reducing pro inflammatory cytokines such as IL6 and TNF-α. Furthermore, the anti-inflammatory potential of the compound was ascertained using an animal paw inflammation model induced by carrageenan. Thus, the identified SIRT1 inhibitors could be considered as potent leads to treat both cancer and inflammation. PMID:26636371

  5. 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.

  6. Digital relief generation from 3D models

    NASA Astrophysics Data System (ADS)

    Wang, Meili; Sun, Yu; Zhang, Hongming; Qian, Kun; Chang, Jian; He, Dongjian

    2016-09-01

    It is difficult to extend image-based relief generation to high-relief generation, as the images contain insufficient height information. To generate reliefs from three-dimensional (3D) models, it is necessary to extract the height fields from the model, but this can only generate bas-reliefs. To overcome this problem, an efficient method is proposed to generate bas-reliefs and high-reliefs directly from 3D meshes. To produce relief features that are visually appropriate, the 3D meshes are first scaled. 3D unsharp masking is used to enhance the visual features in the 3D mesh, and average smoothing and Laplacian smoothing are implemented to achieve better smoothing results. A nonlinear variable scaling scheme is then employed to generate the final bas-reliefs and high-reliefs. Using the proposed method, relief models can be generated from arbitrary viewing positions with different gestures and combinations of multiple 3D models. The generated relief models can be printed by 3D printers. The proposed method provides a means of generating both high-reliefs and bas-reliefs in an efficient and effective way under the appropriate scaling factors.

  7. NUBEAM developments and 3d halo modeling

    NASA Astrophysics Data System (ADS)

    Gorelenkova, M. V.; Medley, S. S.; Kaye, S. M.

    2012-10-01

    Recent developments related to the 3D halo model in NUBEAM code are described. To have a reliable halo neutral source for diagnostic simulation, the TRANSP/NUBEAM code has been enhanced with full implementation of ADAS atomic physic ground state and excited state data for hydrogenic beams and mixed species plasma targets. The ADAS codes and database provide the density and temperature dependence of the atomic data, and the collective nature of the state excitation process. To be able to populate 3D halo output with sufficient statistical resolution, the capability to control the statistics of fast ion CX modeling and for thermal halo launch has been added to NUBEAM. The 3D halo neutral model is based on modification and extension of the ``beam in box'' aligned 3d Cartesian grid that includes the neutral beam itself, 3D fast neutral densities due to CX of partially slowed down fast ions in the beam halo region, 3D thermal neutral densities due to CX deposition and fast neutral recapture source. More details on the 3D halo simulation design will be presented.

  8. Nanomaterials - the Next Great Challenge for Qsar Modelers

    NASA Astrophysics Data System (ADS)

    Puzyn, Tomasz; Gajewicz, Agnieszka; Leszczynska, Danuta; Leszczynski, Jerzy

    In this final chapter a new perspective for the application of QSAR in the nanosciences is discussed. The role of nanomaterials is rapidly increasing in many aspects of everyday life. This is promoting a wide range of research needs related to both the design of new materials with required properties and performing a comprehensive risk assessment of the manufactured nanoparticles. The development of nanoscience also opens new areas for QSAR modelers. We have begun this contribution with a detailed discussion on the remarkable physical-chemical properties of nanomaterials and their specific toxicities. Both these factors should be considered as potential endpoints for further nano-QSAR studies. Then, we have highlighted the status and research needs in the area of molecular descriptors applicable to nanomaterials. Finally, we have put together currently available nano-QSAR models related to the physico-chemical endpoints of nanoparticles and their activity. Although we have observed many problems (i.e., a lack of experimental data, insufficient and inadequate descriptors), we do believe that application of QSAR methodology will significantly support nanoscience in the near future. Development of reliable nano-QSARs can be considered as the next challenging task for the QSAR community.

  9. The CIFIST 3D model atmosphere grid.

    NASA Astrophysics Data System (ADS)

    Ludwig, H.-G.; Caffau, E.; Steffen, M.; Freytag, B.; Bonifacio, P.; Kučinskas, A.

    Grids of stellar atmosphere models and associated synthetic spectra are numerical products which have a large impact in astronomy due to their ubiquitous application in the interpretation of radiation from individual stars and stellar populations. 3D model atmospheres are now on the verge of becoming generally available for a wide range of stellar atmospheric parameters. We report on efforts to develop a grid of 3D model atmospheres for late-type stars within the CIFIST Team at Paris Observatory. The substantial demands in computational and human labor for the model production and post-processing render this apparently mundane task a challenging logistic exercise. At the moment the CIFIST grid comprises 77 3D model atmospheres with emphasis on dwarfs of solar and sub-solar metallicities. While the model production is still ongoing, first applications are already worked upon by the CIFIST Team and collaborators.

  10. Using Toxicological Evidence from QSAR Models in Practice

    EPA Science Inventory

    The new generation of QSAR models provides supporting documentation in addition to the predicted toxicological value. Such information enables the toxicologist to explore the properties of chemical substances and to review and increase the reliability of toxicity predictions. Thi...

  11. 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

  12. 3D Modeling Engine Representation Summary Report

    SciTech Connect

    Steven Prescott; Ramprasad Sampath; Curtis Smith; Timothy Yang

    2014-09-01

    Computers have been used for 3D modeling and simulation, but only recently have computational resources been able to give realistic results in a reasonable time frame for large complex models. This summary report addressed the methods, techniques, and resources used to develop a 3D modeling engine to represent risk analysis simulation for advanced small modular reactor structures and components. The simulations done for this evaluation were focused on external events, specifically tsunami floods, for a hypothetical nuclear power facility on a coastline.

  13. BEAMS3D Neutral Beam Injection Model

    NASA Astrophysics Data System (ADS)

    McMillan, Matthew; Lazerson, Samuel A.

    2014-09-01

    With the advent of applied 3D fields in Tokamaks and modern high performance stellarators, a need has arisen to address non-axisymmetric effects on neutral beam heating and fueling. We report on the development of a fully 3D neutral beam injection (NBI) model, BEAMS3D, which addresses this need by coupling 3D equilibria to a guiding center code capable of modeling neutral and charged particle trajectories across the separatrix and into the plasma core. Ionization, neutralization, charge-exchange, viscous slowing down, and pitch angle scattering are modeled with the ADAS atomic physics database. Elementary benchmark calculations are presented to verify the collisionless particle orbits, NBI model, frictional drag, and pitch angle scattering effects. A calculation of neutral beam heating in the NCSX device is performed, highlighting the capability of the code to handle 3D magnetic fields. Notice: this manuscript has been authored by Princeton University under Contract Number DE-AC02-09CH11466 with the US Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

  14. 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.

  15. 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.

  16. Evolution of Archaea in 3D modeling

    NASA Astrophysics Data System (ADS)

    Pikuta, Elena V.; Tankosic, Dragana; Sheldon, Rob

    2012-11-01

    The analysis of all groups of Archaea performed in two-dimensions have demonstrated a specific distribution of Archaean species as a function of pH/temperature, temperature/salinity and pH/salinity. Work presented here is an extension of this analysis with a three dimensional (3D) modeling in logarithmic scale. As it was shown in 2D representation, the "Rules of the Diagonal" have been expressed even more clearly in 3D modeling. In this article, we used a 3D Mesh modeling to show the range of distribution of each separate group of Archaea as a function of pH, temperature, and salinity. Visible overlap and links between different groups indicate a direction of evolution in Archaea. The major direction in ancestral life (vector of evolution) has been indicated: from high temperature, acidic, and low-salinity system towards low temperature, alkaline and high salinity systems. Specifics of the geometrical coordinates and distribution of separate groups of Archaea in 3 D scale were analyzed with a mathematical description of the functions. Based on the obtained data, a new model for the origin and evolution of life on Earth is proposed. The geometry of this model is described by a hyperboloid of one sheet. Conclusions of this research are consistent with previous results derived from the two-dimensional diagrams. This approach is suggested as a new method for analyzing any biological group in accordance to its environmental parameters.

  17. 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.

  18. 3-D Teaching Models for All

    ERIC Educational Resources Information Center

    Bradley, Joan; Farland-Smith, Donna

    2010-01-01

    Allowing a student to "see" through touch what other students see through a microscope can be a challenging task. Therefore, author Joan Bradley created three-dimensional (3-D) models with one student's visual impairment in mind. They are meant to benefit all students and can be used to teach common high school biology topics, including the…

  19. 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.

  20. Microfluidic 3D models of cancer

    PubMed Central

    Sung, Kyung Eun; Beebe, David J.

    2014-01-01

    Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneity of tumors and their microenvironment make it challenging to both study and treat cancer. Traditional animal cancer models and in vitro cancer models are limited in their ability to recapitulate human structures and functions, thus hindering the identification of appropriate drug targets and therapeutic strategies. The development and application of microfluidic 3D cancer models has the potential to overcome some of the limitations inherent to traditional models. This review summarizes the progress in microfluidic 3D cancer models, their benefits, and their broad application to basic cancer biology, drug screening, and drug discovery. PMID:25017040

  1. Microfluidic 3D models of cancer.

    PubMed

    Sung, Kyung Eun; Beebe, David J

    2014-12-15

    Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneity of tumors and their microenvironment make it challenging to both study and treat cancer. Traditional animal cancer models and in vitro cancer models are limited in their ability to recapitulate human structures and functions, thus hindering the identification of appropriate drug targets and therapeutic strategies. The development and application of microfluidic 3D cancer models have the potential to overcome some of the limitations inherent to traditional models. This review summarizes the progress in microfluidic 3D cancer models, their benefits, and their broad application to basic cancer biology, drug screening, and drug discovery.

  2. Do-It-Yourself: 3D Models of Hydrogenic Orbitals through 3D Printing

    ERIC Educational Resources Information Center

    Griffith, Kaitlyn M.; de Cataldo, Riccardo; Fogarty, Keir H.

    2016-01-01

    Introductory chemistry students often have difficulty visualizing the 3-dimensional shapes of the hydrogenic electron orbitals without the aid of physical 3D models. Unfortunately, commercially available models can be quite expensive. 3D printing offers a solution for producing models of hydrogenic orbitals. 3D printing technology is widely…

  3. Debris Dispersion Model Using Java 3D

    NASA Technical Reports Server (NTRS)

    Thirumalainambi, Rajkumar; Bardina, Jorge

    2004-01-01

    This paper describes web based simulation of Shuttle launch operations and debris dispersion. Java 3D graphics provides geometric and visual content with suitable mathematical model and behaviors of Shuttle launch. Because the model is so heterogeneous and interrelated with various factors, 3D graphics combined with physical models provides mechanisms to understand the complexity of launch and range operations. The main focus in the modeling and simulation covers orbital dynamics and range safety. Range safety areas include destruct limit lines, telemetry and tracking and population risk near range. If there is an explosion of Shuttle during launch, debris dispersion is explained. The shuttle launch and range operations in this paper are discussed based on the operations from Kennedy Space Center, Florida, USA.

  4. Monte Carlo QSAR models for predicting organophosphate inhibition of acetycholinesterase.

    PubMed

    Veselinović, J B; Nikolić, G M; Trutić, N V; Živković, J V; Veselinović, A M

    2015-06-01

    A series of 278 organophosphate compounds acting as acetylcholinesterase inhibitors has been studied. The Monte Carlo method was used as a tool for building up one-variable quantitative structure-activity relationship (QSAR) models for acetylcholinesterase inhibition activity based on the principle that the target endpoint is treated as a random event. As an activity, bimolecular rate constants were used. The QSAR models were based on optimal descriptors obtained from Simplified Molecular Input-Line Entry System (SMILES) used for the representation of molecular structure. Two modelling approaches were examined: (1) 'classic' training-test system where the QSAR model was built with one random split into a training, test and validation set; and (2) the correlation balance based QSAR models were built with two random splits into a sub-training, calibration, test and validation set. The DModX method was used for defining the applicability domain. The obtained results suggest that studied activity can be determined with the application of QSAR models calculated with the Monte Carlo method since the statistical quality of all build models was very good. Finally, structural indicators for the increase and the decrease of the bimolecular rate constant are defined. The possibility of using these results for the computer-aided design of new organophosphate compounds is presented.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. Collaborative annotation of 3D crystallographic models.

    PubMed

    Hunter, J; Henderson, M; Khan, I

    2007-01-01

    This paper describes the AnnoCryst system-a tool that was designed to enable authenticated collaborators to share online discussions about 3D crystallographic structures through the asynchronous attachment, storage, and retrieval of annotations. Annotations are personal comments, interpretations, questions, assessments, or references that can be attached to files, data, digital objects, or Web pages. The AnnoCryst system enables annotations to be attached to 3D crystallographic models retrieved from either private local repositories (e.g., Fedora) or public online databases (e.g., Protein Data Bank or Inorganic Crystal Structure Database) via a Web browser. The system uses the Jmol plugin for viewing and manipulating the 3D crystal structures but extends Jmol by providing an additional interface through which annotations can be created, attached, stored, searched, browsed, and retrieved. The annotations are stored on a standardized Web annotation server (Annotea), which has been extended to support 3D macromolecular structures. Finally, the system is embedded within a security framework that is capable of authenticating users and restricting access only to trusted colleagues.

  10. On the development and validation of QSAR models.

    PubMed

    Gramatica, Paola

    2013-01-01

    The fundamental and more critical steps that are necessary for the development and validation of QSAR models are presented in this chapter as best practices in the field. These procedures are discussed in the context of predictive QSAR modelling that is focused on achieving models of the highest statistical quality and with external predictive power. The most important and most used statistical parameters needed to verify the real performances of QSAR models (of both linear regression and classification) are presented. Special emphasis is placed on the validation of models, both internally and externally, as well as on the need to define model applicability domains, which should be done when models are employed for the prediction of new external compounds.

  11. Prediction of Intracellular Localization of Fluorescent Dyes Using QSAR Models.

    PubMed

    Uchinomiya, Shohei; Horobin, Richard W; Alvarado-Martínez, Enrique; Peña-Cabrera, Eduardo; Chang, Young-Tae

    2016-01-01

    Control of fluorescent dye localization in live cells is crucial for fluorescence imaging. Here, we describe quantitative structure activity relation (QSAR) models for predicting intracellular localization of fluorescent dyes. For generating the QSAR models, electric charge (Z) calculated by pKa, conjugated bond number (CBN), the largest conjugated fragment (LCF), molecular weight (MW) and log P were used as parameters. We identified the intracellular localization of 119 BODIPY dyes in live NIH3T3 cells, and assessed the accuracy of our models by comparing their predictions with the observed dye localizations. As predicted by the models, no BODIPY dyes localized in nuclei or plasma membranes. The accuracy of the model for localization in fat droplets was 92%, with the models for cytosol and lysosomes showing poorer agreement with observed dye localization, albeit well above chance levels. Overall therefore the utility of QSAR models for predicting dye localization in live cells was clearly demonstrated. PMID:27055752

  12. 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

  13. 3-D model-based vehicle tracking.

    PubMed

    Lou, Jianguang; Tan, Tieniu; Hu, Weiming; Yang, Hao; Maybank, Steven J

    2005-10-01

    This paper aims at tracking vehicles from monocular intensity image sequences and presents an efficient and robust approach to three-dimensional (3-D) model-based vehicle tracking. Under the weak perspective assumption and the ground-plane constraint, the movements of model projection in the two-dimensional image plane can be decomposed into two motions: translation and rotation. They are the results of the corresponding movements of 3-D translation on the ground plane (GP) and rotation around the normal of the GP, which can be determined separately. A new metric based on point-to-line segment distance is proposed to evaluate the similarity between an image region and an instantiation of a 3-D vehicle model under a given pose. Based on this, we provide an efficient pose refinement method to refine the vehicle's pose parameters. An improved EKF is also proposed to track and to predict vehicle motion with a precise kinematics model. Experimental results with both indoor and outdoor data show that the algorithm obtains desirable performance even under severe occlusion and clutter.

  14. 3-D model-based vehicle tracking.

    PubMed

    Lou, Jianguang; Tan, Tieniu; Hu, Weiming; Yang, Hao; Maybank, Steven J

    2005-10-01

    This paper aims at tracking vehicles from monocular intensity image sequences and presents an efficient and robust approach to three-dimensional (3-D) model-based vehicle tracking. Under the weak perspective assumption and the ground-plane constraint, the movements of model projection in the two-dimensional image plane can be decomposed into two motions: translation and rotation. They are the results of the corresponding movements of 3-D translation on the ground plane (GP) and rotation around the normal of the GP, which can be determined separately. A new metric based on point-to-line segment distance is proposed to evaluate the similarity between an image region and an instantiation of a 3-D vehicle model under a given pose. Based on this, we provide an efficient pose refinement method to refine the vehicle's pose parameters. An improved EKF is also proposed to track and to predict vehicle motion with a precise kinematics model. Experimental results with both indoor and outdoor data show that the algorithm obtains desirable performance even under severe occlusion and clutter. PMID:16238061

  15. Sensing and compressing 3-D models

    SciTech Connect

    Krumm, J.

    1998-02-01

    The goal of this research project was to create a passive and robust computer vision system for producing 3-D computer models of arbitrary scenes. Although the authors were unsuccessful in achieving the overall goal, several components of this research have shown significant potential. Of particular interest is the application of parametric eigenspace methods for planar pose measurement of partially occluded objects in gray-level images. The techniques presented provide a simple, accurate, and robust solution to the planar pose measurement problem. In addition, the representational efficiency of eigenspace methods used with gray-level features were successfully extended to binary features, which are less sensitive to illumination changes. The results of this research are presented in two papers that were written during the course of this project. The papers are included in sections 2 and 3. The first section of this report summarizes the 3-D modeling efforts.

  16. Robust hashing for 3D models

    NASA Astrophysics Data System (ADS)

    Berchtold, Waldemar; Schäfer, Marcel; Rettig, Michael; Steinebach, Martin

    2014-02-01

    3D models and applications are of utmost interest in both science and industry. With the increment of their usage, their number and thereby the challenge to correctly identify them increases. Content identification is commonly done by cryptographic hashes. However, they fail as a solution in application scenarios such as computer aided design (CAD), scientific visualization or video games, because even the smallest alteration of the 3D model, e.g. conversion or compression operations, massively changes the cryptographic hash as well. Therefore, this work presents a robust hashing algorithm for 3D mesh data. The algorithm applies several different bit extraction methods. They are built to resist desired alterations of the model as well as malicious attacks intending to prevent correct allocation. The different bit extraction methods are tested against each other and, as far as possible, the hashing algorithm is compared to the state of the art. The parameters tested are robustness, security and runtime performance as well as False Acceptance Rate (FAR) and False Rejection Rate (FRR), also the probability calculation of hash collision is included. The introduced hashing algorithm is kept adaptive e.g. in hash length, to serve as a proper tool for all applications in practice.

  17. QSAR models for anti-malarial activity of 4-aminoquinolines.

    PubMed

    Masand, Vijay H; Toropov, Andrey A; Toropova, Alla P; Mahajan, Devidas T

    2014-03-01

    In the present study, predictive quantitative structure - activity relationship (QSAR) models for anti-malarial activity of 4-aminoquinolines have been developed. CORAL, which is freely available on internet (http://www.insilico.eu/coral), has been used as a tool of QSAR analysis to establish statistically robust QSAR model of anti-malarial activity of 4-aminoquinolines. Six random splits into the visible sub-system of the training and invisible subsystem of validation were examined. Statistical qualities for these splits vary, but in all these cases, statistical quality of prediction for anti-malarial activity was quite good. The optimal SMILES-based descriptor was used to derive the single descriptor based QSAR model for a data set of 112 aminoquinolones. All the splits had r(2)> 0.85 and r(2)> 0.78 for subtraining and validation sets, respectively. The three parametric multilinear regression (MLR) QSAR model has Q(2) = 0.83, R(2) = 0.84 and F = 190.39. The anti-malarial activity has strong correlation with presence/absence of nitrogen and oxygen at a topological distance of six. PMID:24801104

  18. Fallon FORGE 3D Geologic Model

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

    An x,y,z scattered data file for the 3D geologic model of the Fallon FORGE site. Model created in Earthvision by Dynamic Graphic Inc. The model was constructed with a grid spacing of 100 m. Geologic surfaces were extrapolated from the input data using a minimum tension gridding algorithm. The data file is tabular data in a text file, with lithology data associated with X,Y,Z grid points. All the relevant information is in the file header (the spatial reference, the projection etc.) In addition all the fields in the data file are identified in the header.

  19. 3D Models of Symbiotic Binaries

    NASA Astrophysics Data System (ADS)

    Mohamed, S.; Booth, R.; Podsiadlowski, Ph.; Ramstedt, S.; Vlemmings, W.; Maercker, M.

    2015-12-01

    Symbiotic binaries consist of a cool, mass-losing giant and an accreting, compact companion. We present 3D Smoothed Particle Hydrodynamics (SPH) models of two such interacting binaries, RS Oph and Mira AB. RS Oph is also a recurrent nova system, thus we model multiple quiescent mass transfer-nova outburst cycles. The resulting circumstellar structures of both systems are highly complex with the formation of spirals, arcs, shells, equatorial and bipolar outflows. We compare the models to recent observations and discuss the implications of our results for related systems, e.g., bipolar nebulae and jets, chemically peculiar stars, and the progenitors of Type Ia supernovae.

  20. QSAR Models at the US FDA/NCTR.

    PubMed

    Hong, Huixiao; Chen, Minjun; Ng, Hui Wen; Tong, Weida

    2016-01-01

    Quantitative structure-activity relationship (QSAR) has been used in the scientific research community for many decades and applied to drug discovery and development in the industry. QSAR technologies are advancing fast and attracting possible applications in regulatory science. To facilitate the development of reliable QSAR models, the FDA had invested a lot of efforts in constructing chemical databases with a variety of efficacy and safety endpoint data, as well as in the development of computational algorithms. In this chapter, we briefly describe some of the often used databases developed at the FDA such as EDKB (Endocrine Disruptor Knowledge Base), EADB (Estrogenic Activity Database), LTKB (Liver Toxicity Knowledge Base), and CERES (Chemical Evaluation and Risk Estimation System) and the technologies adopted by the agency such as Mold(2) program for calculation of a large and diverse set of molecular descriptors and decision forest algorithm for QSAR model development. We also summarize some QSAR models that have been developed for safety evaluation of the FDA-regulated products. PMID:27311476

  1. 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.

  2. 3D model of bow shocks

    NASA Astrophysics Data System (ADS)

    Gustafsson, M.; Ravkilde, T.; Kristensen, L. E.; Cabrit, S.; Field, D.; Pineau Des Forêts, G.

    2010-04-01

    Context. Shocks produced by outflows from young stars are often observed as bow-shaped structures in which the H2 line strength and morphology are characteristic of the physical and chemical environments and the velocity of the impact. Aims: We present a 3D model of interstellar bow shocks propagating in a homogeneous molecular medium with a uniform magnetic field. The model enables us to estimate the shock conditions in observed flows. As an example, we show how the model can reproduce rovibrational H2 observations of a bow shock in OMC1. Methods: The 3D model is constructed by associating a planar shock with every point on a 3D bow skeleton. The planar shocks are modelled with a highly sophisticated chemical reaction network that is essential for predicting accurate shock widths and line emissions. The shock conditions vary along the bow surface and determine the shock type, the local thickness, and brightness of the bow shell. The motion of the cooling gas parallel to the bow surface is also considered. The bow shock can move at an arbitrary inclination to the magnetic field and to the observer, and we model the projected morphology and radial velocity distribution in the plane-of-sky. Results: The morphology of a bow shock is highly dependent on the orientation of the magnetic field and the inclination of the flow. Bow shocks can appear in many different guises and do not necessarily show a characteristic bow shape. The ratio of the H2 v = 2-1 S(1) line to the v = 1-0 S(1) line is variable across the flow and the spatial offset between the peaks of the lines may be used to estimate the inclination of the flow. The radial velocity comes to a maximum behind the apparent apex of the bow shock when the flow is seen at an inclination different from face-on. Under certain circumstances the radial velocity of an expanding bow shock can show the same signatures as a rotating flow. In this case a velocity gradient perpendicular to the outflow direction is a projection

  3. 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.

  4. 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.

  5. QSAR in predictive models for ecological risk assessment

    SciTech Connect

    Passino-Reader, D.R.; Hickey, J.P.

    1994-12-31

    The end use of toxicity and exposure data is risk assessment to determine the probability that receptors experience harmful effects from exposure to environmental contaminants at a site. Determination of processes and development of predictive models precede the collection of data for risk assessment. The presence of hundreds of contaminants at a site and absence of data for many contaminants lead to the use of QSAR to implement the models. Examples of the use of linear salvation energy relationships (LSER) to provide estimates of aquatic toxicity and exposure endpoints will be provided. Integration of QSAR estimates and measured data must be addressed in the uncertainty analysis accompanying ecological risk assessment.

  6. Composite model of a 3-D image

    NASA Technical Reports Server (NTRS)

    Dukhovich, I. J.

    1980-01-01

    This paper presents a composite model of a moving (3-D) image especially useful for the sequential image processing and encoding. A non-linear predictor based on the composite model is described. The performance of this predictor is used as a measure of the validity of the model for a real image source. The minimization of a total mean square prediction error provides an inequality which determines a condition for the profitable use of the composite model and can serve as a decision device for the selection of the number of subsources within the model. The paper also describes statistical properties of the prediction error and contains results of computer simulation of two non-linear predictors in the case of perfect classification between subsources.

  7. 3D Model of Surfactant Replacement Therapy

    NASA Astrophysics Data System (ADS)

    Grotberg, James; Tai, Cheng-Feng; Filoche, Marcel

    2015-11-01

    Surfactant Replacement Therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. Though successful in neonatal applications, its use in adults had early success followed by failure. We present the first mathematical model of 3D SRT where a liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug first deposits a coating film on the airway wall which subtracts from its volume, a ``coating cost''. Then the plug splits unevenly at the airway bifurcation due to gravity. The steps are repeated until a plug ruptures or reaches the tree endpoint alveoli/acinus. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published literature, the earlier successful adult SRT studies show comparatively good index values, while the later failed studies do not. Those unsuccessful studies used smaller dose volumes with higher concentration mixtures, apparently assuming a well mixed compartment. The model shows that adult lungs are not well mixed in SRT due to the coating cost and gravity effects. Returning to the higher dose volume protocols could save many thousands of lives annually in the US. Supported by NIH Grants HL85156, HL84370 and Agence Nationale de la Recherche, ANR no. 2010-BLAN-1119-05.

  8. MOSSFRAC: An anisotropic 3D fracture model

    SciTech Connect

    Moss, W C; Levatin, J L

    2006-08-14

    Despite the intense effort for nearly half a century to construct detailed numerical models of plastic flow and plastic damage accumulation, models for describing fracture, an equally important damage mechanism still cannot describe basic fracture phenomena. Typical fracture models set the stress tensor to zero for tensile fracture and set the deviatoric stress tensor to zero for compressive fracture. One consequence is that the simple case of the tensile fracture of a cylinder under combined compressive radial and tensile axial loads is not modeled correctly. The experimental result is a cylinder that can support compressive radial loads, but no axial load, whereas, the typical numerical result is a cylinder with all stresses equal to zero. This incorrect modeling of fracture locally also has a global effect, because material that is fracturing produces stress release waves, which propagate from the fracture and influence the surrounding material. Consequently, it would be useful to have a model that can describe the stress relief and the resulting anisotropy due to fracture. MOSSFRAC is a material model that simulates three-dimensional tensile and shear fracture in initially isotropic elastic-plastic materials, although its framework is also amenable to initially anisotropic materials. It differs from other models by accounting for the effects of cracks on the constitutive response of the material, so that the previously described experiment, as well as complicated fracture scenarios are simulated more accurately. The model is implemented currently in the LLNL hydrocodes DYNA3D, PARADYN, and ALE3D. The purpose of this technical note is to present a complete qualitative description of the model and quantitative descriptions of salient features.

  9. 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.

  10. 3D Stratigraphic Modeling of Central Aachen

    NASA Astrophysics Data System (ADS)

    Dong, M.; Neukum, C.; Azzam, R.; Hu, H.

    2010-05-01

    Since 1980s, advanced computer hardware and software technologies, as well as multidisciplinary research have provided possibilities to develop advanced three dimensional (3D) simulation software for geosciences application. Some countries, such as USA1) and Canada2) 3), have built up regional 3D geological models based on archival geological data. Such models have played huge roles in engineering geology2), hydrogeology2) 3), geothermal industry1) and so on. In cooperating with the Municipality of Aachen, the Department of Engineering Geology of RWTH Aachen University have built up a computer-based 3D stratigraphic model of 50 meter' depth for the center of Aachen, which is a 5 km by 7 km geologically complex area. The uncorrelated data from multi-resources, discontinuous nature and unconformable connection of the units are main challenges for geological modeling in this area. The reliability of 3D geological models largely depends on the quality and quantity of data. Existing 1D and 2D geological data were collected, including 1) approximately 6970 borehole data of different depth compiled in Microsoft Access database and MapInfo database; 2) a Digital Elevation Model (DEM); 3) geological cross sections; and 4) stratigraphic maps in 1m, 2m and 5m depth. Since acquired data are of variable origins, they were managed step by step. The main processes are described below: 1) Typing errors of borehole data were identified and the corrected data were exported to Variowin2.2 to distinguish duplicate points; 2) The surface elevation of borehole data was compared to the DEM, and differences larger than 3m were eliminated. Moreover, where elevation data missed, it was read from the DEM; 3) Considerable data were collected from municipal constructions, such as residential buildings, factories, and roads. Therefore, many boreholes are spatially clustered, and only one or two representative points were picked out in such areas; After above procedures, 5839 boreholes with -x

  11. 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

  12. SB3D User Manual, Santa Barbara 3D Radiative Transfer Model

    SciTech Connect

    O'Hirok, William

    1999-01-01

    SB3D is a three-dimensional atmospheric and oceanic radiative transfer model for the Solar spectrum. The microphysics employed in the model are the same as used in the model SBDART. It is assumed that the user of SB3D is familiar with SBDART and IDL. SB3D differs from SBDART in that computations are conducted on media in three-dimensions rather than a single column (i.e. plane-parallel), and a stochastic method (Monte Carlo) is employed instead of a numerical approach (Discrete Ordinates) for estimating a solution to the radiative transfer equation. Because of these two differences between SB3D and SBDART, the input and running of SB3D is more unwieldy and requires compromises between model performance and computational expense. Hence, there is no one correct method for running the model and the user must develop a sense to the proper input and configuration of the model.

  13. 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

  14. 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

  15. QSAR Modeling: Where have you been? Where are you going to?

    PubMed Central

    Cherkasov, Artem; Muratov, Eugene N.; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I.; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C.; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E.; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

    2014-01-01

    Quantitative Structure-Activity Relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss: (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists towards collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making. PMID:24351051

  16. QSAR modeling: where have you been? Where are you going to?

    PubMed

    Cherkasov, Artem; Muratov, Eugene N; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

    2014-06-26

    Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making.

  17. QSAR modeling: where have you been? Where are you going to?

    PubMed

    Cherkasov, Artem; Muratov, Eugene N; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

    2014-06-26

    Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making. PMID:24351051

  18. Chemical domain of QSAR models from atom-centered fragments.

    PubMed

    Kühne, Ralph; Ebert, Ralf-Uwe; Schüürmann, Gerrit

    2009-12-01

    A methodology to characterize the chemical domain of qualitative and quantitative structure-activity relationship (QSAR) models based on the atom-centered fragment (ACF) approach is introduced. ACFs decompose the molecule into structural pieces, with each non-hydrogen atom of the molecule acting as an ACF center. ACFs vary with respect to their size in terms of the path length covered in each bonding direction starting from a given central atom and how comprehensively the neighbor atoms (including hydrogen) are described in terms of element type and bonding environment. In addition to these different levels of ACF definitions, the ACF match mode as degree of strictness of the ACF comparison between a test compound and a given ACF pool (such as from a training set) has to be specified. Analyses of the prediction statistics of three QSAR models with their training sets as well as with external test sets and associated subsets demonstrate a clear relationship between the prediction performance and the levels of ACF definition and match mode. The findings suggest that second-order ACFs combined with a borderline match mode may serve as a generic and at the same time a mechanistically sound tool to define and evaluate the chemical domain of QSAR models. Moreover, four standard categories of the ACF-based membership to a given chemical domain (outside, borderline outside, borderline inside, inside) are introduced that provide more specific information about the expected QSAR prediction performance. As such, the ACF-based characterization of the chemical domain appears to be particularly useful for QSAR applications in the context of REACH and other regulatory schemes addressing the safety evaluation of chemical compounds.

  19. 3-D physical models of amitosis (cytokinesis).

    PubMed

    Cheng, Kang; Zou, Changhua

    2005-01-01

    Based on Newton's laws, extended Coulomb's law and published biological data, we develop our 3-D physical models of natural and normal amitosis (cytokinesis), for prokaryotes (bacterial cells) in M phase. We propose following hypotheses: Chromosome rings exclusion: No normally and naturally replicated chromosome rings (RCR) can occupy the same prokaryote, a bacterial cell. The RCR produce spontaneous and strong electromagnetic fields (EMF), that can be alternated environmentally, in protoplasm and cortex. The EMF is approximately a repulsive quasi-static electric (slowly variant and mostly electric) field (EF). The EF forces between the RCR are strong enough, and orderly accumulate contractile proteins that divide the procaryotes in the cell cortex of division plane or directly split the cell compartment envelope longitudinally. The radial component of the EF forces could also make furrows or cleavages of procaryotes. The EF distribution controls the protoplasm partition and completes the amitosis (cytokinesis). After the cytokinesis, the spontaneous and strong EF disappear because the net charge accumulation becomes weak, in the protoplasm. The exclusion is because the two sets of informative objects (RCR) have identical DNA codes information and they are electro magnetically identical, therefore they repulse from each other. We also compare divisions among eukaryotes, prokaryotes, mitochondria and chloroplasts and propose our hypothesis: The principles of our models are applied to divisions of mitochondria and chloroplasts of eucaryotes too because these division mechanisms are closer than others in a view of physics. Though we develop our model using 1 division plane (i.e., 1 cell is divided into 2 cells) as an example, the principle of our model is applied to the cases with multiple division planes (i.e., 1 cell is divided into multiple cells) too.

  20. Mechanism-Based QSAR Modeling of Skin Sensitization.

    PubMed

    Dearden, J C; Hewitt, M; Roberts, D W; Enoch, S J; Rowe, P H; Przybylak, K R; Vaughan-Williams, G D; Smith, M L; Pillai, G G; Katritzky, A R

    2015-10-19

    Many chemicals can induce skin sensitization, and there is a pressing need for non-animal methods to give a quantitative indication of potency. Using two large published data sets of skin sensitizers, we have allocated each sensitizing chemical to one of 10 mechanistic categories and then developed good QSAR models for the seven categories that have a sufficient number of chemicals to allow modeling. Both internal and external validation checks showed that each model had good predictivity.

  1. 3D Models of Stellar Interactions

    NASA Astrophysics Data System (ADS)

    Mohamed, S.; Podsiadlowski, Ph.; Booth, R.; Maercker, M.; Ramstedt, S.; Vlemmings, W.; Harries, T.; Mackey, J.; Langer, N.; Corradi, R.

    2014-04-01

    Symbiotic binaries consist of a cool, evolved mass-losing giant and an accreting compact companion. As symbiotic nebulae show similar morphologies to those in planetary nebulae (so much so that it is often difficult to distinguish between the two), they are ideal laboratories for understanding the role a binary companion plays in shaping the circumstellar envelopes in these evolved systems. We will present 3D Smoothed Particle Hydrodynamics (SPH) models of interacting binaries, e.g. R Aquarii and Mira, and discuss the formation of spiral outflows, arcs, shells and equatorial density enhancements.We will also discuss the implications of the former for planetary nebulae, e.g. the Egg Nebula and Cat's Eye, and the latter for the formation of bipolar geometries, e.g. M2-9. We also investigate accretion and angular momentum evolution in symbiotic binaries which may be important to understand the formation of jets and more episodic mass-loss features we see in circumstellar envelopes and the orbital characteristics of binary central stars of planetary nebulae.

  2. A general method for exploiting QSAR models in lead optimization.

    PubMed

    Lewis, Richard A

    2005-03-10

    Computer-aided drug design tools can generate many useful and powerful models that explain structure-activity relationship (SAR) observations in a quantitative manner. These models can use many different descriptors, functional forms, and methods from simple linear equations through to multilayer neural nets. Using a model, a medicinal chemist can compute an activity, given a structure, but it is much harder to work out what changes are needed to make a structure more active. The impact of a model on the design process would be greatly enhanced if the model were more interpretable to the bench chemist. This paper describes a new protocol for performing automated iterative quantitative structure-activity relationship (QSAR) studies and presents the results of experiments on two QSAR sets from the literature. The fundamental goal of this work is to try to assist the chemist in his search for what to make next.

  3. Multi-view and 3D deformable part models.

    PubMed

    Pepik, Bojan; Stark, Michael; Gehler, Peter; Schiele, Bernt

    2015-11-01

    As objects are inherently 3D, they have been modeled in 3D in the early days of computer vision. Due to the ambiguities arising from mapping 2D features to 3D models, 3D object representations have been neglected and 2D feature-based models are the predominant paradigm in object detection nowadays. While such models have achieved outstanding bounding box detection performance, they come with limited expressiveness, as they are clearly limited in their capability of reasoning about 3D shape or viewpoints. In this work, we bring the worlds of 3D and 2D object representations closer, by building an object detector which leverages the expressive power of 3D object representations while at the same time can be robustly matched to image evidence. To that end, we gradually extend the successful deformable part model [1] to include viewpoint information and part-level 3D geometry information, resulting in several different models with different level of expressiveness. We end up with a 3D object model, consisting of multiple object parts represented in 3D and a continuous appearance model. We experimentally verify that our models, while providing richer object hypotheses than the 2D object models, provide consistently better joint object localization and viewpoint estimation than the state-of-the-art multi-view and 3D object detectors on various benchmarks (KITTI [2] , 3D object classes [3] , Pascal3D+ [4] , Pascal VOC 2007 [5] , EPFL multi-view cars[6] ). PMID:26440264

  4. 3D-GNOME: an integrated web service for structural modeling of the 3D genome.

    PubMed

    Szalaj, Przemyslaw; Michalski, Paul J; Wróblewski, Przemysław; Tang, Zhonghui; Kadlof, Michal; Mazzocco, Giovanni; Ruan, Yijun; Plewczynski, Dariusz

    2016-07-01

    Recent advances in high-throughput chromosome conformation capture (3C) technology, such as Hi-C and ChIA-PET, have demonstrated the importance of 3D genome organization in development, cell differentiation and transcriptional regulation. There is now a widespread need for computational tools to generate and analyze 3D structural models from 3C data. Here we introduce our 3D GeNOme Modeling Engine (3D-GNOME), a web service which generates 3D structures from 3C data and provides tools to visually inspect and annotate the resulting structures, in addition to a variety of statistical plots and heatmaps which characterize the selected genomic region. Users submit a bedpe (paired-end BED format) file containing the locations and strengths of long range contact points, and 3D-GNOME simulates the structure and provides a convenient user interface for further analysis. Alternatively, a user may generate structures using published ChIA-PET data for the GM12878 cell line by simply specifying a genomic region of interest. 3D-GNOME is freely available at http://3dgnome.cent.uw.edu.pl/.

  5. 3D-GNOME: an integrated web service for structural modeling of the 3D genome

    PubMed Central

    Szalaj, Przemyslaw; Michalski, Paul J.; Wróblewski, Przemysław; Tang, Zhonghui; Kadlof, Michal; Mazzocco, Giovanni; Ruan, Yijun; Plewczynski, Dariusz

    2016-01-01

    Recent advances in high-throughput chromosome conformation capture (3C) technology, such as Hi-C and ChIA-PET, have demonstrated the importance of 3D genome organization in development, cell differentiation and transcriptional regulation. There is now a widespread need for computational tools to generate and analyze 3D structural models from 3C data. Here we introduce our 3D GeNOme Modeling Engine (3D-GNOME), a web service which generates 3D structures from 3C data and provides tools to visually inspect and annotate the resulting structures, in addition to a variety of statistical plots and heatmaps which characterize the selected genomic region. Users submit a bedpe (paired-end BED format) file containing the locations and strengths of long range contact points, and 3D-GNOME simulates the structure and provides a convenient user interface for further analysis. Alternatively, a user may generate structures using published ChIA-PET data for the GM12878 cell line by simply specifying a genomic region of interest. 3D-GNOME is freely available at http://3dgnome.cent.uw.edu.pl/. PMID:27185892

  6. QSAR modeling of the inhibition of glycogen synthase kinase-3.

    PubMed

    Katritzky, Alan R; Pacureanu, Liliana M; Dobchev, Dimitar A; Fara, Dan C; Duchowicz, Pablo R; Karelson, Mati

    2006-07-15

    Quantitative structure-activity relationship (QSAR) models of the biological activity (pIC50) of 277 inhibitors of Glycogen Synthase Kinase-3 (GSK-3) are developed using geometrical, topological, quantum mechanical, and electronic descriptors calculated by CODESSA PRO. The linear (multilinear regression) and nonlinear (artificial neural network) models obtained link the structures to their reported activity pIC50. The results are discussed in the light of the main factors that influence the inhibitory activity of the GSK-3 enzyme.

  7. 3D fast wavelet network model-assisted 3D face recognition

    NASA Astrophysics Data System (ADS)

    Said, Salwa; Jemai, Olfa; Zaied, Mourad; Ben Amar, Chokri

    2015-12-01

    In last years, the emergence of 3D shape in face recognition is due to its robustness to pose and illumination changes. These attractive benefits are not all the challenges to achieve satisfactory recognition rate. Other challenges such as facial expressions and computing time of matching algorithms remain to be explored. In this context, we propose our 3D face recognition approach using 3D wavelet networks. Our approach contains two stages: learning stage and recognition stage. For the training we propose a novel algorithm based on 3D fast wavelet transform. From 3D coordinates of the face (x,y,z), we proceed to voxelization to get a 3D volume which will be decomposed by 3D fast wavelet transform and modeled after that with a wavelet network, then their associated weights are considered as vector features to represent each training face . For the recognition stage, an unknown identity face is projected on all the training WN to obtain a new vector features after every projection. A similarity score is computed between the old and the obtained vector features. To show the efficiency of our approach, experimental results were performed on all the FRGC v.2 benchmark.

  8. Anatomy-based 3D skeleton extraction from femur model.

    PubMed

    Gharenazifam, Mina; Arbabi, Ehsan

    2014-11-01

    Using 3D models of bones can highly improve accuracy and reliability of orthopaedic evaluation. However, it may impose excessive computational load. This article proposes a fully automatic method for extracting a compact model of the femur from its 3D model. The proposed method works by extracting a 3D skeleton based on the clinical parameters of the femur. Therefore, in addition to summarizing a 3D model of the bone, the extracted skeleton would preserve important clinical and anatomical information. The proposed method has been applied on 3D models of 10 femurs and the results have been evaluated for different resolutions of data.

  9. Ranking of aquatic toxicity of esters modelled by QSAR.

    PubMed

    Papa, Ester; Battaini, Francesca; Gramatica, Paola

    2005-02-01

    Alternative methods like predictions based on Quantitative Structure-Activity Relationships (QSARs) are now accepted to fill data gaps and define priority lists for more expensive and time consuming assessments. A heterogeneous data set of 74 esters was studied for their aquatic toxicity, and available experimental toxicity data on algae, Daphnia and fish were used to develop statistically validated QSAR models, obtained using multiple linear regression (MLR) by the OLS (Ordinary Least Squares) method and GA-VSS (Variable Subset Selection by Genetic Algorithms) to predict missing values. An ESter Aquatic Toxicity INdex (ESATIN) was then obtained by combining, by PCA, experimental and predicted toxicity data, from which model outliers and esters highly influential due to their structure had been eliminated. Finally this integrated aquatic toxicity index, defined by the PC1 score, was modelled using only a few theoretical molecular descriptors. This last QSAR model, statistically validated for its predictive power, could be proposed as a preliminary evaluative method for screening/prioritising esters according to their integrated aquatic toxicity, just starting from their molecular structure.

  10. (Q)SAR modeling and safety assessment in regulatory review.

    PubMed

    Kruhlak, N L; Benz, R D; Zhou, H; Colatsky, T J

    2012-03-01

    The ability to predict clinical safety based on chemical structures is becoming an increasingly important part of regulatory decision making. (Quantitative) structure-activity relationship ((Q)SAR) models are currently used to evaluate late-arising safety concerns and possible nonclinical effects of a drug and its related compounds when adequate safety data are absent or equivocal. Regulatory use will likely increase with the standardization of analytical approaches, more complete and reliable data collection methods, and a better understanding of toxicity mechanisms.

  11. 3D Modeling Techniques for Print and Digital Media

    NASA Astrophysics Data System (ADS)

    Stephens, Megan Ashley

    In developing my thesis, I looked to gain skills using ZBrush to create 3D models, 3D scanning, and 3D printing. The models created compared the hearts of several vertebrates and were intended for students attending Comparative Vertebrate Anatomy. I used several resources to create a model of the human heart and was able to work from life while creating heart models from other vertebrates. I successfully learned ZBrush and 3D scanning, and successfully printed 3D heart models. ZBrush allowed me to create several intricate models for use in both animation and print media. The 3D scanning technique did not fit my needs for the project, but may be of use for later projects. I was able to 3D print using two different techniques as well.

  12. New QSAR models for polyhalogenated aromatics

    SciTech Connect

    Nevalainen, T.; Kolehmainen, E. . Dept. of Chemistry)

    1994-10-01

    Electronic properties of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polychlorinated diphenyl ethers (PCDEs) were calculated using the semi-empirical AM 1 method. The calculated electronic descriptions--the energy of the lowest unoccupied molecular orbital (E[sub LUMO]), the energy of the highest occupied molecular orbital (E[sub HOMO]), the E[sub LUMO]-E[sub HOMO] gap (dE), and molecular polarizability--are related to the Ah receptor binding affinity values of PCDDs, PCDFs, and PCBs and immunotoxicity values for PCDEs. The quantitative structure-activity relationships (QSARs) based on chlorine substitution patterns were also constructed, and they proved to be very predictive for Ah receptor binding. Significant correlations of the electronic factors were found between the dE and Ah receptor binding affinities for PCDDs, PCDFs, and PCBs and for immunotoxicity of PCDEs. A combination of descriptors E[sub LUMO] and the total number of chlorine atoms attached to a molecule (n[sub Cl]) gives significant correlation for the Ah receptor binding of PCDFs and for immunotoxicity of PCDEs. Hydrophobicity values taken from the literature were shown to be non-significant for toxicity prediction of these polychlorinated compounds.

  13. The 3D rocket combustor acoustics model

    NASA Technical Reports Server (NTRS)

    Priem, Richard J.; Breisacher, Kevin J.

    1992-01-01

    The theory and procedures for determining the characteristics of pressure oscillations in rocket engines with prescribed burning rate oscillations are presented. Analyses including radial and hub baffles and absorbers can be performed in one, two, and three dimensions. Pressure and velocity oscillations calculated using this procedure are presented for the SSME to show the influence of baffles and absorbers on the burning rate oscillations required to achieve neutral stability. Comparisons are made between the results obtained utilizing 1-D, 2-D, and 3-D assumptions with regards to capturing the physical phenomena of interest and computational requirements.

  14. A Historical Excursus on the Statistical Validation Parameters for QSAR Models: A Clarification Concerning Metrics and Terminology.

    PubMed

    Gramatica, Paola; Sangion, Alessandro

    2016-06-27

    In the last years, external validation of QSAR models was the subject of intensive debate in the scientific literature. Different groups have proposed different metrics to find "the best" parameter to characterize the external predictivity of a QSAR model. This editorial summarizes the history of parameter development for the external QSAR model validation and suggests, once again, the concurrent use of several different metrics to assess the real predictive capability of QSAR models.

  15. A Historical Excursus on the Statistical Validation Parameters for QSAR Models: A Clarification Concerning Metrics and Terminology.

    PubMed

    Gramatica, Paola; Sangion, Alessandro

    2016-06-27

    In the last years, external validation of QSAR models was the subject of intensive debate in the scientific literature. Different groups have proposed different metrics to find "the best" parameter to characterize the external predictivity of a QSAR model. This editorial summarizes the history of parameter development for the external QSAR model validation and suggests, once again, the concurrent use of several different metrics to assess the real predictive capability of QSAR models. PMID:27218604

  16. Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis.

    PubMed

    Zhu, Hao; Tropsha, Alexander; Fourches, Denis; Varnek, Alexandre; Papa, Ester; Gramatica, Paola; Oberg, Tomas; Dao, Phuong; Cherkasov, Artem; Tetko, Igor V

    2008-04-01

    Selecting most rigorous quantitative structure-activity relationship (QSAR) approaches is of great importance in the development of robust and predictive models of chemical toxicity. To address this issue in a systematic way, we have formed an international virtual collaboratory consisting of six independent groups with shared interests in computational chemical toxicology. We have compiled an aqueous toxicity data set containing 983 unique compounds tested in the same laboratory over a decade against Tetrahymena pyriformis. A modeling set including 644 compounds was selected randomly from the original set and distributed to all groups that used their own QSAR tools for model development. The remaining 339 compounds in the original set (external set I) as well as 110 additional compounds (external set II) published recently by the same laboratory (after this computational study was already in progress) were used as two independent validation sets to assess the external predictive power of individual models. In total, our virtual collaboratory has developed 15 different types of QSAR models of aquatic toxicity for the training set. The internal prediction accuracy for the modeling set ranged from 0.76 to 0.93 as measured by the leave-one-out cross-validation correlation coefficient ( Q abs2). The prediction accuracy for the external validation sets I and II ranged from 0.71 to 0.85 (linear regression coefficient R absI2) and from 0.38 to 0.83 (linear regression coefficient R absII2), respectively. The use of an applicability domain threshold implemented in most models generally improved the external prediction accuracy but at the same time led to a decrease in chemical space coverage. Finally, several consensus models were developed by averaging the predicted aquatic toxicity for every compound using all 15 models, with or without taking into account their respective applicability domains. We find that consensus models afford higher prediction accuracy for the

  17. 3D Face modeling using the multi-deformable method.

    PubMed

    Hwang, Jinkyu; Yu, Sunjin; Kim, Joongrock; Lee, Sangyoun

    2012-01-01

    In this paper, we focus on the problem of the accuracy performance of 3D face modeling techniques using corresponding features in multiple views, which is quite sensitive to feature extraction errors. To solve the problem, we adopt a statistical model-based 3D face modeling approach in a mirror system consisting of two mirrors and a camera. The overall procedure of our 3D facial modeling method has two primary steps: 3D facial shape estimation using a multiple 3D face deformable model and texture mapping using seamless cloning that is a type of gradient-domain blending. To evaluate our method's performance, we generate 3D faces of 30 individuals and then carry out two tests: accuracy test and robustness test. Our method shows not only highly accurate 3D face shape results when compared with the ground truth, but also robustness to feature extraction errors. Moreover, 3D face rendering results intuitively show that our method is more robust to feature extraction errors than other 3D face modeling methods. An additional contribution of our method is that a wide range of face textures can be acquired by the mirror system. By using this texture map, we generate realistic 3D face for individuals at the end of the paper. PMID:23201976

  18. 3D Face Modeling Using the Multi-Deformable Method

    PubMed Central

    Hwang, Jinkyu; Yu, Sunjin; Kim, Joongrock; Lee, Sangyoun

    2012-01-01

    In this paper, we focus on the problem of the accuracy performance of 3D face modeling techniques using corresponding features in multiple views, which is quite sensitive to feature extraction errors. To solve the problem, we adopt a statistical model-based 3D face modeling approach in a mirror system consisting of two mirrors and a camera. The overall procedure of our 3D facial modeling method has two primary steps: 3D facial shape estimation using a multiple 3D face deformable model and texture mapping using seamless cloning that is a type of gradient-domain blending. To evaluate our method's performance, we generate 3D faces of 30 individuals and then carry out two tests: accuracy test and robustness test. Our method shows not only highly accurate 3D face shape results when compared with the ground truth, but also robustness to feature extraction errors. Moreover, 3D face rendering results intuitively show that our method is more robust to feature extraction errors than other 3D face modeling methods. An additional contribution of our method is that a wide range of face textures can be acquired by the mirror system. By using this texture map, we generate realistic 3D face for individuals at the end of the paper. PMID:23201976

  19. Assessing the RELAPS-3D Heat Conduction Enclosure Model

    SciTech Connect

    McCann, Larry D.

    2008-09-30

    Three heat conduction problems that have exact solutions are modeled with RELAP5-3D using the conduction enclosure model. These comparisons are designed to be used in the RELAP5-3D development assessment scheduled to be completed in 2009. It is shown that with proper input choices and adequate model detail the exact solutions can be matched. In addition, this analysis identified an error and the required correction in the cylindrical and spherical heat conductor models in RELAP5-3D which will be corrected in a future version of RELAP5-3D.

  20. Modelling the effect of structural QSAR parameters on skin penetration using genetic programming

    NASA Astrophysics Data System (ADS)

    Chung, K. K.; Do, D. Q.

    2010-09-01

    In order to model relationships between chemical structures and biological effects in quantitative structure-activity relationship (QSAR) data, an alternative technique of artificial intelligence computing—genetic programming (GP)—was investigated and compared to the traditional method—statistical. GP, with the primary advantage of generating mathematical equations, was employed to model QSAR data and to define the most important molecular descriptions in QSAR data. The models predicted by GP agreed with the statistical results, and the most predictive models of GP were significantly improved when compared to the statistical models using ANOVA. Recently, artificial intelligence techniques have been applied widely to analyse QSAR data. With the capability of generating mathematical equations, GP can be considered as an effective and efficient method for modelling QSAR data.

  1. Comparing a quasi-3D to a full 3D nearshore circulation model: SHORECIRC and ROMS

    USGS Publications Warehouse

    Haas, K.A.; Warner, J.C.

    2009-01-01

    Predictions of nearshore and surf zone processes are important for determining coastal circulation, impacts of storms, navigation, and recreational safety. Numerical modeling of these systems facilitates advancements in our understanding of coastal changes and can provide predictive capabilities for resource managers. There exists many nearshore coastal circulation models, however they are mostly limited or typically only applied as depth integrated models. SHORECIRC is an established surf zone circulation model that is quasi-3D to allow the effect of the variability in the vertical structure of the currents while maintaining the computational advantage of a 2DH model. Here we compare SHORECIRC to ROMS, a fully 3D ocean circulation model which now includes a three dimensional formulation for the wave-driven flows. We compare the models with three different test applications for: (i) spectral waves approaching a plane beach with an oblique angle of incidence; (ii) monochromatic waves driving longshore currents in a laboratory basin; and (iii) monochromatic waves on a barred beach with rip channels in a laboratory basin. Results identify that the models are very similar for the depth integrated flows and qualitatively consistent for the vertically varying components. The differences are primarily the result of the vertically varying radiation stress utilized by ROMS and the utilization of long wave theory for the radiation stress formulation in vertical varying momentum balance by SHORECIRC. The quasi-3D model is faster, however the applicability of the fully 3D model allows it to extend over a broader range of processes, temporal, and spatial scales. ?? 2008 Elsevier Ltd.

  2. a Fast Method for Measuring the Similarity Between 3d Model and 3d Point Cloud

    NASA Astrophysics Data System (ADS)

    Zhang, Zongliang; Li, Jonathan; Li, Xin; Lin, Yangbin; Zhang, Shanxin; Wang, Cheng

    2016-06-01

    This paper proposes a fast method for measuring the partial Similarity between 3D Model and 3D point Cloud (SimMC). It is crucial to measure SimMC for many point cloud-related applications such as 3D object retrieval and inverse procedural modelling. In our proposed method, the surface area of model and the Distance from Model to point Cloud (DistMC) are exploited as measurements to calculate SimMC. Here, DistMC is defined as the weighted distance of the distances between points sampled from model and point cloud. Similarly, Distance from point Cloud to Model (DistCM) is defined as the average distance of the distances between points in point cloud and model. In order to reduce huge computational burdens brought by calculation of DistCM in some traditional methods, we define SimMC as the ratio of weighted surface area of model to DistMC. Compared to those traditional SimMC measuring methods that are only able to measure global similarity, our method is capable of measuring partial similarity by employing distance-weighted strategy. Moreover, our method is able to be faster than other partial similarity assessment methods. We demonstrate the superiority of our method both on synthetic data and laser scanning data.

  3. A 3D Geometry Model Search Engine to Support Learning

    ERIC Educational Resources Information Center

    Tam, Gary K. L.; Lau, Rynson W. H.; Zhao, Jianmin

    2009-01-01

    Due to the popularity of 3D graphics in animation and games, usage of 3D geometry deformable models increases dramatically. Despite their growing importance, these models are difficult and time consuming to build. A distance learning system for the construction of these models could greatly facilitate students to learn and practice at different…

  4. 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

  5. Fringe projection 3D microscopy with the general imaging model.

    PubMed

    Yin, Yongkai; Wang, Meng; Gao, Bruce Z; Liu, Xiaoli; Peng, Xiang

    2015-03-01

    Three-dimensional (3D) imaging and metrology of microstructures is a critical task for the design, fabrication, and inspection of microelements. Newly developed fringe projection 3D microscopy is presented in this paper. The system is configured according to camera-projector layout and long working distance lenses. The Scheimpflug principle is employed to make full use of the limited depth of field. For such a specific system, the general imaging model is introduced to reach a full 3D reconstruction. A dedicated calibration procedure is developed to realize quantitative 3D imaging. Experiments with a prototype demonstrate the accessibility of the proposed configuration, model, and calibration approach.

  6. Complete 3D model reconstruction from multiple views

    NASA Astrophysics Data System (ADS)

    Lin, Huei-Yung; Subbarao, Murali; Park, Soon-Yong

    2002-02-01

    New algorithms are presented for automatically acquiring the complete 3D model of single and multiple objects using rotational stereo. The object is placed on a rotation stage. Stereo images for several viewing directions are taken by rotating the object by known angles. Partial 3D shapes and the corresponding texture maps are obtained using rotational stereo and shape from focus. First, for each view, shape from focus is used to obtain a rough 3D shape and the corresponding focused image. Then, the rough 3D shape and focused images are used in rotational stereo to obtain a more accurate measurement of 3D shape. The rotation axis is calibrated using three fixed points on a planar object and refined during surface integration. The complete 3D model is reconstructed by integrating partial 3D shapes and the corresponding texture maps of the object from multiple views. New algorithms for range image registration, surface integration and texture mapping are presented. Our method can generate 3D models very fast and preserve the texture of objects. A new prototype vision system named Stonybrook VIsion System 2 (SVIS-2) has been built and used in the experiments. In the experiments, 4 viewing directions at 90-degree intervals are used. SVIS-2 can acquire the 3D model of objects within a 250 mm x 250 mm x 250 mm cubic workspace placed about 750 mm from the camera. Both computational algorithms and experimental results on several objects are presented.

  7. GTM-Based QSAR Models and Their Applicability Domains.

    PubMed

    Gaspar, H A; Baskin, I I; Marcou, G; Horvath, D; Varnek, A

    2015-06-01

    In this paper we demonstrate that Generative Topographic Mapping (GTM), a machine learning method traditionally used for data visualisation, can be efficiently applied to QSAR modelling using probability distribution functions (PDF) computed in the latent 2-dimensional space. Several different scenarios of the activity assessment were considered: (i) the "activity landscape" approach based on direct use of PDF, (ii) QSAR models involving GTM-generated on descriptors derived from PDF, and, (iii) the k-Nearest Neighbours approach in 2D latent space. Benchmarking calculations were performed on five different datasets: stability constants of metal cations Ca(2+) , Gd(3+) and Lu(3+) complexes with organic ligands in water, aqueous solubility and activity of thrombin inhibitors. It has been shown that the performance of GTM-based regression models is similar to that obtained with some popular machine-learning methods (random forest, k-NN, M5P regression tree and PLS) and ISIDA fragment descriptors. By comparing GTM activity landscapes built both on predicted and experimental activities, we may visually assess the model's performance and identify the areas in the chemical space corresponding to reliable predictions. The applicability domain used in this work is based on data likelihood. Its application has significantly improved the model performances for 4 out of 5 datasets.

  8. Universal Approach for Structural Interpretation of QSAR/QSPR Models.

    PubMed

    Polishchuk, Pavel G; Kuz'min, Victor E; Artemenko, Anatoly G; Muratov, Eugene N

    2013-10-01

    In this paper we offer a novel approach for the structural interpretation of QSAR models. The major advantage of our developed methodology is its universality, i.e., it can be applied to any QSAR/QSPR model irrespective of chemical descriptors and machine learning methods applied. This universality was achieved by using only the information obtained from substructures of the compounds of interest to interpret model outcomes. Reliability of the offered approach was confirmed by the results of three case studies, including end-points of different types (continuous and binary classification) and nature (solubility, mutagenicity, and inhibition of Transglutaminase 2), various fragment and whole-molecule descriptors (Simplex and Dragon), and multiple modeling techniques (partial least squares, random forest, and support vector machines). We compared the global contributions of molecular fragments obtained using our methodology with known SAR rules derived experimentally. In all cases high concordance between our interpretation and results published by others was observed. Although the proposed interpretation approach could be easily extended to any type of descriptors, we would recommend using Simplex descriptors to achieve a larger variety of investigated molecular fragments. The developed approach is a good tool for interpretation of such "black box" models like random forest, neural networks, etc. Analysis of fragment global contributions and their deviation across a dataset could be useful for the identification of key fragments and structural alerts. This information could be helpful to maximize the positive influence of structural surroundings on the given fragment and to decrease the negative effects. PMID:27480236

  9. GTM-Based QSAR Models and Their Applicability Domains.

    PubMed

    Gaspar, H A; Baskin, I I; Marcou, G; Horvath, D; Varnek, A

    2015-06-01

    In this paper we demonstrate that Generative Topographic Mapping (GTM), a machine learning method traditionally used for data visualisation, can be efficiently applied to QSAR modelling using probability distribution functions (PDF) computed in the latent 2-dimensional space. Several different scenarios of the activity assessment were considered: (i) the "activity landscape" approach based on direct use of PDF, (ii) QSAR models involving GTM-generated on descriptors derived from PDF, and, (iii) the k-Nearest Neighbours approach in 2D latent space. Benchmarking calculations were performed on five different datasets: stability constants of metal cations Ca(2+) , Gd(3+) and Lu(3+) complexes with organic ligands in water, aqueous solubility and activity of thrombin inhibitors. It has been shown that the performance of GTM-based regression models is similar to that obtained with some popular machine-learning methods (random forest, k-NN, M5P regression tree and PLS) and ISIDA fragment descriptors. By comparing GTM activity landscapes built both on predicted and experimental activities, we may visually assess the model's performance and identify the areas in the chemical space corresponding to reliable predictions. The applicability domain used in this work is based on data likelihood. Its application has significantly improved the model performances for 4 out of 5 datasets. PMID:27490381

  10. Universal Approach for Structural Interpretation of QSAR/QSPR Models.

    PubMed

    Polishchuk, Pavel G; Kuz'min, Victor E; Artemenko, Anatoly G; Muratov, Eugene N

    2013-10-01

    In this paper we offer a novel approach for the structural interpretation of QSAR models. The major advantage of our developed methodology is its universality, i.e., it can be applied to any QSAR/QSPR model irrespective of chemical descriptors and machine learning methods applied. This universality was achieved by using only the information obtained from substructures of the compounds of interest to interpret model outcomes. Reliability of the offered approach was confirmed by the results of three case studies, including end-points of different types (continuous and binary classification) and nature (solubility, mutagenicity, and inhibition of Transglutaminase 2), various fragment and whole-molecule descriptors (Simplex and Dragon), and multiple modeling techniques (partial least squares, random forest, and support vector machines). We compared the global contributions of molecular fragments obtained using our methodology with known SAR rules derived experimentally. In all cases high concordance between our interpretation and results published by others was observed. Although the proposed interpretation approach could be easily extended to any type of descriptors, we would recommend using Simplex descriptors to achieve a larger variety of investigated molecular fragments. The developed approach is a good tool for interpretation of such "black box" models like random forest, neural networks, etc. Analysis of fragment global contributions and their deviation across a dataset could be useful for the identification of key fragments and structural alerts. This information could be helpful to maximize the positive influence of structural surroundings on the given fragment and to decrease the negative effects.

  11. An Automated 3d Indoor Topological Navigation Network Modelling

    NASA Astrophysics Data System (ADS)

    Jamali, A.; Rahman, A. A.; Boguslawski, P.; Gold, C. M.

    2015-10-01

    Indoor navigation is important for various applications such as disaster management and safety analysis. In the last decade, indoor environment has been a focus of wide research; that includes developing techniques for acquiring indoor data (e.g. Terrestrial laser scanning), 3D indoor modelling and 3D indoor navigation models. In this paper, an automated 3D topological indoor network generated from inaccurate 3D building models is proposed. In a normal scenario, 3D indoor navigation network derivation needs accurate 3D models with no errors (e.g. gap, intersect) and two cells (e.g. rooms, corridors) should touch each other to build their connections. The presented 3D modeling of indoor navigation network is based on surveying control points and it is less dependent on the 3D geometrical building model. For reducing time and cost of indoor building data acquisition process, Trimble LaserAce 1000 as surveying instrument is used. The modelling results were validated against an accurate geometry of indoor building environment which was acquired using Trimble M3 total station.

  12. Highway 3D model from image and lidar data

    NASA Astrophysics Data System (ADS)

    Chen, Jinfeng; Chu, Henry; Sun, Xiaoduan

    2014-05-01

    We present a new method of highway 3-D model construction developed based on feature extraction in highway images and LIDAR data. We describe the processing road coordinate data that connect the image frames to the coordinates of the elevation data. Image processing methods are used to extract sky, road, and ground regions as well as significant objects (such as signs and building fronts) in the roadside for the 3D model. LIDAR data are interpolated and processed to extract the road lanes as well as other features such as trees, ditches, and elevated objects to form the 3D model. 3D geometry reasoning is used to match the image features to the 3D model. Results from successive frames are integrated to improve the final model.

  13. An Automatic Registration Algorithm for 3D Maxillofacial Model

    NASA Astrophysics Data System (ADS)

    Qiu, Luwen; Zhou, Zhongwei; Guo, Jixiang; Lv, Jiancheng

    2016-09-01

    3D image registration aims at aligning two 3D data sets in a common coordinate system, which has been widely used in computer vision, pattern recognition and computer assisted surgery. One challenging problem in 3D registration is that point-wise correspondences between two point sets are often unknown apriori. In this work, we develop an automatic algorithm for 3D maxillofacial models registration including facial surface model and skull model. Our proposed registration algorithm can achieve a good alignment result between partial and whole maxillofacial model in spite of ambiguous matching, which has a potential application in the oral and maxillofacial reparative and reconstructive surgery. The proposed algorithm includes three steps: (1) 3D-SIFT features extraction and FPFH descriptors construction; (2) feature matching using SAC-IA; (3) coarse rigid alignment and refinement by ICP. Experiments on facial surfaces and mandible skull models demonstrate the efficiency and robustness of our algorithm.

  14. Extending 3D city models with legal information

    NASA Astrophysics Data System (ADS)

    Frank, A. U.; Fuhrmann, T.; Navratil, G.

    2012-10-01

    3D city models represent existing physical objects and their topological and functional relations. In everyday life the rights and responsibilities connected to these objects, primarily legally defined rights and obligations but also other socially and culturally established rights, are of importance. The rights and obligations are defined in various laws and it is often difficult to identify the rules applicable for a certain case. The existing 2D cadastres show civil law rights and obligations and plans to extend them to provide information about public law restrictions for land use are in several countries under way. It is tempting to design extensions to the 3D city models to provide information about legal rights in 3D. The paper analyses the different types of information that are needed to reduce conflicts and to facilitate decisions about land use. We identify the role 3D city models augmented with planning information in 3D can play, but do not advocate a general conversion from 2D to 3D for the legal cadastre. Space is not anisotropic and the up/down dimension is practically very different from the two dimensional plane - this difference must be respected when designing spatial information systems. The conclusions are: (1) continue the current regime for ownership of apartments, which is not ownership of a 3D volume, but co-ownership of a building with exclusive use of some rooms; such exclusive use rights could be shown in a 3D city model; (2) ownership of 3D volumes for complex and unusual building situations can be reported in a 3D city model, but are not required everywhere; (3) indicate restrictions for land use and building in 3D city models, with links to the legal sources.

  15. RELAP5-3D Compressor Model

    SciTech Connect

    James E. Fisher; Cliff B. Davis; Walter L. Weaver

    2005-06-01

    A compressor model has been implemented in the RELAP5-3D© code. The model is similar to that of the existing pump model, and performs the same function on a gas as the pump performs on a single-phase or two-phase fluid. The compressor component consists of an inlet junction and a control volume, and optionally, an outlet junction. This feature permits cascading compressor components in series. The equations describing the physics of the compressor are derived from first principles. These equations are used to obtain the head, the torque, and the energy dissipation. Compressor performance is specified using a map, specific to the design of the machine, in terms of the ratio of outlet-to-inlet total (or stagnation) pressure and adiabatic efficiency as functions of rotational velocity and flow rate. The input quantities are specified in terms of dimensionless variables, which are corrected to stagnation density and stagnation sound speed. A small correction was formulated for the input of efficiency to account for the error introduced by assumption of constant density when integrating the momentum equation. Comparison of the results of steady-state operation of the compressor model to those of the MIT design calculation showed excellent agreement for both pressure ratio and power.

  16. A 3D model of Pluto's atmosphere

    NASA Astrophysics Data System (ADS)

    Vangvichith, M.; Forget, F.; Wordsworth, R.

    2011-10-01

    For the first time, we have built a GCM of Pluto's atmosphere, adapted from the model of Triton's, recently developed[9] . In fact, Pluto and Triton have a lot of similarities (atmospheric, orbital). This GCM will allow to better understand the complex mechanism of the planet and to study the variation of the thermal profile during time.

  17. Beyond 3D culture models of cancer

    PubMed Central

    Tanner, Kandice; Gottesman, Michael M.

    2016-01-01

    The mechanisms underlying the spatiotemporal evolution of tumor ecosystems present a challenge in evaluating drug efficacy. In this Perspective, we address the use of three-dimensional in vitro culture models to delineate the dynamic interplay between the tumor and the host microenvironment in an effort to attain realistic platforms for assessing pharmaceutical efficacy in patients. PMID:25877888

  18. Venusian Applications of 3D Convection Modeling

    NASA Technical Reports Server (NTRS)

    Bonaccorso, Timary Annie

    2011-01-01

    This study models mantle convection on Venus using the 'cubed sphere' code OEDIPUS, which models one-sixth of the planet in spherical geometry. We are attempting to balance internal heating, bottom mantle viscosity, and temperature difference across Venus' mantle, in order to create a realistic model that matches with current planetary observations. We also have begun to run both lower and upper mantle simulations to determine whether layered (as opposed to whole-mantle) convection might produce more efficient heat transfer, as well as to model coronae formation in the upper mantle. Upper mantle simulations are completed using OEDIPUS' Cartesian counterpart, JOCASTA. This summer's central question has been how to define a mantle plume. Traditionally, we have defined a hot plume the region with temperature at or above 40% of the difference between the maximum and horizontally averaged temperature, and a cold plume as the region with 40% of the difference between the minimum and average temperature. For less viscous cases (1020 Pa?s), the plumes generated by that definition lacked vigor, displaying buoyancies 1/100th of those found in previous, higher viscosity simulations (1021 Pa?s). As the mantle plumes with large buoyancy flux are most likely to produce topographic uplift and volcanism, the low viscosity cases' plumes may not produce observable deformation. In an effort to eliminate the smallest plumes, we experimented with different lower bound parameters and temperature percentages.

  19. Virtual 3d City Modeling: Techniques and Applications

    NASA Astrophysics Data System (ADS)

    Singh, S. P.; Jain, K.; Mandla, V. R.

    2013-08-01

    3D city model is a digital representation of the Earth's surface and it's related objects such as Building, Tree, Vegetation, and some manmade feature belonging to urban area. There are various terms used for 3D city models such as "Cybertown", "Cybercity", "Virtual City", or "Digital City". 3D city models are basically a computerized or digital model of a city contains the graphic representation of buildings and other objects in 2.5 or 3D. Generally three main Geomatics approach are using for Virtual 3-D City models generation, in first approach, researcher are using Conventional techniques such as Vector Map data, DEM, Aerial images, second approach are based on High resolution satellite images with LASER scanning, In third method, many researcher are using Terrestrial images by using Close Range Photogrammetry with DSM & Texture mapping. We start this paper from the introduction of various Geomatics techniques for 3D City modeling. These techniques divided in to two main categories: one is based on Automation (Automatic, Semi-automatic and Manual methods), and another is Based on Data input techniques (one is Photogrammetry, another is Laser Techniques). After details study of this, finally in short, we are trying to give the conclusions of this study. In the last, we are trying to give the conclusions of this research paper and also giving a short view for justification and analysis, and present trend for 3D City modeling. This paper gives an overview about the Techniques related with "Generation of Virtual 3-D City models using Geomatics Techniques" and the Applications of Virtual 3D City models. Photogrammetry, (Close range, Aerial, Satellite), Lasergrammetry, GPS, or combination of these modern Geomatics techniques play a major role to create a virtual 3-D City model. Each and every techniques and method has some advantages and some drawbacks. Point cloud model is a modern trend for virtual 3-D city model. Photo-realistic, Scalable, Geo-referenced virtual 3

  20. Image based 3D city modeling : Comparative study

    NASA Astrophysics Data System (ADS)

    Singh, S. P.; Jain, K.; Mandla, V. R.

    2014-06-01

    3D city model is a digital representation of the Earth's surface and it's related objects such as building, tree, vegetation, and some manmade feature belonging to urban area. The demand of 3D city modeling is increasing rapidly for various engineering and non-engineering applications. Generally four main image based approaches were used for virtual 3D city models generation. In first approach, researchers were used Sketch based modeling, second method is Procedural grammar based modeling, third approach is Close range photogrammetry based modeling and fourth approach is mainly based on Computer Vision techniques. SketchUp, CityEngine, Photomodeler and Agisoft Photoscan are the main softwares to represent these approaches respectively. These softwares have different approaches & methods suitable for image based 3D city modeling. Literature study shows that till date, there is no complete such type of comparative study available to create complete 3D city model by using images. This paper gives a comparative assessment of these four image based 3D modeling approaches. This comparative study is mainly based on data acquisition methods, data processing techniques and output 3D model products. For this research work, study area is the campus of civil engineering department, Indian Institute of Technology, Roorkee (India). This 3D campus acts as a prototype for city. This study also explains various governing parameters, factors and work experiences. This research work also gives a brief introduction, strengths and weakness of these four image based techniques. Some personal comment is also given as what can do or what can't do from these softwares. At the last, this study shows; it concluded that, each and every software has some advantages and limitations. Choice of software depends on user requirements of 3D project. For normal visualization project, SketchUp software is a good option. For 3D documentation record, Photomodeler gives good result. For Large city

  1. NoSQL Based 3D City Model Management System

    NASA Astrophysics Data System (ADS)

    Mao, B.; Harrie, L.; Cao, J.; Wu, Z.; Shen, J.

    2014-04-01

    To manage increasingly complicated 3D city models, a framework based on NoSQL database is proposed in this paper. The framework supports import and export of 3D city model according to international standards such as CityGML, KML/COLLADA and X3D. We also suggest and implement 3D model analysis and visualization in the framework. For city model analysis, 3D geometry data and semantic information (such as name, height, area, price and so on) are stored and processed separately. We use a Map-Reduce method to deal with the 3D geometry data since it is more complex, while the semantic analysis is mainly based on database query operation. For visualization, a multiple 3D city representation structure CityTree is implemented within the framework to support dynamic LODs based on user viewpoint. Also, the proposed framework is easily extensible and supports geoindexes to speed up the querying. Our experimental results show that the proposed 3D city management system can efficiently fulfil the analysis and visualization requirements.

  2. Modelling Polymer Deformation during 3D Printing

    NASA Astrophysics Data System (ADS)

    McIlroy, Claire; Olmsted, Peter

    Three-dimensional printing has the potential to transform manufacturing processes, yet improving the strength of printed parts, to equal that of traditionally-manufactured parts, remains an underlying issue. The fused deposition modelling technique involves melting a thermoplastic, followed by layer-by-layer extrusion to fabricate an object. The key to ensuring strength at the weld between layers is successful inter-diffusion. However, prior to welding, both the extrusion process and the cooling temperature profile can significantly deform the polymer micro-structure and, consequently, how well the polymers are able to ``re-entangle'' across the weld. In particular, polymer alignment in the flow can cause de-bonding of the layers and create defects. We have developed a simple model of the non-isothermal extrusion process to explore the effects that typical printing conditions and material rheology have on the conformation of a polymer melt. In particular, we incorporate both stretch and orientation using the Rolie-Poly constitutive equation to examine the melt structure as it flows through the nozzle, the subsequent alignment with the build plate and the resulting deformation due to the fixed nozzle height, which is typically less than the nozzle radius.

  3. Modeling 3D facial shape from DNA.

    PubMed

    Claes, Peter; Liberton, Denise K; Daniels, Katleen; Rosana, Kerri Matthes; Quillen, Ellen E; Pearson, Laurel N; McEvoy, Brian; Bauchet, Marc; Zaidi, Arslan A; Yao, Wei; Tang, Hua; Barsh, Gregory S; Absher, Devin M; Puts, David A; Rocha, Jorge; Beleza, Sandra; Pereira, Rinaldo W; Baynam, Gareth; Suetens, Paul; Vandermeulen, Dirk; Wagner, Jennifer K; Boster, James S; Shriver, Mark D

    2014-03-01

    Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes. The facial effects of these variables are summarized as response-based imputed predictor (RIP) variables, which are validated using self-reported sex, genomic ancestry, and observer-based facial ratings (femininity and proportional ancestry) and judgments (sex and population group). By jointly modeling sex, genomic ancestry, and genotype, the independent effects of particular alleles on facial features can be uncovered. Results on a set of 20 genes showing significant effects on facial features provide support for this approach as a novel means to identify genes affecting normal-range facial features and for approximating the appearance of a face from genetic markers. PMID:24651127

  4. Modeling 3D Facial Shape from DNA

    PubMed Central

    Claes, Peter; Liberton, Denise K.; Daniels, Katleen; Rosana, Kerri Matthes; Quillen, Ellen E.; Pearson, Laurel N.; McEvoy, Brian; Bauchet, Marc; Zaidi, Arslan A.; Yao, Wei; Tang, Hua; Barsh, Gregory S.; Absher, Devin M.; Puts, David A.; Rocha, Jorge; Beleza, Sandra; Pereira, Rinaldo W.; Baynam, Gareth; Suetens, Paul; Vandermeulen, Dirk; Wagner, Jennifer K.; Boster, James S.; Shriver, Mark D.

    2014-01-01

    Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes. The facial effects of these variables are summarized as response-based imputed predictor (RIP) variables, which are validated using self-reported sex, genomic ancestry, and observer-based facial ratings (femininity and proportional ancestry) and judgments (sex and population group). By jointly modeling sex, genomic ancestry, and genotype, the independent effects of particular alleles on facial features can be uncovered. Results on a set of 20 genes showing significant effects on facial features provide support for this approach as a novel means to identify genes affecting normal-range facial features and for approximating the appearance of a face from genetic markers. PMID:24651127

  5. 3D PIC Modeling of Microcavity Discharge

    NASA Astrophysics Data System (ADS)

    Hopkins, Matthew; Manginell, Ronald; Moore, Christopher; Yee, Benjamin; Moorman, Matthew

    2015-09-01

    We present a number of techniques and challenges in simulating the transient behavior of a microcavity discharge. Our microcavities are typically cylindrical with diameters approximately 50 - 100 μm, heights of 50 - 200 μm, pressure near atmospheric, and operate at a few hundred volts. We employ a fully kinetic simulation methodology, the Particle-in-Cell (PIC) method, with interparticle collisions handled via methods based on direct simulation Monte Carlo (DSMC). In particular, we explicitly include kinetic electrons. Some of the challenges we encounter include variations in number densities, external circuit coupling, and time step resolution constraints. By employing dynamic particle weighting (particle weights vary over time by species and location) we can mitigate some of the challenges modeling systems with 107 variations in number densities. Smoothing mechanisms have been used to attempt to mitigate external circuit response. We perform our simulations on hundreds or thousands of processing cores to accommodate the computational work inherent in using relatively small time step sizes (e.g., 50 fs for a 100 ns calculation). In addition, particle weighting issues inherent to three-dimensional low temperature plasma systems will be mentioned. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE-AC04-94AL85000.

  6. Probabilistic Modeling of Conformational Space for 3D Machine Learning Approaches.

    PubMed

    Jahn, Andreas; Hinselmann, Georg; Fechner, Nikolas; Henneges, Carsten; Zell, Andreas

    2010-05-17

    We present a new probabilistic encoding of the conformational space of a molecule that allows for the integration into common similarity calculations. The method uses distance profiles of flexible atom-pairs and computes generative models that describe the distance distribution in the conformational space. The generative models permit the use of probabilistic kernel functions and, therefore, our approach can be used to extend existing 3D molecular kernel functions, as applied in support vector machines, to build QSAR models. The resulting kernels are valid 4D kernel functions and reduce the dependency of the model quality on suitable conformations of the molecules. We showed in several experiments the robust performance of the 4D kernel function, which was extended by our approach, in comparison to the original 3D-based kernel function. The new method compares the conformational space of two molecules within one kernel evaluation. Hence, the number of kernel evaluations is significantly reduced in comparison to common kernel-based conformational space averaging techniques. Additionally, the performance gain of the extended model correlates with the flexibility of the data set and enables an a priori estimation of the model improvement.

  7. Enzymes/non-enzymes classification model complexity based on composition, sequence, 3D and topological indices.

    PubMed

    Munteanu, Cristian Robert; González-Díaz, Humberto; Magalhães, Alexandre L

    2008-09-21

    The huge amount of new proteins that need a fast enzymatic activity characterization creates demands of protein QSAR theoretical models. The protein parameters that can be used for an enzyme/non-enzyme classification includes the simpler indices such as composition, sequence and connectivity, also called topological indices (TIs) and the computationally expensive 3D descriptors. A comparison of the 3D versus lower dimension indices has not been reported with respect to the power of discrimination of proteins according to enzyme action. A set of 966 proteins (enzymes and non-enzymes) whose structural characteristics are provided by PDB/DSSP files was analyzed with Python/Biopython scripts, STATISTICA and Weka. The list of indices includes, but it is not restricted to pure composition indices (residue fractions), DSSP secondary structure protein composition and 3D indices (surface and access). We also used mixed indices such as composition-sequence indices (Chou's pseudo-amino acid compositions or coupling numbers), 3D-composition (surface fractions) and DSSP secondary structure amino acid composition/propensities (obtained with our Prot-2S Web tool). In addition, we extend and test for the first time several classic TIs for the Randic's protein sequence Star graphs using our Sequence to Star Graph (S2SG) Python application. All the indices were processed with general discriminant analysis models (GDA), neural networks (NN) and machine learning (ML) methods and the results are presented versus complexity, average of Shannon's information entropy (Sh) and data/method type. This study compares for the first time all these classes of indices to assess the ratios between model accuracy and indices/model complexity in enzyme/non-enzyme discrimination. The use of different methods and complexity of data shows that one cannot establish a direct relation between the complexity and the accuracy of the model. PMID:18606172

  8. Predicting Error Bars for QSAR Models

    SciTech Connect

    Schroeter, Timon; Mika, Sebastian; Ter Laak, Antonius; Suelzle, Detlev; Ganzer, Ursula; Heinrich, Nikolaus; Mueller, Klaus-Robert

    2007-09-18

    Unfavorable physicochemical properties often cause drug failures. It is therefore important to take lipophilicity and water solubility into account early on in lead discovery. This study presents log D{sub 7} models built using Gaussian Process regression, Support Vector Machines, decision trees and ridge regression algorithms based on 14556 drug discovery compounds of Bayer Schering Pharma. A blind test was conducted using 7013 new measurements from the last months. We also present independent evaluations using public data. Apart from accuracy, we discuss the quality of error bars that can be computed by Gaussian Process models, and ensemble and distance based techniques for the other modelling approaches.

  9. Predicting Error Bars for QSAR Models

    NASA Astrophysics Data System (ADS)

    Schroeter, Timon; Schwaighofer, Anton; Mika, Sebastian; Ter Laak, Antonius; Suelzle, Detlev; Ganzer, Ursula; Heinrich, Nikolaus; Müller, Klaus-Robert

    2007-09-01

    Unfavorable physicochemical properties often cause drug failures. It is therefore important to take lipophilicity and water solubility into account early on in lead discovery. This study presents log D7 models built using Gaussian Process regression, Support Vector Machines, decision trees and ridge regression algorithms based on 14556 drug discovery compounds of Bayer Schering Pharma. A blind test was conducted using 7013 new measurements from the last months. We also present independent evaluations using public data. Apart from accuracy, we discuss the quality of error bars that can be computed by Gaussian Process models, and ensemble and distance based techniques for the other modelling approaches.

  10. 3D-model building of the jaw impression

    NASA Astrophysics Data System (ADS)

    Ahmed, Moumen T.; Yamany, Sameh M.; Hemayed, Elsayed E.; Farag, Aly A.

    1997-03-01

    A novel approach is proposed to obtain a record of the patient's occlusion using computer vision. Data acquisition is obtained using intra-oral video cameras. The technique utilizes shape from shading to extract 3D information from 2D views of the jaw, and a novel technique for 3D data registration using genetic algorithms. The resulting 3D model can be used for diagnosis, treatment planning, and implant purposes. The overall purpose of this research is to develop a model-based vision system for orthodontics to replace traditional approaches. This system will be flexible, accurate, and will reduce the cost of orthodontic treatments.

  11. 3D model-based still image object categorization

    NASA Astrophysics Data System (ADS)

    Petre, Raluca-Diana; Zaharia, Titus

    2011-09-01

    This paper proposes a novel recognition scheme algorithm for semantic labeling of 2D object present in still images. The principle consists of matching unknown 2D objects with categorized 3D models in order to infer the semantics of the 3D object to the image. We tested our new recognition framework by using the MPEG-7 and Princeton 3D model databases in order to label unknown images randomly selected from the web. Results obtained show promising performances, with recognition rate up to 84%, which opens interesting perspectives in terms of semantic metadata extraction from still images/videos.

  12. Summary on Several Key Techniques in 3D Geological Modeling

    PubMed Central

    2014-01-01

    Several key techniques in 3D geological modeling including planar mesh generation, spatial interpolation, and surface intersection are summarized in this paper. Note that these techniques are generic and widely used in various applications but play a key role in 3D geological modeling. There are two essential procedures in 3D geological modeling: the first is the simulation of geological interfaces using geometric surfaces and the second is the building of geological objects by means of various geometric computations such as the intersection of surfaces. Discrete geometric surfaces that represent geological interfaces can be generated by creating planar meshes first and then spatially interpolating; those surfaces intersect and then form volumes that represent three-dimensional geological objects such as rock bodies. In this paper, the most commonly used algorithms of the key techniques in 3D geological modeling are summarized. PMID:24772029

  13. Quantification of the accuracy of MRI generated 3D models of long bones compared to CT generated 3D models.

    PubMed

    Rathnayaka, Kanchana; Momot, Konstantin I; Noser, Hansrudi; Volp, Andrew; Schuetz, Michael A; Sahama, Tony; Schmutz, Beat

    2012-04-01

    Orthopaedic fracture fixation implants are increasingly being designed using accurate 3D models of long bones based on computer tomography (CT). Unlike CT, magnetic resonance imaging (MRI) does not involve ionising radiation and is therefore a desirable alternative to CT. This study aims to quantify the accuracy of MRI-based 3D models compared to CT-based 3D models of long bones. The femora of five intact cadaver ovine limbs were scanned using a 1.5 T MRI and a CT scanner. Image segmentation of CT and MRI data was performed using a multi-threshold segmentation method. Reference models were generated by digitising the bone surfaces free of soft tissue with a mechanical contact scanner. The MRI- and CT-derived models were validated against the reference models. The results demonstrated that the CT-based models contained an average error of 0.15 mm while the MRI-based models contained an average error of 0.23 mm. Statistical validation shows that there are no significant differences between 3D models based on CT and MRI data. These results indicate that the geometric accuracy of MRI based 3D models was comparable to that of CT-based models and therefore MRI is a potential alternative to CT for generation of 3D models with high geometric accuracy.

  14. Formal representation of 3D structural geological models

    NASA Astrophysics Data System (ADS)

    Wang, Zhangang; Qu, Honggang; Wu, Zixing; Yang, Hongjun; Du, Qunle

    2016-05-01

    The development and widespread application of geological modeling methods has increased demands for the integration and sharing services of three dimensional (3D) geological data. However, theoretical research in the field of geological information sciences is limited despite the widespread use of Geographic Information Systems (GIS) in geology. In particular, fundamental research on the formal representations and standardized spatial descriptions of 3D structural models is required. This is necessary for accurate understanding and further applications of geological data in 3D space. In this paper, we propose a formal representation method for 3D structural models using the theory of point set topology, which produces a mathematical definition for the major types of geological objects. The spatial relationships between geologic boundaries, structures, and units are explained in detail using the 9-intersection model. Reasonable conditions for describing the topological space of 3D structural models are also provided. The results from this study can be used as potential support for the standardized representation and spatial quality evaluation of 3D structural models, as well as for specific needs related to model-based management, query, and analysis.

  15. Performance Evaluation of 3d Modeling Software for Uav Photogrammetry

    NASA Astrophysics Data System (ADS)

    Yanagi, H.; Chikatsu, H.

    2016-06-01

    UAV (Unmanned Aerial Vehicle) photogrammetry, which combines UAV and freely available internet-based 3D modeling software, is widely used as a low-cost and user-friendly photogrammetry technique in the fields such as remote sensing and geosciences. In UAV photogrammetry, only the platform used in conventional aerial photogrammetry is changed. Consequently, 3D modeling software contributes significantly to its expansion. However, the algorithms of the 3D modelling software are black box algorithms. As a result, only a few studies have been able to evaluate their accuracy using 3D coordinate check points. With this motive, Smart3DCapture and Pix4Dmapper were downloaded from the Internet and commercial software PhotoScan was also employed; investigations were performed in this paper using check points and images obtained from UAV.

  16. QSAR Modeling and Prediction of Drug-Drug Interactions.

    PubMed

    Zakharov, Alexey V; Varlamova, Ekaterina V; Lagunin, Alexey A; Dmitriev, Alexander V; Muratov, Eugene N; Fourches, Denis; Kuz'min, Victor E; Poroikov, Vladimir V; Tropsha, Alexander; Nicklaus, Marc C

    2016-02-01

    Severe adverse drug reactions (ADRs) are the fourth leading cause of fatality in the U.S. with more than 100,000 deaths per year. As up to 30% of all ADRs are believed to be caused by drug-drug interactions (DDIs), typically mediated by cytochrome P450s, possibilities to predict DDIs from existing knowledge are important. We collected data from public sources on 1485, 2628, 4371, and 27,966 possible DDIs mediated by four cytochrome P450 isoforms 1A2, 2C9, 2D6, and 3A4 for 55, 73, 94, and 237 drugs, respectively. For each of these data sets, we developed and validated QSAR models for the prediction of DDIs. As a unique feature of our approach, the interacting drug pairs were represented as binary chemical mixtures in a 1:1 ratio. We used two types of chemical descriptors: quantitative neighborhoods of atoms (QNA) and simplex descriptors. Radial basis functions with self-consistent regression (RBF-SCR) and random forest (RF) were utilized to build QSAR models predicting the likelihood of DDIs for any pair of drug molecules. Our models showed balanced accuracy of 72-79% for the external test sets with a coverage of 81.36-100% when a conservative threshold for the model's applicability domain was applied. We generated virtually all possible binary combinations of marketed drugs and employed our models to identify drug pairs predicted to be instances of DDI. More than 4500 of these predicted DDIs that were not found in our training sets were confirmed by data from the DrugBank database. PMID:26669717

  17. Automatic Texture Mapping of Architectural and Archaeological 3d Models

    NASA Astrophysics Data System (ADS)

    Kersten, T. P.; Stallmann, D.

    2012-07-01

    Today, detailed, complete and exact 3D models with photo-realistic textures are increasingly demanded for numerous applications in architecture and archaeology. Manual texture mapping of 3D models by digital photographs with software packages, such as Maxon Cinema 4D, Autodesk 3Ds Max or Maya, still requires a complex and time-consuming workflow. So, procedures for automatic texture mapping of 3D models are in demand. In this paper two automatic procedures are presented. The first procedure generates 3D surface models with textures by web services, while the second procedure textures already existing 3D models with the software tmapper. The program tmapper is based on the Multi Layer 3D image (ML3DImage) algorithm and developed in the programming language C++. The studies showing that the visibility analysis using the ML3DImage algorithm is not sufficient to obtain acceptable results of automatic texture mapping. To overcome the visibility problem the Point Cloud Painter algorithm in combination with the Z-buffer-procedure will be applied in the future.

  18. QSAR and pharmacophore modeling of natural and synthetic antimalarial prodiginines.

    PubMed

    Singh, Baljinder; Vishwakarma, Ram A; Bharate, Sandip B

    2013-09-01

    Prodiginines are a family of linear and cyclic oligopyrrole red-pigmented compounds possessing antibacterial, anticancer and immunosuppressive activities and are produced by actinomycetes and other eubacteria. Recently, prodiginines have been reported to possess potent in vitro as well as in vivo antimalarial activity against chloroquine sensitive D6 and multi-drug resistant Dd2 strains of Plasmodium falciparum. In the present paper, a QSAR and pharmacophore modeling for a series of natural and synthetic prodiginines was performed to find out structural features which are crucial for antimalarial activity against these D6 and Dd2 Plasmodium strains. The study indicated that inertia moment 2 length, Kier Chi6 (path) index, kappa 3 index and Wiener topological index plays important role in antimalarial activity against D6 strain whereas descriptors inertia moment 2 length, ADME H-bond donors, VAMP polarization XX component and VAMP quadpole XZ component play important role in antimalarial activity against Dd2 strain. Furthermore, a five-point pharmacophore (ADHRR) model with one H-bond acceptor (A), one H-bond donor (D), one hydrophobic group (H) and two aromatic rings (R) as pharmacophore features was developed for D6 strain by PHASE module of Schrodinger suite. Similarly a six-point pharmacophore AADDRR was developed for Dd2 strain activity. All developed QSAR models showed good correlation coefficient (r² > 0.7), higher F value (F >20) and excellent predictive power (Q² > 0.6). Developed models will be highly useful for predicting antimalarial activity of new compounds and could help in designing better molecules with enhanced antimalarial activity. Furthermore, calculated ADME properties indicated drug-likeness of prodiginines.

  19. Gis-Based Smart Cartography Using 3d Modeling

    NASA Astrophysics Data System (ADS)

    Malinverni, E. S.; Tassetti, A. N.

    2013-08-01

    3D City Models have evolved to be important tools for urban decision processes and information systems, especially in planning, simulation, analysis, documentation and heritage management. On the other hand existing and in use numerical cartography is often not suitable to be used in GIS because not geometrically and topologically correctly structured. The research aim is to 3D structure and organize a numeric cartography for GIS and turn it into CityGML standardized features. The work is framed around a first phase of methodological analysis aimed to underline which existing standard (like ISO and OGC rules) can be used to improve the quality requirement of a cartographic structure. Subsequently, from this technical specifics, it has been investigated the translation in formal contents, using an owner interchange software (SketchUp), to support some guide lines implementations to generate a GIS3D structured in GML3. It has been therefore predisposed a test three-dimensional numerical cartography (scale 1:500, generated from range data captured by 3D laser scanner), tested on its quality according to the previous standard and edited when and where necessary. Cad files and shapefiles are converted into a final 3D model (Google SketchUp model) and then exported into a 3D city model (CityGML LoD1/LoD2). The GIS3D structure has been managed in a GIS environment to run further spatial analysis and energy performance estimate, not achievable in a 2D environment. In particular geometrical building parameters (footprint, volume etc.) are computed and building envelop thermal characteristics are derived from. Lastly, a simulation is carried out to deal with asbestos and home renovating charges and show how the built 3D city model can support municipal managers with risk diagnosis of the present situation and development of strategies for a sustainable redevelop.

  20. Development of quantitative structure activity relationship (QSAR) model for disinfection byproduct (DBP) research: A review of methods and resources.

    PubMed

    Chen, Baiyang; Zhang, Tian; Bond, Tom; Gan, Yiqun

    2015-12-15

    Quantitative structure-activity relationship (QSAR) models are tools for linking chemical activities with molecular structures and compositions. Due to the concern about the proliferating number of disinfection byproducts (DBPs) in water and the associated financial and technical burden, researchers have recently begun to develop QSAR models to investigate the toxicity, formation, property, and removal of DBPs. However, there are no standard procedures or best practices regarding how to develop QSAR models, which potentially limit their wide acceptance. In order to facilitate more frequent use of QSAR models in future DBP research, this article reviews the processes required for QSAR model development, summarizes recent trends in QSAR-DBP studies, and shares some important resources for QSAR development (e.g., free databases and QSAR programs). The paper follows the four steps of QSAR model development, i.e., data collection, descriptor filtration, algorithm selection, and model validation; and finishes by highlighting several research needs. Because QSAR models may have an important role in progressing our understanding of DBP issues, it is hoped that this paper will encourage their future use for this application.

  1. Implementation of virtual models from sheet metal forming simulation into physical 3D colour models using 3D printing

    NASA Astrophysics Data System (ADS)

    Junk, S.

    2016-08-01

    Today the methods of numerical simulation of sheet metal forming offer a great diversity of possibilities for optimization in product development and in process design. However, the results from simulation are only available as virtual models. Because there are any forming tools available during the early stages of product development, physical models that could serve to represent the virtual results are therefore lacking. Physical 3D-models can be created using 3D-printing and serve as an illustration and present a better understanding of the simulation results. In this way, the results from the simulation can be made more “comprehensible” within a development team. This paper presents the possibilities of 3D-colour printing with particular consideration of the requirements regarding the implementation of sheet metal forming simulation. Using concrete examples of sheet metal forming, the manufacturing of 3D colour models will be expounded upon on the basis of simulation results.

  2. 5D-QSAR for spirocyclic sigma1 receptor ligands by Quasar receptor surface modeling.

    PubMed

    Oberdorf, Christoph; Schmidt, Thomas J; Wünsch, Bernhard

    2010-07-01

    Based on a contiguous and structurally as well as biologically diverse set of 87 sigma(1) ligands, a 5D-QSAR study was conducted in which a quasi-atomistic receptor surface modeling approach (program package Quasar) was applied. The superposition of the ligands was performed with the tool Pharmacophore Elucidation (MOE-package), which takes all conformations of the ligands into account. This procedure led to four pharmacophoric structural elements with aromatic, hydrophobic, cationic and H-bond acceptor properties. Using the aligned structures a 3D-model of the ligand binding site of the sigma(1) receptor was obtained, whose general features are in good agreement with previous assumptions on the receptor structure, but revealed some novel insights since it represents the receptor surface in more detail. Thus, e.g., our model indicates the presence of an H-bond acceptor moiety in the binding site as counterpart to the ligands' cationic ammonium center, rather than a negatively charged carboxylate group. The presented QSAR model is statistically valid and represents the biological data of all tested compounds, including a test set of 21 ligands not used in the modeling process, with very good to excellent accuracy [q(2) (training set, n=66; leave 1/3 out) = 0.84, p(2) (test set, n=21)=0.64]. Moreover, the binding affinities of 13 further spirocyclic sigma(1) ligands were predicted with reasonable accuracy (mean deviation in pK(i) approximately 0.8). Thus, in addition to novel insights into the requirements for binding of spirocyclic piperidines to the sigma(1) receptor, the presented model can be used successfully in the rational design of new sigma(1) ligands.

  3. 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

  4. Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

    EPA Science Inventory

    This pyrethroid insecticide parameter review is an extension of our interest in developing quantitative structure–activity relationship–physiologically based pharmacokinetic/pharmacodynamic (QSAR-PBPK/PD) models for assessing health risks, which interest started with the organoph...

  5. Cholesteryl ester transfer protein inhibitors in coronary heart disease: Validated comparative QSAR modeling of N, N-disubstituted trifluoro-3-amino-2-propanols.

    PubMed

    Mondal, Chanchal; Halder, Amit Kumar; Adhikari, Nilanjan; Jha, Tarun

    2013-10-01

    Cholesteryl ester transfer protein (CETP) converts high density lipoprotein cholesterol to low density lipoproteins. It is a promising target for treatment of coronary heart disease. Two dimensional quantitative structure activity relationship (2D-QSAR), hologram QSAR (HQSAR) studies and comparative molecular field analysis (CoMFA) as well as comparative molecular similarity analysis (CoMSIA) were performed on 104 CETP inhibitors. The statistical qualities of generated models were justified by internal and external validation, i.e., q(2) and R(2)pred respectively. The best 2D-QSAR model was obtained with q(2) and R(2)pred values of 0.794 and 0.796 respectively. The 2D-QSAR study suggests that unsaturation, branching and van der Waals volumes may play important roles. The HQSAR model showed q(2) and R(2)pred values of 0.628 and 0.550 respectively. Similarly, CoMFA model showed q(2) and R(2)pred values of 0.707 and 0.755 respectively whereas CoMSIA model was obtained with q(2) and R(2)pred values of 0.696 and 0.703 respectively. CoMFA and CoMSIA studies indicate that steric factors are important at substituted phenoxy and tetrafluoroethoxy groups whereas electropositive factors play important role at difluoromethyl group. The results of 3D-QSAR studies validate those of 2D-QSAR and HQSAR studies as well as the earlier observed SAR data. Current work may help to develop better CETP inhibitors.

  6. Multivariate 3D modelling of Scottish soil properties

    NASA Astrophysics Data System (ADS)

    Poggio, Laura; Gimona, Alessandro

    2015-04-01

    Information regarding soil properties across landscapes at national or continental scales is critical for better soil and environmental management and for climate regulation and adaptation policy. The prediction of soil properties variation in space and time and their uncertainty is an important part of environmental modelling. Soil properties, and in particular the 3 fractions of soil texture, exhibit strong co-variation among themselves and therefore taking into account this correlation leads to spatially more accurate results. In this study the continuous vertical and lateral distributions of relevant soil properties in Scottish soils were modelled with a multivariate 3D-GAM+GS approach. The approach used involves 1) modelling the multivariate trend with full 3D spatial correlation, i.e., exploiting the values of the neighbouring pixels in 3D-space, and 2) 3D kriging to interpolate the residuals. The values at each cell for each of the considered depth layers were defined using a hybrid GAM-geostatistical 3D model, combining the fitting of a GAM (generalised Additive Models) to estimate multivariate trend of the variables, using a 3D smoother with related covariates. Gaussian simulations of the model residuals were used as spatial component to account for local details. A dataset of about 26,000 horizons (7,800 profiles) was used for this study. A validation set was randomly selected as 25% of the full dataset. Numerous covariates derived from globally available data, such as MODIS and SRTM, are considered. The results of the 3D-GAM+kriging showed low RMSE values, good R squared and an accurate reproduction of the spatial structure of the data for a range of soil properties. The results have an out-of-sample RMSE between 10 to 15% of the observed range when taking into account the whole profile. The approach followed allows the assessment of the uncertainty of both the trend and the residuals.

  7. Shape: A 3D Modeling Tool for Astrophysics.

    PubMed

    Steffen, Wolfgang; Koning, Nicholas; Wenger, Stephan; Morisset, Christophe; Magnor, Marcus

    2011-04-01

    We present a flexible interactive 3D morpho-kinematical modeling application for astrophysics. Compared to other systems, our application reduces the restrictions on the physical assumptions, data type, and amount that is required for a reconstruction of an object's morphology. It is one of the first publicly available tools to apply interactive graphics to astrophysical modeling. The tool allows astrophysicists to provide a priori knowledge about the object by interactively defining 3D structural elements. By direct comparison of model prediction with observational data, model parameters can then be automatically optimized to fit the observation. The tool has already been successfully used in a number of astrophysical research projects.

  8. 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.

  9. Modeling 3-D Effects in the DIII-D Boundary

    NASA Astrophysics Data System (ADS)

    Evans, T. E.; Moyer, R. A.; Reiter, D.; Kasilov, S. V.; Runov, A. M.

    2002-11-01

    Resonant magnetic perturbations δ br from the DIII-D locked and resistive wall mode control coils (C-coil and I-coil, respectively) affect ne and Te profiles in both the pedestal and core. To understand why these δ br perturbations change the plasma profiles we first model the edge magnetic topology with a field line integration code, TRIP3D code. In general, the TRIP3D results indicate that the control coils create stochastic layers with as much as 25% edge magnetic flux connected to the divertors and walls. While heat and particle transport modeling in open stochastic layers is inherently very difficult, Monte Carlo methods appear to provide the most reasonable approach with which to address these issues. As such, we have assessed the possibility of coupling a recently developed Monte Carlo heat transport code, the E3D code, [A.M. Runov et al., Phys. Plasmas 8, 916 (2001)] to TRIP3D. We will discuss how this coupling can best be accomplished and what must be done to benchmark the TRIP3D/E3D ensemble using DIII-D experimental data. We will also discuss the analysis of proposed designs for a dedicated DIII-D stochastic boundary layer coil which produce minimal δ br core perturbations.

  10. 3D MI-DRAGON: new model for the reconstruction of US FDA drug- target network and theoretical-experimental studies of inhibitors of rasagiline derivatives for AChE.

    PubMed

    Prado-Prado, Francisco; García-Mera, Xerardo; Escobar, Manuel; Alonso, Nerea; Caamaño, Olga; Yañez, Matilde; González-Díaz, Humberto

    2012-01-01

    The number of neurodegenerative diseases has been increasing in recent years. Many of the drug candidates to be used in the treatment of neurodegenerative diseases present specific 3D structural features. An important protein in this sense is the acetylcholinesterase (AChE), which is the target of many Alzheimer's dementia drugs. Consequently, the prediction of Drug-Protein Interactions (DPIs/nDPIs) between new drug candidates and specific 3D structure and targets is of major importance. To this end, we can use Quantitative Structure-Activity Relationships (QSAR) models to carry out a rational DPIs prediction. Unfortunately, many previous QSAR models developed to predict DPIs take into consideration only 2D structural information and codify the activity against only one target. To solve this problem we can develop some 3D multi-target QSAR (3D mt-QSAR) models. In this study, using the 3D MI-DRAGON technique, we have introduced a new predictor for DPIs based on two different well-known software. We have used the MARCH-INSIDE (MI) and DRAGON software to calculate 3D structural parameters for drugs and targets respectively. Both classes of 3D parameters were used as input to train Artificial Neuronal Network (ANN) algorithms using as benchmark dataset the complex network (CN) made up of all DPIs between US FDA approved drugs and their targets. The entire dataset was downloaded from the DrugBank database. The best 3D mt-QSAR predictor found was an ANN of Multi-Layer Perceptron-type (MLP) with profile MLP 37:37-24-1:1. This MLP classifies correctly 274 out of 321 DPIs (Sensitivity = 85.35%) and 1041 out of 1190 nDPIs (Specificity = 87.48%), corresponding to training Accuracy = 87.03%. We have validated the model with external predicting series with Sensitivity = 84.16% (542/644 DPIs; Specificity = 87.51% (2039/2330 nDPIs) and Accuracy = 86.78%. The new CNs of DPIs reconstructed from US FDA can be used to explore large DPI databases in order to discover both new drugs

  11. Improving 3d Spatial Queries Search: Newfangled Technique of Space Filling Curves in 3d City Modeling

    NASA Astrophysics Data System (ADS)

    Uznir, U.; Anton, F.; Suhaibah, A.; Rahman, A. A.; Mioc, D.

    2013-09-01

    The advantages of three dimensional (3D) city models can be seen in various applications including photogrammetry, urban and regional planning, computer games, etc.. They expand the visualization and analysis capabilities of Geographic Information Systems on cities, and they can be developed using web standards. However, these 3D city models consume much more storage compared to two dimensional (2D) spatial data. They involve extra geometrical and topological information together with semantic data. Without a proper spatial data clustering method and its corresponding spatial data access method, retrieving portions of and especially searching these 3D city models, will not be done optimally. Even though current developments are based on an open data model allotted by the Open Geospatial Consortium (OGC) called CityGML, its XML-based structure makes it challenging to cluster the 3D urban objects. In this research, we propose an opponent data constellation technique of space-filling curves (3D Hilbert curves) for 3D city model data representation. Unlike previous methods, that try to project 3D or n-dimensional data down to 2D or 3D using Principal Component Analysis (PCA) or Hilbert mappings, in this research, we extend the Hilbert space-filling curve to one higher dimension for 3D city model data implementations. The query performance was tested using a CityGML dataset of 1,000 building blocks and the results are presented in this paper. The advantages of implementing space-filling curves in 3D city modeling will improve data retrieval time by means of optimized 3D adjacency, nearest neighbor information and 3D indexing. The Hilbert mapping, which maps a subinterval of the [0, 1] interval to the corresponding portion of the d-dimensional Hilbert's curve, preserves the Lebesgue measure and is Lipschitz continuous. Depending on the applications, several alternatives are possible in order to cluster spatial data together in the third dimension compared to its

  12. Aortic valve and ascending aortic root modeling from 3D and 3D+t CT

    NASA Astrophysics Data System (ADS)

    Grbic, Saša; Ionasec, Razvan I.; Zäuner, Dominik; Zheng, Yefeng; Georgescu, Bogdan; Comaniciu, Dorin

    2010-02-01

    Aortic valve disorders are the most frequent form of valvular heart disorders (VHD) affecting nearly 3% of the global population. A large fraction among them are aortic root diseases, such as aortic root aneurysm, often requiring surgical procedures (valve-sparing) as a treatment. Visual non-invasive assessment techniques could assist during pre-selection of adequate patients, planning procedures and afterward evaluation of the same. However state of the art approaches try to model a rather short part of the aortic root, insufficient to assist the physician during intervention planning. In this paper we propose a novel approach for morphological and functional quantification of both the aortic valve and the ascending aortic root. A novel physiological shape model is introduced, consisting of the aortic valve root, leaflets and the ascending aortic root. The model parameters are hierarchically estimated using robust and fast learning-based methods. Experiments performed on 63 CT sequences (630 Volumes) and 20 single phase CT volumes demonstrated an accuracy of 1.45mm and an performance of 30 seconds (3D+t) for this approach. To the best of our knowledge this is the first time a complete model of the aortic valve (including leaflets) and the ascending aortic root, estimated from CT, has been proposed.

  13. STELLOPT Modeling of the 3D Diagnostic Response in ITER

    SciTech Connect

    Lazerson, Samuel A

    2013-05-07

    The ITER three dimensional diagnostic response to an n=3 resonant magnetic perturbation is modeled using the STELLOPT code. The in-vessel coils apply a resonant magnetic perturbation (RMP) fi eld which generates a 4 cm edge displacement from axisymmetry as modeled by the VMEC 3D equilibrium code. Forward modeling of flux loop and magnetic probe response with the DIAGNO code indicates up to 20 % changes in measured plasma signals. Simulated LIDAR measurements of electron temperature indicate 2 cm shifts on the low field side of the plasma. This suggests that the ITER diagnostic will be able to diagnose the 3D structure of the equilibria.

  14. Potential of 3D City Models to assess flood vulnerability

    NASA Astrophysics Data System (ADS)

    Schröter, Kai; Bochow, Mathias; Schüttig, Martin; Nagel, Claus; Ross, Lutz; Kreibich, Heidi

    2016-04-01

    Vulnerability, as the product of exposure and susceptibility, is a key factor of the flood risk equation. Furthermore, the estimation of flood loss is very sensitive to the choice of the vulnerability model. Still, in contrast to elaborate hazard simulations, vulnerability is often considered in a simplified manner concerning the spatial resolution and geo-location of exposed objects as well as the susceptibility of these objects at risk. Usually, area specific potential flood loss is quantified on the level of aggregated land-use classes, and both hazard intensity and resistance characteristics of affected objects are represented in highly simplified terms. We investigate the potential of 3D City Models and spatial features derived from remote sensing data to improve the differentiation of vulnerability in flood risk assessment. 3D City Models are based on CityGML, an application scheme of the Geography Markup Language (GML), which represents the 3D geometry, 3D topology, semantics and appearance of objects on different levels of detail. As such, 3D City Models offer detailed spatial information which is useful to describe the exposure and to characterize the susceptibility of residential buildings at risk. This information is further consolidated with spatial features of the building stock derived from remote sensing data. Using this database a spatially detailed flood vulnerability model is developed by means of data-mining. Empirical flood damage data are used to derive and to validate flood susceptibility models for individual objects. We present first results from a prototype application in the city of Dresden, Germany. The vulnerability modeling based on 3D City Models and remote sensing data is compared i) to the generally accepted good engineering practice based on area specific loss potential and ii) to a highly detailed representation of flood vulnerability based on a building typology using urban structure types. Comparisons are drawn in terms of

  15. 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.

  16. Thermal 3D modeling system based on 3-view geometry

    NASA Astrophysics Data System (ADS)

    Yu, Sunjin; Kim, Joongrock; Lee, Sangyoun

    2012-11-01

    In this paper, we propose a novel thermal three-dimensional (3D) modeling system that includes 3D shape, visual, and thermal infrared information and solves a registration problem among these three types of information. The proposed system consists of a projector, a visual camera and, a thermal camera (PVT). To generate 3D shape information, we use a structured light technique, which consists of a visual camera and a projector. A thermal camera is added to the structured light system in order to provide thermal information. To solve the correspondence problem between the three sensors, we use three-view geometry. Finally, we obtain registered PVT data, which includes visual, thermal, and 3D shape information. Among various potential applications such as industrial measurements, biological experiments, military usage, and so on, we have adapted the proposed method to biometrics, particularly for face recognition. With the proposed method, we obtain multi-modal 3D face data that includes not only textural information but also data regarding head pose, 3D shape, and thermal information. Experimental results show that the performance of the proposed face recognition system is not limited by head pose variation which is a serious problem in face recognition.

  17. 3D MHD Models of Active Region Loops

    NASA Technical Reports Server (NTRS)

    Ofman, Leon

    2004-01-01

    Present imaging and spectroscopic observations of active region loops allow to determine many physical parameters of the coronal loops, such as the density, temperature, velocity of flows in loops, and the magnetic field. However, due to projection effects many of these parameters remain ambiguous. Three dimensional imaging in EUV by the STEREO spacecraft will help to resolve the projection ambiguities, and the observations could be used to setup 3D MHD models of active region loops to study the dynamics and stability of active regions. Here the results of 3D MHD models of active region loops are presented, and the progress towards more realistic 3D MHD models of active regions. In particular the effects of impulsive events on the excitation of active region loop oscillations, and the generation, propagations and reflection of EIT waves are shown. It is shown how 3D MHD models together with 3D EUV observations can be used as a diagnostic tool for active region loop physical parameters, and to advance the science of the sources of solar coronal activity.

  18. Quality of 3D Models Generated by SFM Technology

    NASA Astrophysics Data System (ADS)

    Marčiš, Marián

    2013-12-01

    Using various types of automation in digital photogrammetry is associated with questions such as the accuracy of a 3D model generated on various types of surfaces and textures, the financial costs of the equipment needed, and also the time costs of the processing. This topic deals with the actual technology of computer vision, which allows the automated exterior orientation of images, camera calibration, and the generation of 3D models directly from images of the object itself, based on the automatic detection of significant points. Detailed testing is done using the Agisoft PhotoScan system, and the camera configuration is solved with respect to the accuracy of the 3D model generated and the time consumption of the calculations for the different types of textures and the different settings for the processing.

  19. 3D model of amphioxus steroid receptor complexed with estradiol

    SciTech Connect

    Baker, Michael E.; Chang, David J.

    2009-08-28

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  20. 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.

  1. Geospatial Modelling Approach for 3d Urban Densification Developments

    NASA Astrophysics Data System (ADS)

    Koziatek, O.; Dragićević, S.; Li, S.

    2016-06-01

    With growing populations, economic pressures, and the need for sustainable practices, many urban regions are rapidly densifying developments in the vertical built dimension with mid- and high-rise buildings. The location of these buildings can be projected based on key factors that are attractive to urban planners, developers, and potential buyers. Current research in this area includes various modelling approaches, such as cellular automata and agent-based modelling, but the results are mostly linked to raster grids as the smallest spatial units that operate in two spatial dimensions. Therefore, the objective of this research is to develop a geospatial model that operates on irregular spatial tessellations to model mid- and high-rise buildings in three spatial dimensions (3D). The proposed model is based on the integration of GIS, fuzzy multi-criteria evaluation (MCE), and 3D GIS-based procedural modelling. Part of the City of Surrey, within the Metro Vancouver Region, Canada, has been used to present the simulations of the generated 3D building objects. The proposed 3D modelling approach was developed using ESRI's CityEngine software and the Computer Generated Architecture (CGA) language.

  2. Parallel Optimization of 3D Cardiac Electrophysiological Model Using GPU

    PubMed Central

    Xia, Yong; Wang, Kuanquan; Zhang, Henggui

    2015-01-01

    Large-scale 3D virtual heart model simulations are highly demanding in computational resources. This imposes a big challenge to the traditional computation resources based on CPU environment, which already cannot meet the requirement of the whole computation demands or are not easily available due to expensive costs. GPU as a parallel computing environment therefore provides an alternative to solve the large-scale computational problems of whole heart modeling. In this study, using a 3D sheep atrial model as a test bed, we developed a GPU-based simulation algorithm to simulate the conduction of electrical excitation waves in the 3D atria. In the GPU algorithm, a multicellular tissue model was split into two components: one is the single cell model (ordinary differential equation) and the other is the diffusion term of the monodomain model (partial differential equation). Such a decoupling enabled realization of the GPU parallel algorithm. Furthermore, several optimization strategies were proposed based on the features of the virtual heart model, which enabled a 200-fold speedup as compared to a CPU implementation. In conclusion, an optimized GPU algorithm has been developed that provides an economic and powerful platform for 3D whole heart simulations. PMID:26581957

  3. Robust model-based 3d/3D fusion using sparse matching for minimally invasive surgery.

    PubMed

    Neumann, Dominik; Grbic, Sasa; John, Matthias; Navab, Nassir; Hornegger, Joachim; Ionasec, Razvan

    2013-01-01

    Classical surgery is being disrupted by minimally invasive and transcatheter procedures. As there is no direct view or access to the affected anatomy, advanced imaging techniques such as 3D C-arm CT and C-arm fluoroscopy are routinely used for intra-operative guidance. However, intra-operative modalities have limited image quality of the soft tissue and a reliable assessment of the cardiac anatomy can only be made by injecting contrast agent, which is harmful to the patient and requires complex acquisition protocols. We propose a novel sparse matching approach for fusing high quality pre-operative CT and non-contrasted, non-gated intra-operative C-arm CT by utilizing robust machine learning and numerical optimization techniques. Thus, high-quality patient-specific models can be extracted from the pre-operative CT and mapped to the intra-operative imaging environment to guide minimally invasive procedures. Extensive quantitative experiments demonstrate that our model-based fusion approach has an average execution time of 2.9 s, while the accuracy lies within expert user confidence intervals. PMID:24505663

  4. Ligand Biological Activity Predictions Using Fingerprint-Based Artificial Neural Networks (FANN-QSAR)

    PubMed Central

    Myint, Kyaw Z.; Xie, Xiang-Qun

    2015-01-01

    This chapter focuses on the fingerprint-based artificial neural networks QSAR (FANN-QSAR) approach to predict biological activities of structurally diverse compounds. Three types of fingerprints, namely ECFP6, FP2, and MACCS, were used as inputs to train the FANN-QSAR models. The results were benchmarked against known 2D and 3D QSAR methods, and the derived models were used to predict cannabinoid (CB) ligand binding activities as a case study. In addition, the FANN-QSAR model was used as a virtual screening tool to search a large NCI compound database for lead cannabinoid compounds. We discovered several compounds with good CB2 binding affinities ranging from 6.70 nM to 3.75 μM. The studies proved that the FANN-QSAR method is a useful approach to predict bioactivities or properties of ligands and to find novel lead compounds for drug discovery research. PMID:25502380

  5. 3D Model Generation From the Engineering Drawing

    NASA Astrophysics Data System (ADS)

    Vaský, Jozef; Eliáš, Michal; Bezák, Pavol; Červeňanská, Zuzana; Izakovič, Ladislav

    2010-01-01

    The contribution deals with the transformation of engineering drawings in a paper form into a 3D computer representation. A 3D computer model can be further processed in CAD/CAM system, it can be modified, archived, and a technical drawing can be then generated from it as well. The transformation process from paper form to the data one is a complex and difficult one, particularly owing to the different types of drawings, forms of displayed objects and encountered errors and deviations from technical standards. The algorithm for 3D model generating from an orthogonal vector input representing a simplified technical drawing of the rotational part is described in this contribution. The algorithm was experimentally implemented as ObjectARX application in the AutoCAD system and the test sample as the representation of the rotational part was used for verificaton.

  6. Space Partitioning for Privacy Enabled 3D City Models

    NASA Astrophysics Data System (ADS)

    Filippovska, Y.; Wichmann, A.; Kada, M.

    2016-10-01

    Due to recent technological progress, data capturing and processing of highly detailed (3D) data has become extensive. And despite all prospects of potential uses, data that includes personal living spaces and public buildings can also be considered as a serious intrusion into people's privacy and a threat to security. It becomes especially critical if data is visible by the general public. Thus, a compromise is needed between open access to data and privacy requirements which can be very different for each application. As privacy is a complex and versatile topic, the focus of this work particularly lies on the visualization of 3D urban data sets. For the purpose of privacy enabled visualizations of 3D city models, we propose to partition the (living) spaces into privacy regions, each featuring its own level of anonymity. Within each region, the depicted 2D and 3D geometry and imagery is anonymized with cartographic generalization techniques. The underlying spatial partitioning is realized as a 2D map generated as a straight skeleton of the open space between buildings. The resulting privacy cells are then merged according to the privacy requirements associated with each building to form larger regions, their borderlines smoothed, and transition zones established between privacy regions to have a harmonious visual appearance. It is exemplarily demonstrated how the proposed method generates privacy enabled 3D city models.

  7. 3D shape decomposition and comparison for gallbladder modeling

    NASA Astrophysics Data System (ADS)

    Huang, Weimin; Zhou, Jiayin; Liu, Jiang; Zhang, Jing; Yang, Tao; Su, Yi; Law, Gim Han; Chui, Chee Kong; Chang, Stephen

    2011-03-01

    This paper presents an approach to gallbladder shape comparison by using 3D shape modeling and decomposition. The gallbladder models can be used for shape anomaly analysis and model comparison and selection in image guided robotic surgical training, especially for laparoscopic cholecystectomy simulation. The 3D shape of a gallbladder is first represented as a surface model, reconstructed from the contours segmented in CT data by a scheme of propagation based voxel learning and classification. To better extract the shape feature, the surface mesh is further down-sampled by a decimation filter and smoothed by a Taubin algorithm, followed by applying an advancing front algorithm to further enhance the regularity of the mesh. Multi-scale curvatures are then computed on the regularized mesh for the robust saliency landmark localization on the surface. The shape decomposition is proposed based on the saliency landmarks and the concavity, measured by the distance from the surface point to the convex hull. With a given tolerance the 3D shape can be decomposed and represented as 3D ellipsoids, which reveal the shape topology and anomaly of a gallbladder. The features based on the decomposed shape model are proposed for gallbladder shape comparison, which can be used for new model selection. We have collected 19 sets of abdominal CT scan data with gallbladders, some shown in normal shape and some in abnormal shapes. The experiments have shown that the decomposed shapes reveal important topology features.

  8. Geodiversity: Exploration of 3D geological model space

    NASA Astrophysics Data System (ADS)

    Lindsay, M. D.; Jessell, M. W.; Ailleres, L.; Perrouty, S.; de Kemp, E.; Betts, P. G.

    2013-05-01

    The process of building a 3D model necessitates the reconciliation of field observations, geophysical interpretation, geological data uncertainty and the prevailing tectonic evolution hypotheses and interpretations. Uncertainty is compounded when clustered data points collected at local scales are statistically upscaled to one or two points for use in regional models. Interpretation is required to interpolate between sparse field data points using ambiguous geophysical data in covered terranes. It becomes clear that multiple interpretations are possible during model construction. The various interpretations are considered as potential natural representatives, but pragmatism typically dictates that just a single interpretation is offered by the modelling process. Uncertainties are introduced into the 3D model during construction from a variety of sources and through data set optimisation that produces a single model. Practices such as these are likely to result in a model that does not adequately represent the target geology. A set of geometrical ‘geodiversity’ metrics are used to analyse a 3D model of the Gippsland Basin, southeastern Australia after perturbing geological input data via uncertainty simulation. The resulting sets of perturbed geological observations are used to calculate a suite of geological 3D models that display a range of geological architectures. The concept of biodiversity has been adapted for the geosciences to quantify geometric variability, or geodiversity, between models in order to understand the effect uncertainty has models geometry. Various geometrical relationships (depth, volume, contact surface area, curvature and geological complexity) are used to describe the range of possibilities exhibited throughout the model suite. End-member models geodiversity metrics are classified in a similar manner to taxonomic descriptions. Further analysis of the model suite is performed using principal component analysis (PCA) to determine

  9. Improving Semantic Updating Method on 3d City Models Using Hybrid Semantic-Geometric 3d Segmentation Technique

    NASA Astrophysics Data System (ADS)

    Sharkawi, K.-H.; Abdul-Rahman, A.

    2013-09-01

    Cities and urban areas entities such as building structures are becoming more complex as the modern human civilizations continue to evolve. The ability to plan and manage every territory especially the urban areas is very important to every government in the world. Planning and managing cities and urban areas based on printed maps and 2D data are getting insufficient and inefficient to cope with the complexity of the new developments in big cities. The emergence of 3D city models have boosted the efficiency in analysing and managing urban areas as the 3D data are proven to represent the real world object more accurately. It has since been adopted as the new trend in buildings and urban management and planning applications. Nowadays, many countries around the world have been generating virtual 3D representation of their major cities. The growing interest in improving the usability of 3D city models has resulted in the development of various tools for analysis based on the 3D city models. Today, 3D city models are generated for various purposes such as for tourism, location-based services, disaster management and urban planning. Meanwhile, modelling 3D objects are getting easier with the emergence of the user-friendly tools for 3D modelling available in the market. Generating 3D buildings with high accuracy also has become easier with the availability of airborne Lidar and terrestrial laser scanning equipments. The availability and accessibility to this technology makes it more sensible to analyse buildings in urban areas using 3D data as it accurately represent the real world objects. The Open Geospatial Consortium (OGC) has accepted CityGML specifications as one of the international standards for representing and exchanging spatial data, making it easier to visualize, store and manage 3D city models data efficiently. CityGML able to represents the semantics, geometry, topology and appearance of 3D city models in five well-defined Level-of-Details (LoD), namely LoD0

  10. Multispecies QSAR modeling for predicting the aquatic toxicity of diverse organic chemicals for regulatory toxicology.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Kumar, Anuj; Mohan, Dinesh

    2014-05-19

    The research aims to develop multispecies quantitative structure-activity relationships (QSARs) modeling tools capable of predicting the acute toxicity of diverse chemicals in various Organization for Economic Co-operation and Development (OECD) recommended test species of different trophic levels for regulatory toxicology. Accordingly, the ensemble learning (EL) approach based classification and regression QSAR models, such as decision treeboost (DTB) and decision tree forest (DTF) implementing stochastic gradient boosting and bagging algorithms were developed using the algae (P. subcapitata) experimental toxicity data for chemicals. The EL-QSAR models were successfully applied to predict toxicities of wide groups of chemicals in other test species including algae (S. obliguue), daphnia, fish, and bacteria. Structural diversity of the selected chemicals and those of the end-point toxicity data of five different test species were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W) statistics. Predictive and generalization abilities of the constructed QSAR models were compared using statistical parameters. The developed QSAR models (DTB and DTF) yielded a considerably high classification accuracy in complete data of model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26% and 92.14%-94.12% in four test species, respectively, whereas regression QSAR models (DTB and DTF) rendered high correlation (R(2)) between the measured and model predicted toxicity end-point values and low mean-squared error in model building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and 0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species. The developed QSAR models exhibited good predictive and generalization abilities in different test species of varied trophic levels and can be used for predicting the toxicities of new chemicals for screening and prioritization of chemicals for regulation.

  11. Multispecies QSAR modeling for predicting the aquatic toxicity of diverse organic chemicals for regulatory toxicology.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Kumar, Anuj; Mohan, Dinesh

    2014-05-19

    The research aims to develop multispecies quantitative structure-activity relationships (QSARs) modeling tools capable of predicting the acute toxicity of diverse chemicals in various Organization for Economic Co-operation and Development (OECD) recommended test species of different trophic levels for regulatory toxicology. Accordingly, the ensemble learning (EL) approach based classification and regression QSAR models, such as decision treeboost (DTB) and decision tree forest (DTF) implementing stochastic gradient boosting and bagging algorithms were developed using the algae (P. subcapitata) experimental toxicity data for chemicals. The EL-QSAR models were successfully applied to predict toxicities of wide groups of chemicals in other test species including algae (S. obliguue), daphnia, fish, and bacteria. Structural diversity of the selected chemicals and those of the end-point toxicity data of five different test species were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W) statistics. Predictive and generalization abilities of the constructed QSAR models were compared using statistical parameters. The developed QSAR models (DTB and DTF) yielded a considerably high classification accuracy in complete data of model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26% and 92.14%-94.12% in four test species, respectively, whereas regression QSAR models (DTB and DTF) rendered high correlation (R(2)) between the measured and model predicted toxicity end-point values and low mean-squared error in model building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and 0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species. The developed QSAR models exhibited good predictive and generalization abilities in different test species of varied trophic levels and can be used for predicting the toxicities of new chemicals for screening and prioritization of chemicals for regulation. PMID:24738471

  12. Enhanced LOD Concepts for Virtual 3d City Models

    NASA Astrophysics Data System (ADS)

    Benner, J.; Geiger, A.; Gröger, G.; Häfele, K.-H.; Löwner, M.-O.

    2013-09-01

    Virtual 3D city models contain digital three dimensional representations of city objects like buildings, streets or technical infrastructure. Because size and complexity of these models continuously grow, a Level of Detail (LoD) concept effectively supporting the partitioning of a complete model into alternative models of different complexity and providing metadata, addressing informational content, complexity and quality of each alternative model is indispensable. After a short overview on various LoD concepts, this paper discusses the existing LoD concept of the CityGML standard for 3D city models and identifies a number of deficits. Based on this analysis, an alternative concept is developed and illustrated with several examples. It differentiates between first, a Geometric Level of Detail (GLoD) and a Semantic Level of Detail (SLoD), and second between the interior building and its exterior shell. Finally, a possible implementation of the new concept is demonstrated by means of an UML model.

  13. Teaching the geological subsurface with 3D models

    NASA Astrophysics Data System (ADS)

    Thorpe, Steve; Ward, Emma

    2014-05-01

    3D geological models have great potential as a resource when teaching geological concepts as it allows the student to visualise and interrogate UK geology. They are especially useful when dealing with the conversion of 2D field, map and GIS outputs into three dimensional geological units, which is a common problem for many students. Today's earth science students use a variety of skills and processes during their learning experience including spatial thinking, image construction, detecting patterns, making predictions and deducing the orientation of themselves. 3D geological models can reinforce spatial thinking strategies and encourage students to think about processes and properties, in turn helping the student to recognise pre-learnt geological principles in the field and to convert what they see at the surface into a picture of what is going on at depth. The British Geological Survey (BGS) has been producing digital 3D geological models for over 10 years. The models produced are revolutionising the working practices, data standards and products of the BGS. Sharing our geoscience information with academia is highlighted throughout the BGS strategy as is instilling practical skills in future geoscience professionals, such as model building and interpretation. In 2009 a project was launched to investigate the potential of the models as a teaching resource. The study included justifying if and how the models help students to learn, how models have been used historically, and how other forms of modelling are being used today. BGS now produce 3D geological models for use by anyone teaching or learning geoscience. They incorporate educational strategies that will develop geospatial skills and alleviate potential problems that some students experience. They are contained within contemporary case studies and show standard geological concepts, structures, sedimentary rocks, cross sections and field techniques. 3D geological models of the Isle of Wight and Ingleborough

  14. 3D Geological Model for "LUSI" - a Deep Geothermal System

    NASA Astrophysics Data System (ADS)

    Sohrabi, Reza; Jansen, Gunnar; Mazzini, Adriano; Galvan, Boris; Miller, Stephen A.

    2016-04-01

    Geothermal applications require the correct simulation of flow and heat transport processes in porous media, and many of these media, like deep volcanic hydrothermal systems, host a certain degree of fracturing. This work aims to understand the heat and fluid transport within a new-born sedimentary hosted geothermal system, termed Lusi, that began erupting in 2006 in East Java, Indonesia. Our goal is to develop conceptual and numerical models capable of simulating multiphase flow within large-scale fractured reservoirs such as the Lusi region, with fractures of arbitrary size, orientation and shape. Additionally, these models can also address a number of other applications, including Enhanced Geothermal Systems (EGS), CO2 sequestration (Carbon Capture and Storage CCS), and nuclear waste isolation. Fractured systems are ubiquitous, with a wide-range of lengths and scales, making difficult the development of a general model that can easily handle this complexity. We are developing a flexible continuum approach with an efficient, accurate numerical simulator based on an appropriate 3D geological model representing the structure of the deep geothermal reservoir. Using previous studies, borehole information and seismic data obtained in the framework of the Lusi Lab project (ERC grant n°308126), we present here the first 3D geological model of Lusi. This model is calculated using implicit 3D potential field or multi-potential fields, depending on the geological context and complexity. This method is based on geological pile containing the geological history of the area and relationship between geological bodies allowing automatic computation of intersections and volume reconstruction. Based on the 3D geological model, we developed a new mesh algorithm to create hexahedral octree meshes to transfer the structural geological information for 3D numerical simulations to quantify Thermal-Hydraulic-Mechanical-Chemical (THMC) physical processes.

  15. Tracking people and cars using 3D modeling and CCTV.

    PubMed

    Edelman, Gerda; Bijhold, Jurrien

    2010-10-10

    The aim of this study was to find a method for the reconstruction of movements of people and cars using CCTV footage and a 3D model of the environment. A procedure is proposed, in which video streams are synchronized and displayed in a 3D model, by using virtual cameras. People and cars are represented by cylinders and boxes, which are moved in the 3D model, according to their movements as shown in the video streams. The procedure was developed and tested in an experimental setup with test persons who logged their GPS coordinates as a recording of the ground truth. Results showed that it is possible to implement this procedure and to reconstruct movements of people and cars from video recordings. The procedure was also applied to a forensic case. In this work we experienced that more situational awareness was created by the 3D model, which made it easier to track people on multiple video streams. Based on all experiences from the experimental set up and the case, recommendations are formulated for use in practice.

  16. Performance and Cognitive Assessment in 3-D Modeling

    ERIC Educational Resources Information Center

    Fahrer, Nolan E.; Ernst, Jeremy V.; Branoff, Theodore J.; Clark, Aaron C.

    2011-01-01

    The purpose of this study was to investigate identifiable differences between performance and cognitive assessment scores in a 3-D modeling unit of an engineering drafting course curriculum. The study aimed to provide further investigation of the need of skill-based assessments in engineering/technical graphics courses to potentially increase…

  17. Coarse-grained modeling of RNA 3D structure.

    PubMed

    Dawson, Wayne K; Maciejczyk, Maciej; Jankowska, Elzbieta J; Bujnicki, Janusz M

    2016-07-01

    Functional RNA molecules depend on three-dimensional (3D) structures to carry out their tasks within the cell. Understanding how these molecules interact to carry out their biological roles requires a detailed knowledge of RNA 3D structure and dynamics as well as thermodynamics, which strongly governs the folding of RNA and RNA-RNA interactions as well as a host of other interactions within the cellular environment. Experimental determination of these properties is difficult, and various computational methods have been developed to model the folding of RNA 3D structures and their interactions with other molecules. However, computational methods also have their limitations, especially when the biological effects demand computation of the dynamics beyond a few hundred nanoseconds. For the researcher confronted with such challenges, a more amenable approach is to resort to coarse-grained modeling to reduce the number of data points and computational demand to a more tractable size, while sacrificing as little critical information as possible. This review presents an introduction to the topic of coarse-grained modeling of RNA 3D structures and dynamics, covering both high- and low-resolution strategies. We discuss how physics-based approaches compare with knowledge based methods that rely on databases of information. In the course of this review, we discuss important aspects in the reasoning process behind building different models and the goals and pitfalls that can result.

  18. Assessment of 3D Models Used in Contours Studies

    ERIC Educational Resources Information Center

    Alvarez, F. J. Ayala; Parra, E. B. Blazquez; Tubio, F. Montes

    2015-01-01

    This paper presents an experimental research focusing on the view of first year students. The aim is to check the quality of implementing 3D models integrated in the curriculum. We search to determine students' preference between the various means facilitated in order to understand the given subject. Students have been respondents to prove the…

  19. Modeling the Properties of 3D Woven Composites

    NASA Technical Reports Server (NTRS)

    Cox, Brian N.

    1995-01-01

    An extensive study has been completed of the internal geometry, the mechanisms of failure, and the micromechanics of local failure events in graphite/epoxy composites with three dimensional (3D) woven reinforcement. This work has led to the development of models for predicting elastic constants, strength, notch sensitivity, and fatigue life. A summary is presented here.

  20. 3d model for site effect assessment at Nice (France)

    NASA Astrophysics Data System (ADS)

    Bertrand, E.; Courrioux, G.; Bourgine, B.; Bour, M.; Guillen, A.; Mouroux, P.; Devaux, E.; Duval, A. M.

    2003-04-01

    Assessment of lithologic site effects is based on an accurate knowledge of properties and geometry of superficial geological formations, i.e. ideally a 3D-4G subsurface model (Geology, Geomorphology, Geophysics, Geotechnics). Such a model has been achieved using a 3D geomodeler ("Geological Editor" developed at BRGM) that allows building 3D volumes of geological formations starting from drill-holes data, sections, and geological maps. This software uses a pseudo-stratigraphic pile in order to reproduce geological history and structural relationships (erosion, deposit). The interpolation is achieved through a 3D potential field. A geostatistical formulation allows to consider data points of a geological limit as equipotential, and sructural dips as gradient inputs for the 3D field interpolation. Then isosurfaces corresponding to each limit are combined using formation relationships to provide volumic models of geological formations. The first task was to identify the relevant geological formations underlying in Nice area. In a first approach Mesozoic bedrock, Pliocene bedrock, and Quaternary alluvial deposits have been distinguished considering their seismic properties. Then alluvions have been subdivided into 9 groups according to their lithology and granulometry. Modelling has been performed considering 2 major erosion surfaces, post-Mesozoic and post-Pliocene. The succession of Quaternary alluviums have been considered as "onlap deposits". Given adjacent lithologies contained in maps and drill holes, these relations lead to logical identification of the roof of formations to be interpolated. The distribution of modeled geological formations can be visualised in 3 dimensions or in 2D sections. Besides the visual interest of 3D representations, the model is first used to build a series of earth columns over a 50m/50m 2D grid. A statistical analysis allowed to identify 73 existing configurations in the Nice district area. Among these, only 15 configurations

  1. Robust 3D reconstruction system for human jaw modeling

    NASA Astrophysics Data System (ADS)

    Yamany, Sameh M.; Farag, Aly A.; Tazman, David; Farman, Allan G.

    1999-03-01

    This paper presents a model-based vision system for dentistry that will replace traditional approaches used in diagnosis, treatment planning and surgical simulation. Dentistry requires accurate 3D representation of the teeth and jaws for many diagnostic and treatment purposes. For example orthodontic treatment involves the application of force systems to teeth over time to correct malocclusion. In order to evaluate tooth movement progress, the orthodontists monitors this movement by means of visual inspection, intraoral measurements, fabrication of plastic models, photographs and radiographs, a process which is both costly and time consuming. In this paper an integrate system has been developed to record the patient's occlusion using computer vision. Data is acquired with an intraoral video camera. A modified shape from shading (SFS) technique, using perspective projection and camera calibration, is used to extract accurate 3D information from a sequence of 2D images of the jaw. A new technique for 3D data registration, using a Grid Closest Point transform and genetic algorithms, is used to register the SFS output. Triangulization is then performed, and a solid 3D model is obtained via a rapid prototype machine.

  2. Use Models like Maps in a 3D SDI

    NASA Astrophysics Data System (ADS)

    Gietzel, Jan; Gabriel, Paul; Schaeben, Helmut; Le, Hai Ha

    2013-04-01

    Digital geological applications have become 3D up to 4D modelling of the underground. The modellers are working very heterogeneously in terms of its applied software systems. On the other hand the 3D/4D modelling of the subsurface has become part of the geological surveys all around the world. This implies a wide spread group of users working in different institutions aiming to work together on one subsurface model. Established 3D/4D-modelling software systems mainly use a file based approach to store data, which is in a high contrast to the needs of a central administrated and network based data transfer approach. At the department of geophysics and geo information sciences at the Technical University Bergakademie Freiberg, the GST system for managing 3D and 4D geosciences data in a databases system was developed and is now continued by the company GiGa infosystems. The GST-Framework includes a storage engine, a web service for sharing and a number of client software including a browser based client interface for visualising, accessing and manipulating geological CAD data. Including a check out system GST supports multi user editing on huge models, designed to manage seamless high resolution models of the subsurface. While working on complex projects various software is used for the creation of the model, the prediction of properties and final simulation. A problem rising from the use of several software is the interoperability of the models. Due to conversion errors different working groups use mainly different raw data. This results in different models, which have to be corrected with additional effort. One platform sharing the models is strongly demanded. One high potential solution is a centralized and software independent storage, which will be presented.

  3. 3D Geological modelling - towards a European level infrastructure

    NASA Astrophysics Data System (ADS)

    Lee, Kathryn A.; van der Krogt, Rob; Busschers, Freek S.

    2013-04-01

    The joint European Geological Surveys are preparing the ground for a "European Geological Data Infrastructure" (EGDI), under the framework of the FP7-project EGDI-Scope. This scoping study, started in June 2012, for a pan-European e-Infrastructure is based on the successes of earlier joint projects including 'OneGeology-Europe' and aims to provide the backbone for serving interoperable, geological data currently held by European Geological Surveys. Also data from past, ongoing and future European projects will be incorporated. The scope will include an investigation of the functional and technical requirements for serving 3D geological models and will look to research the potential for providing a framework to integrate models at different scales, and form a structure for enabling the development of new and innovative model delivery mechanisms. The EGDI-scope project encourages pan-European inter-disciplinary collaboration between all European Geological Surveys. It aims to enhance emerging web based technologies that will facilitate the delivery of geological data to user communities involved in European policy making and international industry, but also to geoscientific research communities and the general public. Therefore, stakeholder input and communication is imperative to the success, as is the collaboration with all the Geological Surveys of Europe. The most important functional and technical requirements for delivery of such information at pan-European level will be derived from exchanges with relevant European stakeholder representatives and providers of geological data. For handling and delivering 3D geological model data the project will need to address a number of strategic issues: • Which are the most important issues and queries for the relevant stakeholders, requiring 3D geological models? How can this be translated to functional requirements for development and design of an integrated European application? • How to handle the very large

  4. Quasi-3D Multi-scale Modeling Framework Development

    NASA Astrophysics Data System (ADS)

    Arakawa, A.; Jung, J.

    2008-12-01

    When models are truncated in or near an energetically active range of the spectrum, model physics must be changed as the resolution changes. The model physics of GCMs and that of CRMs are, however, quite different from each other and at present there is no unified formulation of model physics that automatically provides transition between these model physics. The Quasi-3D (Q3D) Multi-scale Modeling Framework (MMF) is an attempt to bridge this gap. Like the recently proposed Heterogeneous Multiscale Method (HMM) (E and Engquist 2003), MMF combines a macroscopic model, GCM, and a microscopic model, CRM. Unlike the traditional multiscale methods such as the multi-grid and adapted mesh refinement techniques, HMM and MMF are for solving multi-physics problems. They share the common objective "to design combined macroscopic-microscopic computational methods that are much more efficient than solving the full microscopic model and at the same time give the information we need" (E et al. 2008). The question is then how to meet this objective in practice, which can be highly problem dependent. In HHM, the efficiency is gained typically by localization of the microscale problem. Following the pioneering work by Grabowski and Smolarkiewicz (1999) and Grabowski (2001), MMF takes advantage of the fact that 2D CRMs are reasonably successful in simulating deep clouds. In this approach, the efficiency is gained by sacrificing the three-dimensionality of cloud-scale motion. It also "localizes" the algorithm through embedding a CRM in each GCM grid box using cyclic boundary condition. The Q3D MMF is an attempt to reduce the expense due to these constraints by partially including the cloud-scale 3D effects and extending the CRM beyond individual GCM grid boxes. As currently formulated, the Q3D MMF is a 4D estimation/prediction framework that combines a GCM with a 3D anelastic cloud-resolving vector vorticity equation model (VVM) applied to a network of horizontal grids. The network

  5. Use and perceived benefits and barriers of QSAR models for REACH: findings from a questionnaire to stakeholders

    PubMed Central

    2012-01-01

    The ORCHESTRA online questionnaire on “benefits and barriers to the use of QSAR methods” addressed the academic, consultant, regulatory and industry communities potentially interested by QSAR methods in the context of REACH. Replies from more than 60 stakeholders produced some insights on the actual application of QSAR methods, and how to improve their use. Respondents state in majority that they have used QSAR methods. All have some future plans to test or use QSAR methods in accordance with their stakeholder role. The stakeholder respondents cited a total of 28 models, methods or software that they have actually applied. The three most frequently cited suites, used moreover by all the stakeholder categories, are the OECD Toolbox, EPISuite and CAESAR; all are free tools. Results suggest that stereotyped assumptions about the barriers to application of QSAR may be incorrect. Economic costs (including potential delays) are not found to be a major barrier. And only one respondent “prefers” traditional, well-known and accepted toxicological assessment methods. Information and guidance may be the keys to reinforcing use of QSAR models. Regulators appear most interested in obtaining clear explanation of the basis of the models, to provide a solid basis for decisions. Scientists appear most interested in the exploration of the scientific capabilities of the QSAR approach. Industry shows interest in obtaining reassurance that appropriate uses of QSAR will be accepted by regulators. PMID:23244245

  6. 3-D HYDRODYNAMIC MODELING IN A GEOSPATIAL FRAMEWORK

    SciTech Connect

    Bollinger, J; Alfred Garrett, A; Larry Koffman, L; David Hayes, D

    2006-08-24

    3-D hydrodynamic models are used by the Savannah River National Laboratory (SRNL) to simulate the transport of thermal and radionuclide discharges in coastal estuary systems. Development of such models requires accurate bathymetry, coastline, and boundary condition data in conjunction with the ability to rapidly discretize model domains and interpolate the required geospatial data onto the domain. To facilitate rapid and accurate hydrodynamic model development, SRNL has developed a pre- and post-processor application in a geospatial framework to automate the creation of models using existing data. This automated capability allows development of very detailed models to maximize exploitation of available surface water radionuclide sample data and thermal imagery.

  7. 3D model of the Bernese Part of the Swiss Molasse Basin: visualization of uncertainties in a 3D model

    NASA Astrophysics Data System (ADS)

    Mock, Samuel; Allenbach, Robin; Reynolds, Lance; Wehrens, Philip; Kurmann-Matzenauer, Eva; Kuhn, Pascal; Michael, Salomè; Di Tommaso, Gennaro; Herwegh, Marco

    2016-04-01

    The Swiss Molasse Basin comprises the western and central part of the North Alpine Foreland Basin. In recent years it has come under closer scrutiny due to its promising geopotentials such as geothermal energy and CO2 sequestration. In order to adress these topics good knowledge of the subsurface is a key prerequisite. For that matter, geological 3D models serve as valuable tools. In collaboration with the Swiss Geological Survey (swisstopo) and as part of the project GeoMol CH, a geological 3D model of the Swiss Molasse Basin in the Canton of Bern has been built. The model covers an area of 1810 km2and reaches depth of up to 6.7 km. It comprises 10 major Cenozoic and Mesozoic units and numerous faults. The 3D model is mainly based on 2D seismic data complemented by information from few deep wells. Additionally, data from geological maps and profiles were used for refinement at shallow depths. In total, 1163 km of reflection seismic data, along 77 seismic lines, have been interpreted by different authors with respect to stratigraphy and structures. Both, horizons and faults, have been interpreted in 2D and modelled in 3D using IHS's Kingdom Suite and Midland Valley's MOVE software packages, respectively. Given the variable degree of subsurface information available, each 3D model is subject of uncertainty. With the primary input data coming from interpretation of reflection seismic data, a variety of uncertainties comes into play. Some of them are difficult to address (e.g. author's style of interpretation) while others can be quantified (e.g. mis-tie correction, well-tie). An important source of uncertainties is the quality of seismic data; this affects the traceability and lateral continuation of seismic reflectors. By defining quality classes we can semi-quantify this source of uncertainty. In order to visualize the quality and density of the input data in a meaningful way, we introduce quality-weighted data density maps. In combination with the geological 3D

  8. 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

  9. 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

  10. Imidazolium Ionic Liquids as Potential Anti-Candida Inhibitors: QSAR Modeling and Experimental Studies.

    PubMed

    Hodyna, Diana; Kovalishyn, Vasyl; Rogalsky, Sergiy; Blagodatnyi, Volodymyr; Metelytsia, Larisa

    2016-01-01

    Quantitative structure-activity relationships (QSAR) of imidazolium ionic liquids (ILs) as inhibitors of C. albicans collection strains (IOA-109, KCTC 1940, ATCC 10231) have been studied. Predictive QSAR models were built using different descriptor sets for a set of 88 ionic liquids with known minimum inhibitory concentrations (MIC) against C. albicans. We applied the state-of-the-art QSAR methodologies such as WEKA Random Forest (RF) as a binary classifier, Associative Neural Networks (ASNN) and k-Nearest Neighbors (k-NN) to build continuum non-linear regression models. The obtained models were validated using a 5-fold cross-validation approach and resulted in the prediction accuracies of 80% ± 5.0 for the classification models and q2 = 0.73-0.87 for the non-linear regression models. Biological testing of newly synthesized 1,3-dialkylimidazolium ionic liquids with predicted activity was performed by disco-diffusion method against C. albicans ATCC 10231 M885 strain and clinical isolates C. albicans, C. krusei and C. glabrata strains. The high percentage of coincidence between the QSAR predictions and the experimental results confirmed the high predictive power of the developed QSAR models within the applicability domain of new imidazolium ionic liquids. PMID:27160290

  11. Imidazolium Ionic Liquids as Potential Anti-Candida Inhibitors: QSAR Modeling and Experimental Studies.

    PubMed

    Hodyna, Diana; Kovalishyn, Vasyl; Rogalsky, Sergiy; Blagodatnyi, Volodymyr; Metelytsia, Larisa

    2016-01-01

    Quantitative structure-activity relationships (QSAR) of imidazolium ionic liquids (ILs) as inhibitors of C. albicans collection strains (IOA-109, KCTC 1940, ATCC 10231) have been studied. Predictive QSAR models were built using different descriptor sets for a set of 88 ionic liquids with known minimum inhibitory concentrations (MIC) against C. albicans. We applied the state-of-the-art QSAR methodologies such as WEKA Random Forest (RF) as a binary classifier, Associative Neural Networks (ASNN) and k-Nearest Neighbors (k-NN) to build continuum non-linear regression models. The obtained models were validated using a 5-fold cross-validation approach and resulted in the prediction accuracies of 80% ± 5.0 for the classification models and q2 = 0.73-0.87 for the non-linear regression models. Biological testing of newly synthesized 1,3-dialkylimidazolium ionic liquids with predicted activity was performed by disco-diffusion method against C. albicans ATCC 10231 M885 strain and clinical isolates C. albicans, C. krusei and C. glabrata strains. The high percentage of coincidence between the QSAR predictions and the experimental results confirmed the high predictive power of the developed QSAR models within the applicability domain of new imidazolium ionic liquids.

  12. Towards a 3d Spatial Urban Energy Modelling Approach

    NASA Astrophysics Data System (ADS)

    Bahu, J.-M.; Koch, A.; Kremers, E.; Murshed, S. M.

    2013-09-01

    Today's needs to reduce the environmental impact of energy use impose dramatic changes for energy infrastructure and existing demand patterns (e.g. buildings) corresponding to their specific context. In addition, future energy systems are expected to integrate a considerable share of fluctuating power sources and equally a high share of distributed generation of electricity. Energy system models capable of describing such future systems and allowing the simulation of the impact of these developments thus require a spatial representation in order to reflect the local context and the boundary conditions. This paper describes two recent research approaches developed at EIFER in the fields of (a) geo-localised simulation of heat energy demand in cities based on 3D morphological data and (b) spatially explicit Agent-Based Models (ABM) for the simulation of smart grids. 3D city models were used to assess solar potential and heat energy demand of residential buildings which enable cities to target the building refurbishment potentials. Distributed energy systems require innovative modelling techniques where individual components are represented and can interact. With this approach, several smart grid demonstrators were simulated, where heterogeneous models are spatially represented. Coupling 3D geodata with energy system ABMs holds different advantages for both approaches. On one hand, energy system models can be enhanced with high resolution data from 3D city models and their semantic relations. Furthermore, they allow for spatial analysis and visualisation of the results, with emphasis on spatially and structurally correlations among the different layers (e.g. infrastructure, buildings, administrative zones) to provide an integrated approach. On the other hand, 3D models can benefit from more detailed system description of energy infrastructure, representing dynamic phenomena and high resolution models for energy use at component level. The proposed modelling strategies

  13. 3-D model-based tracking for UAV indoor localization.

    PubMed

    Teulière, Céline; Marchand, Eric; Eck, Laurent

    2015-05-01

    This paper proposes a novel model-based tracking approach for 3-D localization. One main difficulty of standard model-based approach lies in the presence of low-level ambiguities between different edges. In this paper, given a 3-D model of the edges of the environment, we derive a multiple hypotheses tracker which retrieves the potential poses of the camera from the observations in the image. We also show how these candidate poses can be integrated into a particle filtering framework to guide the particle set toward the peaks of the distribution. Motivated by the UAV indoor localization problem where GPS signal is not available, we validate the algorithm on real image sequences from UAV flights.

  14. 3-D model-based tracking for UAV indoor localization.

    PubMed

    Teulière, Céline; Marchand, Eric; Eck, Laurent

    2015-05-01

    This paper proposes a novel model-based tracking approach for 3-D localization. One main difficulty of standard model-based approach lies in the presence of low-level ambiguities between different edges. In this paper, given a 3-D model of the edges of the environment, we derive a multiple hypotheses tracker which retrieves the potential poses of the camera from the observations in the image. We also show how these candidate poses can be integrated into a particle filtering framework to guide the particle set toward the peaks of the distribution. Motivated by the UAV indoor localization problem where GPS signal is not available, we validate the algorithm on real image sequences from UAV flights. PMID:25099967

  15. 3D Multispectral Light Propagation Model For Subcutaneous Veins Imaging

    SciTech Connect

    Paquit, Vincent C; Price, Jeffery R; Meriaudeau, Fabrice; Tobin Jr, Kenneth William

    2008-01-01

    In this paper, we describe a new 3D light propagation model aimed at understanding the effects of various physiological properties on subcutaneous vein imaging. In particular, we build upon the well known MCML (Monte Carlo Multi Layer) code and present a tissue model that improves upon the current state-of-the-art by: incorporating physiological variation, such as melanin concentration, fat content, and layer thickness; including veins of varying depth and diameter; using curved surfaces from real arm shapes; and modeling the vessel wall interface. We describe our model, present results from the Monte Carlo modeling, and compare these results with those obtained with other Monte Carlo methods.

  16. Generation and use of human 3D-CAD models

    NASA Astrophysics Data System (ADS)

    Grotepass, Juergen; Speyer, Hartmut; Kaiser, Ralf

    2002-05-01

    Individualized Products are one of the ten mega trends of the 21st Century with human modeling as the key issue for tomorrow's design and product development. The use of human modeling software for computer based ergonomic simulations within the production process increases quality while reducing costs by 30- 50 percent and shortening production time. This presentation focuses on the use of human 3D-CAD models for both, the ergonomic design of working environments and made to measure garment production. Today, the entire production chain can be designed, individualized models generated and analyzed in 3D computer environments. Anthropometric design for ergonomics is matched to human needs, thus preserving health. Ergonomic simulation includes topics as human vision, reachability, kinematics, force and comfort analysis and international design capabilities. In German more than 17 billions of Mark are moved to other industries, because clothes do not fit. Individual clothing tailored to the customer's preference means surplus value, pleasure and perfect fit. The body scanning technology is the key to generation and use of human 3D-CAD models for both, the ergonomic design of working environments and made to measure garment production.

  17. Method for modeling post-mortem biometric 3D fingerprints

    NASA Astrophysics Data System (ADS)

    Rajeev, Srijith; Shreyas, Kamath K. M.; Agaian, Sos S.

    2016-05-01

    Despite the advancements of fingerprint recognition in 2-D and 3-D domain, authenticating deformed/post-mortem fingerprints continue to be an important challenge. Prior cleansing and reconditioning of the deceased finger is required before acquisition of the fingerprint. The victim's finger needs to be precisely and carefully operated by a medium to record the fingerprint impression. This process may damage the structure of the finger, which subsequently leads to higher false rejection rates. This paper proposes a non-invasive method to perform 3-D deformed/post-mortem finger modeling, which produces a 2-D rolled equivalent fingerprint for automated verification. The presented novel modeling method involves masking, filtering, and unrolling. Computer simulations were conducted on finger models with different depth variations obtained from Flashscan3D LLC. Results illustrate that the modeling scheme provides a viable 2-D fingerprint of deformed models for automated verification. The quality and adaptability of the obtained unrolled 2-D fingerprints were analyzed using NIST fingerprint software. Eventually, the presented method could be extended to other biometric traits such as palm, foot, tongue etc. for security and administrative applications.

  18. 3D modeling of dual-gate FinFET.

    PubMed

    Mil'shtein, Samson; Devarakonda, Lalitha; Zanchi, Brian; Palma, John

    2012-01-01

    The tendency to have better control of the flow of electrons in a channel of field-effect transistors (FETs) did lead to the design of two gates in junction field-effect transistors, field plates in a variety of metal semiconductor field-effect transistors and high electron mobility transistors, and finally a gate wrapping around three sides of a narrow fin-shaped channel in a FinFET. With the enhanced control, performance trends of all FETs are still challenged by carrier mobility dependence on the strengths of the electrical field along the channel. However, in cases when the ratio of FinFET volume to its surface dramatically decreases, one should carefully consider the surface boundary conditions of the device. Moreover, the inherent non-planar nature of a FinFET demands 3D modeling for accurate analysis of the device performance. Using the Silvaco modeling tool with quantization effects, we modeled a physical FinFET described in the work of Hisamoto et al. (IEEE Tran. Elec. Devices 47:12, 2000) in 3D. We compared it with a 2D model of the same device. We demonstrated that 3D modeling produces more accurate results. As 3D modeling results came close to experimental measurements, we made the next step of the study by designing a dual-gate FinFET biased at Vg1 >Vg2. It is shown that the dual-gate FinFET carries higher transconductance than the single-gate device. PMID:23148493

  19. 3D cartographic modeling of the Alpine arc

    NASA Astrophysics Data System (ADS)

    Vouillamoz, Naomi; Sue, Christian; Champagnac, Jean-Daniel; Calcagno, Philippe

    2012-12-01

    We built a 3D cartography of the Alpine arc, a highly non-cylindrical mountain belt, using the 3D GeoModeller of the BRGM (French geological survey). The model allows to handle the large-scale 3D structure of seventeen major crustal units of the belt (from the lower crust to the sedimentary cover nappes), and two main discontinuities (the Insubric Line and the Crustal Penninic Front). It provides a unique document to better understand their structural relationships and to produce new sections. The study area comprises the western Alpine arc, from the Jura to the Northwest, up to the Bergell granite intrusion and the Lepontine Dome to the East, and is limited to the South by the Ligurian basin. The model is limited vertically 10 km above sea level at the top, and the moho interface at the bottom. We discarded the structural relationships between the Alps sensus stricto and the surrounding geodynamic systems such as the Rhine graben or the connection with the Apennines. The 3D-model is based on the global integration of various data such as the DEM of the Alps, the moho isobaths, the simplified geological and tectonic maps of the belt, the crustal cross-sections ECORS-CROP and NFP-20, and complementary cross-sections specifically built to precise local complexities. The database has first been integrated in a GIS-project to prepare their implementation in the GeoModeller, by homogenizing the different spatial referencing systems. The global model is finally interpolated from all these data, using the potential field method. The final document is a new tri-dimensional cartography that would be used as input for further alpine studies.

  20. Interchain coupling and 3D modeling of trans-polyacetylene

    SciTech Connect

    Bronold, F.; Saxena, A.; Bishop, A.R.

    1992-01-01

    In spite of the success of the SSH model for trans-polyacetylene in interpreting many experimental results (e.g. optical and magnetic properties) there remain some aspects of the real material which are outside the scope of the simple 1D model. Especially ordering phenomena of doped and undoped trans-polyacetylene as well as transport properties (e.g. electronic and thermal conductivity) are beyond a 1D description. There are many attempts to construct a transport theory for this novel class of materials using solitons or polaxons as the basic ingredients. But so far it is not yet clear whether these typical 1D excitations still exist in crystalline transpolyacetylene. Therefore, to clarify the role which intrinsic self-localized nonlinear excitations characteristic of 1D models play in the bulk (3D) material, we study the stability of a polaronic excitation against interchain coupling. As a preliminary step we consider first two coupled t-(CH){sub x}-chains where the {pi}-electrons are allowed to hop from one chain to the other. Then we introduce a 3D generalization of the SSH model and study a polaron in a 3D crystalline environment.

  1. Interchain coupling and 3D modeling of trans-polyacetylene

    SciTech Connect

    Bronold, F.; Saxena, A.; Bishop, A.R.

    1992-09-01

    In spite of the success of the SSH model for trans-polyacetylene in interpreting many experimental results (e.g. optical and magnetic properties) there remain some aspects of the real material which are outside the scope of the simple 1D model. Especially ordering phenomena of doped and undoped trans-polyacetylene as well as transport properties (e.g. electronic and thermal conductivity) are beyond a 1D description. There are many attempts to construct a transport theory for this novel class of materials using solitons or polaxons as the basic ingredients. But so far it is not yet clear whether these typical 1D excitations still exist in crystalline transpolyacetylene. Therefore, to clarify the role which intrinsic self-localized nonlinear excitations characteristic of 1D models play in the bulk (3D) material, we study the stability of a polaronic excitation against interchain coupling. As a preliminary step we consider first two coupled t-(CH){sub x}-chains where the {pi}-electrons are allowed to hop from one chain to the other. Then we introduce a 3D generalization of the SSH model and study a polaron in a 3D crystalline environment.

  2. 3-D Numerical Modeling of a Complex Salt Structure

    SciTech Connect

    House, L.; Larsen, S.; Bednar, J.B.

    2000-02-17

    Reliably processing, imaging, and interpreting seismic data from areas with complicated structures, such as sub-salt, requires a thorough understanding of elastic as well as acoustic wave propagation. Elastic numerical modeling is an essential tool to develop that understanding. While 2-D elastic modeling is in common use, 3-D elastic modeling has been too computationally intensive to be used routinely. Recent advances in computing hardware, including commodity-based hardware, have substantially reduced computing costs. These advances are making 3-D elastic numerical modeling more feasible. A series of example 3-D elastic calculations were performed using a complicated structure, the SEG/EAGE salt structure. The synthetic traces show that the effects of shear wave propagation can be important for imaging and interpretation of images, and also for AVO and other applications that rely on trace amplitudes. Additional calculations are needed to better identify and understand the complex wave propagation effects produced in complicated structures, such as the SEG/EAGE salt structure.

  3. CityGML - Interoperable semantic 3D city models

    NASA Astrophysics Data System (ADS)

    Gröger, Gerhard; Plümer, Lutz

    2012-07-01

    CityGML is the international standard of the Open Geospatial Consortium (OGC) for the representation and exchange of 3D city models. It defines the three-dimensional geometry, topology, semantics and appearance of the most relevant topographic objects in urban or regional contexts. These definitions are provided in different, well-defined Levels-of-Detail (multiresolution model). The focus of CityGML is on the semantical aspects of 3D city models, its structures, taxonomies and aggregations, allowing users to employ virtual 3D city models for advanced analysis and visualization tasks in a variety of application domains such as urban planning, indoor/outdoor pedestrian navigation, environmental simulations, cultural heritage, or facility management. This is in contrast to purely geometrical/graphical models such as KML, VRML, or X3D, which do not provide sufficient semantics. CityGML is based on the Geography Markup Language (GML), which provides a standardized geometry model. Due to this model and its well-defined semantics and structures, CityGML facilitates interoperable data exchange in the context of geo web services and spatial data infrastructures. Since its standardization in 2008, CityGML has become used on a worldwide scale: tools from notable companies in the geospatial field provide CityGML interfaces. Many applications and projects use this standard. CityGML is also having a strong impact on science: numerous approaches use CityGML, particularly its semantics, for disaster management, emergency responses, or energy-related applications as well as for visualizations, or they contribute to CityGML, improving its consistency and validity, or use CityGML, particularly its different Levels-of-Detail, as a source or target for generalizations. This paper gives an overview of CityGML, its underlying concepts, its Levels-of-Detail, how to extend it, its applications, its likely future development, and the role it plays in scientific research. Furthermore, its

  4. Lattice percolation approach to 3D modeling of tissue aging

    NASA Astrophysics Data System (ADS)

    Gorshkov, Vyacheslav; Privman, Vladimir; Libert, Sergiy

    2016-11-01

    We describe a 3D percolation-type approach to modeling of the processes of aging and certain other properties of tissues analyzed as systems consisting of interacting cells. Lattice sites are designated as regular (healthy) cells, senescent cells, or vacancies left by dead (apoptotic) cells. The system is then studied dynamically with the ongoing processes including regular cell dividing to fill vacant sites, healthy cells becoming senescent or dying, and senescent cells dying. Statistical-mechanics description can provide patterns of time dependence and snapshots of morphological system properties. The developed theoretical modeling approach is found not only to corroborate recent experimental findings that inhibition of senescence can lead to extended lifespan, but also to confirm that, unlike 2D, in 3D senescent cells can contribute to tissue's connectivity/mechanical stability. The latter effect occurs by senescent cells forming the second infinite cluster in the regime when the regular (healthy) cell's infinite cluster still exists.

  5. The 3D model control of image processing

    NASA Technical Reports Server (NTRS)

    Nguyen, An H.; Stark, Lawrence

    1989-01-01

    Telerobotics studies remote control of distant robots by a human operator using supervisory or direct control. Even if the robot manipulators has vision or other senses, problems arise involving control, communications, and delay. The communication delays that may be expected with telerobots working in space stations while being controlled from an Earth lab have led to a number of experiments attempting to circumvent the problem. This delay in communication is a main motivating factor in moving from well understood instantaneous hands-on manual control to less well understood supervisory control; the ultimate step would be the realization of a fully autonomous robot. The 3-D model control plays a crucial role in resolving many conflicting image processing problems that are inherent in resolving in the bottom-up approach of most current machine vision processes. The 3-D model control approach is also capable of providing the necessary visual feedback information for both the control algorithms and for the human operator.

  6. 3D root canal modeling for advanced endodontic treatment

    NASA Astrophysics Data System (ADS)

    Hong, Shane Y.; Dong, Janet

    2002-06-01

    More than 14 million teeth receive endodontic (root canal) treatment annually. Before a clinician's inspection and diagnosis, destructive access preparation by removing teeth crown and dentin is usually needed. This paper presents a non-invasive method for accessing internal tooth geometry by building 3-D tooth model from 2-D radiographic and endoscopic images to be used for an automatic prescription system of computer-aided treatment procedure planning, and for the root canal preparation by an intelligent micro drilling machine with on-line monitoring. It covers the techniques specific for dental application in the radiographic images acquirement, image enhancement, image segmentation and feature recognition, distance measurement and calibration, merging 2D image into 3D mathematical model representation and display. Included also are the methods to form references for irregular teeth geometry and to do accurately measurement with self-calibration.

  7. Tuning HERG out: antitarget QSAR models for drug development.

    PubMed

    Braga, Rodolpho C; Alves, Vinicius M; Silva, Meryck F B; Muratov, Eugene; Fourches, Denis; Tropsha, Alexander; Andrade, Carolina H

    2014-01-01

    Several non-cardiovascular drugs have been withdrawn from the market due to their inhibition of hERG K+ channels that can potentially lead to severe heart arrhythmia and death. As hERG safety testing is a mandatory FDArequired procedure, there is a considerable interest for developing predictive computational tools to identify and filter out potential hERG blockers early in the drug discovery process. In this study, we aimed to generate predictive and well-characterized quantitative structure-activity relationship (QSAR) models for hERG blockage using the largest publicly available dataset of 11,958 compounds from the ChEMBL database. The models have been developed and validated according to OECD guidelines using four types of descriptors and four different machine-learning techniques. The classification accuracies discriminating blockers from non-blockers were as high as 0.83-0.93 on external set. Model interpretation revealed several SAR rules, which can guide structural optimization of some hERG blockers into non-blockers. We have also applied the generated models for screening the World Drug Index (WDI) database and identify putative hERG blockers and non-blockers among currently marketed drugs. The developed models can reliably identify blockers and non-blockers, which could be useful for the scientific community. A freely accessible web server has been developed allowing users to identify putative hERG blockers and non-blockers in chemical libraries of their interest (http://labmol.farmacia.ufg.br/predherg).

  8. Modeling 3D faces from samplings via compressive sensing

    NASA Astrophysics Data System (ADS)

    Sun, Qi; Tang, Yanlong; Hu, Ping

    2013-07-01

    3D data is easier to acquire for family entertainment purpose today because of the mass-production, cheapness and portability of domestic RGBD sensors, e.g., Microsoft Kinect. However, the accuracy of facial modeling is affected by the roughness and instability of the raw input data from such sensors. To overcome this problem, we introduce compressive sensing (CS) method to build a novel 3D super-resolution scheme to reconstruct high-resolution facial models from rough samples captured by Kinect. Unlike the simple frame fusion super-resolution method, this approach aims to acquire compressed samples for storage before a high-resolution image is produced. In this scheme, depth frames are firstly captured and then each of them is measured into compressed samples using sparse coding. Next, the samples are fused to produce an optimal one and finally a high-resolution image is recovered from the fused sample. This framework is able to recover 3D facial model of a given user from compressed simples and this can reducing storage space as well as measurement cost in future devices e.g., single-pixel depth cameras. Hence, this work can potentially be applied into future applications, such as access control system using face recognition, and smart phones with depth cameras, which need high resolution and little measure time.

  9. STELLOPT modeling of the 3D diagnostic response in ITER

    NASA Astrophysics Data System (ADS)

    Lazerson, S. A.; Chapman, I. T.

    2013-08-01

    The ITER three-dimensional (3D) diagnostic response to an n = 3 resonant magnetic perturbation (RMP) is modeled using the STELLOPT code. The in-vessel coils apply a RMP field which generates a 4 cm edge displacement from axisymmetry as modeled by the VMEC 3D equilibrium code. Forward modeling of flux loop and magnetic probe response with the DIAGNO code indicates up to 20% changes in measured plasma signals. Simulated LIDAR measurements of electron temperature indicate 2 cm shifts on the low-field side of the plasma. This suggests that the ITER diagnostic will be able to diagnose the 3D structure of the equilibria. Notice: This paper has been authored by Princeton University under Contract Number DE-AC02-09CH11466 with the US Department of Energy. The publisher, by accepting the paper for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this Paper, or allow others to do so, for United States Government purposes.

  10. Modelling of 3D fractured geological systems - technique and application

    NASA Astrophysics Data System (ADS)

    Cacace, M.; Scheck-Wenderoth, M.; Cherubini, Y.; Kaiser, B. O.; Bloecher, G.

    2011-12-01

    All rocks in the earth's crust are fractured to some extent. Faults and fractures are important in different scientific and industry fields comprising engineering, geotechnical and hydrogeological applications. Many petroleum, gas and geothermal and water supply reservoirs form in faulted and fractured geological systems. Additionally, faults and fractures may control the transport of chemical contaminants into and through the subsurface. Depending on their origin and orientation with respect to the recent and palaeo stress field as well as on the overall kinematics of chemical processes occurring within them, faults and fractures can act either as hydraulic conductors providing preferential pathways for fluid to flow or as barriers preventing flow across them. The main challenge in modelling processes occurring in fractured rocks is related to the way of describing the heterogeneities of such geological systems. Flow paths are controlled by the geometry of faults and their open void space. To correctly simulate these processes an adequate 3D mesh is a basic requirement. Unfortunately, the representation of realistic 3D geological environments is limited by the complexity of embedded fracture networks often resulting in oversimplified models of the natural system. A technical description of an improved method to integrate generic dipping structures (representing faults and fractures) into a 3D porous medium is out forward. The automated mesh generation algorithm is composed of various existing routines from computational geometry (e.g. 2D-3D projection, interpolation, intersection, convex hull calculation) and meshing (e.g. triangulation in 2D and tetrahedralization in 3D). All routines have been combined in an automated software framework and the robustness of the approach has been tested and verified. These techniques and methods can be applied for fractured porous media including fault systems and therefore found wide applications in different geo-energy related

  11. West Flank Coso, CA FORGE 3D geologic model

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

    This is an x,y,z file of the West Flank FORGE 3D geologic model. Model created in Earthvision by Dynamic Graphic Inc. The model was constructed with a grid spacing of 100 m. Geologic surfaces were extrapolated from the input data using a minimum tension gridding algorithm. The data file is tabular data in a text file, with lithology data associated with X,Y,Z grid points. All the relevant information is in the file header (the spatial reference, the projection etc.) In addition all the fields in the data file are identified in the header.

  12. 3D modelling of the Black Sea ecosystem

    NASA Astrophysics Data System (ADS)

    Capet, A.; Gregoire, M.; Beckers, J.-M.; Joassin, P.; Naithani, J.; Soetart, K.

    2009-04-01

    A coupled physical-biogeochemical model has been developed to simulate the ecosystem of the Black Sea at the end of the 80's when eutrophication and invasion by gelatinous organisms seriously affected the stability and dynamics of the system. The biogeochemical model describes the cycle of carbon, nitrogen, silicate, oxygen and phosphorus through the foodweb from bacteria to gelatinous carnivores and explicitly represents processes in the anoxic layer down to the bottom. For calibration and analyses purposes, the coupled model has first been run in 1D at several places in the Black Sea. The biogeochemical model involves some hundred parameters which have been first calibrated by hand using published values. Then, an identifiability analysis has been performed in order to determine a subset of 15 identifiable parameters. An automatic calibration subroutine has been used to fine tune these parameters. In 1D, the model solution exhibits a complex dynamics with several years of transient adjustment. This complexity is imparted by the explicit modelling of top predators. The model has been calibrated and validated using a large set of data available in the Black Sea TU Ocean Base. The calibrated biogeochemical model is implemented in a 3D hydrodynamical model of the Black Sea. Results of these 3D simulations will be presented and compared with maps of in-situ data reconstructed from available data base using the software DIVA (Data Interpolation and Variational analysis).

  13. Northern California Seismic Attenuation: 3-D Qp and Qs models

    NASA Astrophysics Data System (ADS)

    Eberhart-Phillips, D. M.

    2015-12-01

    The northern California crust exhibits a wide range of rock types and deformation processes which produce pronounced heterogeneity in regional attenuation. Using local earthquakes, 3-D Qp and Qs crustal models have been obtained for this region which includes the San Andreas fault system, the Central Valley, the Sierra Nevada batholith, and the Mendocino subduction volcanic system. Path attenuation t* values were determined from P and S spectra of 959 spatially distributed earthquakes, magnitude 2.5-6.0 from 2005-2014, using 1254 stations from NCEDC networks and IRIS Mendocino and Sierra Nevada temporary arrays. The t* data were used in Q inversions, using existing hypocenters and 3-D velocity models, with basic 10-km node spacing. The uneven data coverage was accounted for with linking of nodes into larger areas in order to provide useful Q images across the 3-D volume. The results at shallow depth (< 2 km) show very low Q in the Sacramento Delta, the Eureka area, and parts of the Bay Area. In the brittle crust, fault zones that have high seismicity exhibit low Q. In the lower crust, low Q is observed along fault zones that have large cumulative displacement and have experienced grain size reduction. Underlying active volcanic areas, low Q features are apparent below 20-km depth. Moderately high Q is associated with igneous rocks of the Sierra Nevada and Salinian block, while the Franciscan subduction complex shows moderately low Q. The most prominent high Q feature is related to the Great Valley Ophiolite.

  14. Effective 3-D surface modeling for geographic information systems

    NASA Astrophysics Data System (ADS)

    Yüksek, K.; Alparslan, M.; Mendi, E.

    2016-01-01

    In this work, we propose a dynamic, flexible and interactive urban digital terrain platform with spatial data and query processing capabilities of geographic information systems, multimedia database functionality and graphical modeling infrastructure. A new data element, called Geo-Node, which stores image, spatial data and 3-D CAD objects is developed using an efficient data structure. The system effectively handles data transfer of Geo-Nodes between main memory and secondary storage with an optimized directional replacement policy (DRP) based buffer management scheme. Polyhedron structures are used in digital surface modeling and smoothing process is performed by interpolation. The experimental results show that our framework achieves high performance and works effectively with urban scenes independent from the amount of spatial data and image size. The proposed platform may contribute to the development of various applications such as Web GIS systems based on 3-D graphics standards (e.g., X3-D and VRML) and services which integrate multi-dimensional spatial information and satellite/aerial imagery.

  15. Right approach to 3D modeling using CAD tools

    NASA Astrophysics Data System (ADS)

    Baddam, Mounica Reddy

    The thesis provides a step-by-step methodology to enable an instructor dealing with CAD tools to optimally guide his/her students through an understandable 3D modeling approach which will not only enhance their knowledge about the tool's usage but also enable them to achieve their desired result in comparatively lesser time. In the known practical field, there is particularly very little information available to apply CAD skills to formal beginners' training sessions. Additionally, advent of new software in 3D domain cumulates updating into a more difficult task. Keeping up to the industry's advanced requirements emphasizes the importance of more skilled hands in the field of CAD development, rather than just prioritizing manufacturing in terms of complex software features. The thesis analyses different 3D modeling approaches specified to the varieties of CAD tools currently available in the market. Utilizing performance-time databases, learning curves have been generated to measure their performance time, feature count etc. Based on the results, improvement parameters have also been provided for (Asperl, 2005).

  16. 3D-printer visualization of neuron models

    PubMed Central

    McDougal, Robert A.; Shepherd, Gordon M.

    2015-01-01

    Neurons come in a wide variety of shapes and sizes. In a quest to understand this neuronal diversity, researchers have three-dimensionally traced tens of thousands of neurons; many of these tracings are freely available through online repositories like NeuroMorpho.Org and ModelDB. Tracings can be visualized on the computer screen, used for statistical analysis of the properties of different cell types, used to simulate neuronal behavior, and more. We introduce the use of 3D printing as a technique for visualizing traced morphologies. Our method for generating printable versions of a cell or group of cells is to expand dendrite and axon diameters and then to transform the tracing into a 3D object with a neuronal surface generating algorithm like Constructive Tessellated Neuronal Geometry (CTNG). We show that 3D printed cells can be readily examined, manipulated, and compared with other neurons to gain insight into both the biology and the reconstruction process. We share our printable models in a new database, 3DModelDB, and encourage others to do the same with cells that they generate using our code or other methods. To provide additional context, 3DModelDB provides a simulatable version of each cell, links to papers that use or describe it, and links to associated entries in other databases. PMID:26175684

  17. 3D-printer visualization of neuron models.

    PubMed

    McDougal, Robert A; Shepherd, Gordon M

    2015-01-01

    Neurons come in a wide variety of shapes and sizes. In a quest to understand this neuronal diversity, researchers have three-dimensionally traced tens of thousands of neurons; many of these tracings are freely available through online repositories like NeuroMorpho.Org and ModelDB. Tracings can be visualized on the computer screen, used for statistical analysis of the properties of different cell types, used to simulate neuronal behavior, and more. We introduce the use of 3D printing as a technique for visualizing traced morphologies. Our method for generating printable versions of a cell or group of cells is to expand dendrite and axon diameters and then to transform the tracing into a 3D object with a neuronal surface generating algorithm like Constructive Tessellated Neuronal Geometry (CTNG). We show that 3D printed cells can be readily examined, manipulated, and compared with other neurons to gain insight into both the biology and the reconstruction process. We share our printable models in a new database, 3DModelDB, and encourage others to do the same with cells that they generate using our code or other methods. To provide additional context, 3DModelDB provides a simulatable version of each cell, links to papers that use or describe it, and links to associated entries in other databases.

  18. Assessment of machine learning reliability methods for quantifying the applicability domain of QSAR regression models.

    PubMed

    Toplak, Marko; Močnik, Rok; Polajnar, Matija; Bosnić, Zoran; Carlsson, Lars; Hasselgren, Catrin; Demšar, Janez; Boyer, Scott; Zupan, Blaž; Stålring, Jonna

    2014-02-24

    The vastness of chemical space and the relatively small coverage by experimental data recording molecular properties require us to identify subspaces, or domains, for which we can confidently apply QSAR models. The prediction of QSAR models in these domains is reliable, and potential subsequent investigations of such compounds would find that the predictions closely match the experimental values. Standard approaches in QSAR assume that predictions are more reliable for compounds that are "similar" to those in subspaces with denser experimental data. Here, we report on a study of an alternative set of techniques recently proposed in the machine learning community. These methods quantify prediction confidence through estimation of the prediction error at the point of interest. Our study includes 20 public QSAR data sets with continuous response and assesses the quality of 10 reliability scoring methods by observing their correlation with prediction error. We show that these new alternative approaches can outperform standard reliability scores that rely only on similarity to compounds in the training set. The results also indicate that the quality of reliability scoring methods is sensitive to data set characteristics and to the regression method used in QSAR. We demonstrate that at the cost of increased computational complexity these dependencies can be leveraged by integration of scores from various reliability estimation approaches. The reliability estimation techniques described in this paper have been implemented in an open source add-on package ( https://bitbucket.org/biolab/orange-reliability ) to the Orange data mining suite. PMID:24490838

  19. Underwater 3d Modeling: Image Enhancement and Point Cloud Filtering

    NASA Astrophysics Data System (ADS)

    Sarakinou, I.; Papadimitriou, K.; Georgoula, O.; Patias, P.

    2016-06-01

    This paper examines the results of image enhancement and point cloud filtering on the visual and geometric quality of 3D models for the representation of underwater features. Specifically it evaluates the combination of effects from the manual editing of images' radiometry (captured at shallow depths) and the selection of parameters for point cloud definition and mesh building (processed in 3D modeling software). Such datasets, are usually collected by divers, handled by scientists and used for geovisualization purposes. In the presented study, have been created 3D models from three sets of images (seafloor, part of a wreck and a small boat's wreck) captured at three different depths (3.5m, 10m and 14m respectively). Four models have been created from the first dataset (seafloor) in order to evaluate the results from the application of image enhancement techniques and point cloud filtering. The main process for this preliminary study included a) the definition of parameters for the point cloud filtering and the creation of a reference model, b) the radiometric editing of images, followed by the creation of three improved models and c) the assessment of results by comparing the visual and the geometric quality of improved models versus the reference one. Finally, the selected technique is tested on two other data sets in order to examine its appropriateness for different depths (at 10m and 14m) and different objects (part of a wreck and a small boat's wreck) in the context of an ongoing research in the Laboratory of Photogrammetry and Remote Sensing.

  20. 3D Geologic Model of the San Diego Area

    NASA Astrophysics Data System (ADS)

    Danskin, W. R.; Cromwell, G.; Glockhoff, C.; Martin, D.

    2015-12-01

    Prior geologic studies of the San Diego area, including northern Baja California, Mexico, focused on site investigations, characterization of rock formations, or earthquake hazards. No comprehensive, quantitative model characterizing the three-dimensional (3D) geology of the entire area has been developed. The lack of such a model limits understanding of large-scale processes, such as development of ancient landforms, and groundwater movement and availability. To evaluate these regional processes, the United States Geological Survey (USGS) conducted a study to better understand the geologic structure of the San Diego area. A cornerstone of this study is the installation and analysis of 77 wells at 12 multiple-depth monitoring-well sites. Geologic information from these wells was combined with lithologic data from 81 oil exploration wells and municipal and private water wells, gravity and seismic interpretations, and paleontological interpretations. These data were analyzed in conjunction with geologic maps and digital elevation models to develop a 3D geologic model of the San Diego area, in particular of the San Diego embayment. Existing interpretations of regional surficial geology, faulting, and tectonic history provided the framework for this model, which was refined by independent evaluation of subsurface geology. Geologic formations were simplified into five sedimentary units (Quaternary, Plio-Pleistocene, Oligocene, Eocene and Cretaceous ages), and one basal crystalline unit (primarily Cretaceous and Jurassic). Complex fault systems are represented in the model by ten fault strands that maintain overall displacement. The 3D geologic model corroborates existing geologic concepts of the San Diego area, refines the extent of subsurface geology, and allows users to holistically evaluate subsurface structures and regional hydrogeology.

  1. QSAR models for estimating properties of persistent organic pollutants required in evaluation of their environmental fate and risk.

    PubMed

    Sabljic, A

    2001-04-01

    The molecular connectivity indices (MCIs) have been successfully used for over 20 years in quantitative structure activity relationships (QSAR) modelling in various areas of physics, chemistry, biology, drug design, and environmental sciences. With this review, we hope to assist present and future QSAR practitioners to apply MCIs more wisely and more critically. First, we have described the methods of calculation and systematics of MCIs. This section should be helpful in rational selection of MCIs for QSAR modelling. Then we have presented our long-term experience in the application of MCIs through several characteristic and successful QSAR models for estimating partitioning and chromatographic properties of persistent organic pollutants (POPs). We have also analysed the trends in calculated MCIs and discussed their physical interpretation. In conclusion, several practical recommendations and warnings, based on our research experience, have been given for the application of MCIs in the QSAR modelling. PMID:11302582

  2. Subduction zone guided waves: 3D modelling and attenuation effects

    NASA Astrophysics Data System (ADS)

    Garth, T.; Rietbrock, A.

    2013-12-01

    Waveform modelling is an important tool for understanding complex seismic structures such as subduction zone waveguides. These structures are often simplified to 2D structures for modelling purposes to reduce computational costs. In the case of subduction zone waveguide affects, 2D models have shown that dispersed arrivals are caused by a low velocity waveguide, inferred to be subducted oceanic crust and/or hydrated outer rise normal faults. However, due to the 2D modelling limitations the inferred seismic properties such as velocity contrast and waveguide thickness are still debated. Here we test these limitations with full 3D waveform modelling. For waveguide effects to be observable the waveform must be accurately modelled to relatively high frequencies (> 2 Hz). This requires a small grid spacing due to the high seismic velocities present in subduction zones. A large area must be modelled as well due to the long propagation distances (400 - 600 km) of waves interacting with subduction zone waveguides. The combination of the large model area and small grid spacing required means that these simulations require a large amount of computational resources, only available at high performance computational centres like the UK National super computer HECTOR (used in this study). To minimize the cost of modelling for such a large area, the width of the model area perpendicular to the subduction trench (the y-direction) is made as small as possible. This reduces the overall volume of the 3D model domain. Therefore the wave field is simulated in a model ';corridor' of the subduction zone velocity structure. This introduces new potential sources of error particularly from grazing wave side reflections in the y-direction. Various dampening methods are explored to reduce these grazing side reflections, including perfectly matched layers (PML) and more traditional exponential dampening layers. Defining a corridor model allows waveguide affects to be modelled up to at least 2

  3. 3D flare particle model for ShipIR/NTCS

    NASA Astrophysics Data System (ADS)

    Ramaswamy, Srinivasan; Vaitekunas, David A.

    2016-05-01

    A key component in any soft-kill response to an incoming guided missile is the flare /chaff decoy used to distract or seduce the seeker homing system away from the naval platform. This paper describes a new 3D flare particle model in the naval threat countermeasure simulator (NTCS) of the NATO-standard ship signature model (ShipIR), which provides independent control over the size and radial distribution of its signature. The 3D particles of each flare sub-munition are modelled stochastically and rendered using OpenGL z-buffering, 2D projection, and alpha-blending to produce a unique and time varying signature. A sensitivity analysis on each input parameter provides the data and methods needed to synthesize a model from an IR measurement of a decoy. The new model also eliminated artifacts and deficiencies in our previous model which prevented reliable tracks from the adaptive track gate algorithm already presented by Ramaswamy and Vaitekunas (2015). A sequence of scenarios are used to test and demonstrate the new flare model during a missile engagement.

  4. Digital 3D Borobudur - Integration of 3D surveying and modeling techniques

    NASA Astrophysics Data System (ADS)

    Suwardhi, D.; Menna, F.; Remondino, F.; Hanke, K.; Akmalia, R.

    2015-08-01

    The Borobudur temple (Indonesia) is one of the greatest Buddhist monuments in the world, now listed as an UNESCO World Heritage Site. The present state of the temple is the result of restorations after being exposed to natural disasters several times. Today there is still a growing rate of deterioration of the building stones whose causes need further researches. Monitoring programs, supported at institutional level, have been effectively executed to observe the problem. The paper presents the latest efforts to digitally document the Borobudur Temple and its surrounding area in 3D with photogrammetric techniques. UAV and terrestrial images were acquired to completely digitize the temple, produce DEM, orthoimages and maps at 1:100 and 1:1000 scale. The results of the project are now employed by the local government organizations to manage the heritage area and plan new policies for the conservation and preservation of the UNESCO site. In order to help data management and policy makers, a web-based information system of the heritage area was also built to visualize and easily access all the data and achieved 3D results.

  5. Discrete Method of Images for 3D Radio Propagation Modeling

    NASA Astrophysics Data System (ADS)

    Novak, Roman

    2016-09-01

    Discretization by rasterization is introduced into the method of images (MI) in the context of 3D deterministic radio propagation modeling as a way to exploit spatial coherence of electromagnetic propagation for fine-grained parallelism. Traditional algebraic treatment of bounding regions and surfaces is replaced by computer graphics rendering of 3D reflections and double refractions while building the image tree. The visibility of reception points and surfaces is also resolved by shader programs. The proposed rasterization is shown to be of comparable run time to that of the fundamentally parallel shooting and bouncing rays. The rasterization does not affect the signal evaluation backtracking step, thus preserving its advantage over the brute force ray-tracing methods in terms of accuracy. Moreover, the rendering resolution may be scaled back for a given level of scenario detail with only marginal impact on the image tree size. This allows selection of scene optimized execution parameters for faster execution, giving the method a competitive edge. The proposed variant of MI can be run on any GPU that supports real-time 3D graphics.

  6. Consensus hologram QSAR modeling for the prediction of human intestinal absorption.

    PubMed

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications.

  7. A three-tier QSAR modeling strategy for estimating eye irritation potential of diverse chemicals in rabbit for regulatory purposes.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2016-06-01

    Experimental determination of the eye irritation potential (EIP) of chemicals is not only tedious, time and resource intensive, it involves cruelty to test animals. In this study, we have established a three-tier QSAR modeling strategy for estimating the EIP of chemicals for the use of pharmaceutical industry and regulatory agencies. Accordingly, a qualitative (binary classification: irritating, non-irritating), semi-quantitative (four-category classification), and quantitative (regression) QSAR models employing the SDT, DTF, and DTB methods were developed for predicting the EIP of chemicals in accordance with the OECD guidelines. Structural features of chemicals responsible for eye irritation were extracted and used in QSAR analysis. The external predictive power of the developed QSAR models were evaluated through the internal and external validation procedures recommended in QSAR literature. In test data, the two and four category classification QSAR models (DTF, DTB) rendered accuracy of >93%, while the regression QSAR models (DTF, DTB) yielded correlation (R(2)) of >0.92 between the measured and predicted EIPs. Values of various statistical validation coefficients derived for the test data were above their respective threshold limits (except rm(2) in DTF), thus put a high confidence in this analysis. The applicability domain of the constructed QSAR models were defined using the descriptors range and leverage approaches. The QSAR models in this study performed better than any of the previous studies. The results suggest that the developed QSAR models can reliably predict the EIP of diverse chemicals and can be useful tools for screening of candidate molecules in the drug development process.

  8. Modeling the GFR with RELAP5-3D

    SciTech Connect

    Cliff B. Davis; Theron D. Marshall; K. D. Weaver

    2005-09-01

    Significant improvements have been made to the RELAP5-3D computer code for analysis of the Gas Fast Reactor (GFR). These improvements consisted of adding carbon dioxide as a working fluid, improving the turbine component, developing a compressor model, and adding the Gnielinski heat transfer correlation. The code improvements were validated, generally through comparisons with independent design calculations. A model of the power conversion unit of the GFR was developed. The model of the power conversion unit was coupled to a reactor model to develop a complete model of the GFR system. The RELAP5 model of the GFR was used to simulate two transients, one initiated by a reactor trip and the other initiated by a loss of load.

  9. Testing Mercury Porosimetry with 3D Printed Porosity Models

    NASA Astrophysics Data System (ADS)

    Hasiuk, F.; Ewing, R. P.; Hu, Q.

    2014-12-01

    Mercury intrusion porosimetry is one of the most widely used techniques to study the porous nature of a geological and man-made materials. In the geosciences, it is commonly used to describe petroleum reservoir and seal rocks as well as to grade aggregates for the design of asphalt and portland cement concretes. It's wide utility stems from its ability to characterize a wide range of pore throat sizes (from nanometers to around a millimeter). The fundamental physical model underlying mercury intrusion porosimetry, the Washburn Equation, is based on the assumption that rock porosity can be described as a bundle of cylindrical tubes. 3D printing technology, also known as rapid prototyping, allows the construction of intricate and accurate models, exactly what is required to build models of rock porosity. We evaluate the applicability of the Washburn Equation by comparing properties (like porosity, pore and pore throat size distribution, and surface area) computed on digital porosity models (built from CT data, CAD designs, or periodic geometries) to properties measured via mercury intrusion porosimetry on 3D printed versions of the same digital porosity models.

  10. Simulation of AIMS measurements using rigorous mask 3D modeling

    NASA Astrophysics Data System (ADS)

    Chou, Chih-Shiang; Huang, Hsu-Ting; Chu, Fu-Sheng; Chu, Yuan-Chih; Huang, Wen-Chun; Liu, Ru-Gun; Gau, Tsai-Sheng

    2015-03-01

    Aerial image measurement system (AIMSTM) has been widely used for wafer level inspection of mask defects. Reported inspection flows include die-to-die (D2D) and die-to-database (D2DB) methods. For patterns that do not repeat in another die, only the D2DB approach is applicable. The D2DB method requires accurate simulation of AIMS measurements for a mask pattern. An optical vectorial model is needed to depict the mask diffraction effect in this simulation. To accurately simulate the imaging results, a rigorous electro-magnetic field (EMF) model is essential to correctly take account of the EMF scattering induced by the mask topography, which is usually called the mask 3D effect. In this study, the mask 3D model we use is rigorous coupled-wave analysis (RCWA), which calculates the diffraction fields from a single plane wave incidence. A hybrid Hopkins-Abbe method with RCWA is used to calculate the EMF diffraction at a desired accuracy level while keeping the computation time practical. We will compare the speed of the hybrid Hopkins-Abbe method to the rigorous Abbe method. The matching between simulation and experiment is more challenging for AIMS than CD-SEM because its measurements provide full intensity information. Parameters in the mask 3D model such as film stack thickness or film optical properties, is optimized during the fitting process. We will report the fitting results of AIMS images for twodimensional structures with various pitches. By accurately simulating the AIMS measurements, it provides a necessary tool to perform the mask inspection using the D2DB approach and to accurately predict the mask defects.

  11. Exploiting Textured 3D Models for Developing Serious Games

    NASA Astrophysics Data System (ADS)

    Kontogianni, G.; Georgopoulos, A.

    2015-08-01

    Digital technologies have affected significantly many fields of computer graphics such as Games and especially the field of the Serious Games. These games are usually used for educational proposes in many fields such as Health Care, Military applications, Education, Government etc. Especially Digital Cultural Heritage is a scientific area that Serious Games are applied and lately many applications appear in the related literature. Realistic 3D textured models which have been produced using different photogrammetric methods could be a useful tool for the creation of Serious Game applications in order to make the final result more realistic and close to the reality. The basic goal of this paper is how 3D textured models which are produced by photogrammetric methods can be useful for developing a more realistic environment of a Serious Game. The application of this project aims at the creation of an educational game for the Ancient Agora of Athens. The 3D models used vary not only as far as their production methods (i.e. Time of Flight laser scanner, Structure from Motion, Virtual historical reconstruction etc.) is concerned, but also as far as their era as some of them illustrated according to their existing situation and some others according to how these monuments looked like in the past. The Unity 3D® game developing environment was used for creating this application, in which all these models were inserted in the same file format. For the application two diachronic virtual tours of the Athenian Agora were produced. The first one illustrates the Agora as it is today and the second one at the 2nd century A.D. Finally the future perspective for the evolution of this game is presented which includes the addition of some questions that the user will be able to answer. Finally an evaluation is scheduled to be performed at the end of the project.

  12. 3D model tools for architecture and archaeology reconstruction

    NASA Astrophysics Data System (ADS)

    Vlad, Ioan; Herban, Ioan Sorin; Stoian, Mircea; Vilceanu, Clara-Beatrice

    2016-06-01

    The main objective of architectural and patrimonial survey is to provide a precise documentation of the status quo of the surveyed objects (monuments, buildings, archaeological object and sites) for preservation and protection, for scientific studies and restoration purposes, for the presentation to the general public. Cultural heritage documentation includes an interdisciplinary approach having as purpose an overall understanding of the object itself and an integration of the information which characterize it. The accuracy and the precision of the model are directly influenced by the quality of the measurements realized on field and by the quality of the software. The software is in the process of continuous development, which brings many improvements. On the other side, compared to aerial photogrammetry, close range photogrammetry and particularly architectural photogrammetry is not limited to vertical photographs with special cameras. The methodology of terrestrial photogrammetry has changed significantly and various photographic acquisitions are widely in use. In this context, the present paper brings forward a comparative study of TLS (Terrestrial Laser Scanner) and digital photogrammetry for 3D modeling. The authors take into account the accuracy of the 3D models obtained, the overall costs involved for each technology and method and the 4th dimension - time. The paper proves its applicability as photogrammetric technologies are nowadays used at a large scale for obtaining the 3D model of cultural heritage objects, efficacious in their assessment and monitoring, thus contributing to historic conservation. Its importance also lies in highlighting the advantages and disadvantages of each method used - very important issue for both the industrial and scientific segment when facing decisions such as in which technology to invest more research and funds.

  13. The Engelbourg's ruins: from 3D TLS point cloud acquisition to 3D virtual and historic models

    NASA Astrophysics Data System (ADS)

    Koehl, Mathieu; Berger, Solveig; Nobile, Sylvain

    2014-05-01

    The Castle of Engelbourg was built at the beginning of the 13th century, at the top of the Schlossberg. It is situated on the territory of the municipality of Thann (France), at the crossroads of Alsace and Lorraine, and dominates the outlet of the valley of Thur. Its strategic position was one of the causes of its systematic destructions during the 17th century, and Louis XIV finished his fate by ordering his demolition in 1673. Today only few vestiges remain, of which a section of the main tower from about 7m of diameter and 4m of wide laying on its slice, unique characteristic in the regional castral landscape. It is visible since the valley, was named "the Eye of the witch", and became a key attraction of the region. The site, which extends over approximately one hectare, is for several years the object of numerous archaeological studies and is at the heart of a project of valuation of the vestiges today. It was indeed a key objective, among the numerous planned works, to realize a 3D model of the site in its current state, in other words, a virtual model "such as seized", exploitable as well from a cultural and tourist point of view as by scientists and in archaeological researches. The team of the ICube/INSA lab had in responsibility the realization of this model, the acquisition of the data until the delivery of the virtual model, thanks to 3D TLS and topographic surveying methods. It was also planned to integrate into this 3D model, data of 2D archives, stemming from series of former excavations. The objectives of this project were the following ones: • Acquisition of 3D digital data of the site and 3D modelling • Digitization of the 2D archaeological data and integration in the 3D model • Implementation of a database connected to the 3D model • Virtual Visit of the site The obtained results allowed us to visualize every 3D object individually, under several forms (point clouds, 3D meshed objects and models, etc.) and at several levels of detail

  14. Discussion of Source Reconstruction Models Using 3D MCG Data

    NASA Astrophysics Data System (ADS)

    Melis, Massimo De; Uchikawa, Yoshinori

    In this study we performed the source reconstruction of magnetocardiographic signals generated by the human heart activity to localize the site of origin of the heart activation. The localizations were performed in a four compartment model of the human volume conductor. The analyses were conducted on normal subjects and on a subject affected by the Wolff-Parkinson-White syndrome. Different models of the source activation were used to evaluate whether a general model of the current source can be applied in the study of the cardiac inverse problem. The data analyses were repeated using normal and vector component data of the MCG. The results show that a distributed source model has the better accuracy in performing the source reconstructions, and that 3D MCG data allow finding smaller differences between the different source models.

  15. Modeling moving systems with RELAP5-3D

    DOE PAGES

    Mesina, G. L.; Aumiller, David L.; Buschman, Francis X.; Kyle, Matt R.

    2015-12-04

    RELAP5-3D is typically used to model stationary, land-based reactors. However, it can also model reactors in other inertial and accelerating frames of reference. By changing the magnitude of the gravitational vector through user input, RELAP5-3D can model reactors on a space station or the moon. The field equations have also been modified to model reactors in a non-inertial frame, such as occur in land-based reactors during earthquakes or onboard spacecraft. Transient body forces affect fluid flow in thermal-fluid machinery aboard accelerating crafts during rotational and translational accelerations. It is useful to express the equations of fluid motion in the acceleratingmore » frame of reference attached to the moving craft. However, careful treatment of the rotational and translational kinematics is required to accurately capture the physics of the fluid motion. Correlations for flow at angles between horizontal and vertical are generated via interpolation where no experimental studies or data exist. The equations for three-dimensional fluid motion in a non-inertial frame of reference are developed. As a result, two different systems for describing rotational motion are presented, user input is discussed, and an example is given.« less

  16. Modeling moving systems with RELAP5-3D

    SciTech Connect

    Mesina, G. L.; Aumiller, David L.; Buschman, Francis X.; Kyle, Matt R.

    2015-12-04

    RELAP5-3D is typically used to model stationary, land-based reactors. However, it can also model reactors in other inertial and accelerating frames of reference. By changing the magnitude of the gravitational vector through user input, RELAP5-3D can model reactors on a space station or the moon. The field equations have also been modified to model reactors in a non-inertial frame, such as occur in land-based reactors during earthquakes or onboard spacecraft. Transient body forces affect fluid flow in thermal-fluid machinery aboard accelerating crafts during rotational and translational accelerations. It is useful to express the equations of fluid motion in the accelerating frame of reference attached to the moving craft. However, careful treatment of the rotational and translational kinematics is required to accurately capture the physics of the fluid motion. Correlations for flow at angles between horizontal and vertical are generated via interpolation where no experimental studies or data exist. The equations for three-dimensional fluid motion in a non-inertial frame of reference are developed. As a result, two different systems for describing rotational motion are presented, user input is discussed, and an example is given.

  17. 3D multispecies collisional model of Ganymede's atmosphere

    NASA Astrophysics Data System (ADS)

    Leblanc, Francois; Leclercq, Ludivine; Oza, Apurva; Schmidt, Carl; Modolo, Ronan; Chaufray, Jean-Yves; Johnson, Robert E.

    2016-10-01

    Ganymede's atmosphere is produced by the interaction of the Sun and of the Jovian magnetosphere with its surface. It is a reflection of Ganymede's surface properties, but also of the complex interaction between the Ganymede and Jupiter magnetospheres. The Exospheric Global Model (EGM) has been developed in order to be able to integrate surface and magnetosphere processes with those in Ganymede's atmosphere. It is a 3D parallelized multi-species collisional model, coupled with LatHys, a hybrid multi-grid 3D multi-species model of Ganymede's magnetosphere (Leclercq et al., Geophys. Res. Let., Submitted, 2016). EGM's description of the species-dependent spatial distribution of Ganymede's atmosphere, its temporal variability during rotation around Jupiter, its connection to the surface, the role of collisions, and respective roles of sublimation and sputtering in producing Ganymede's exosphere, illustrates how modeling combined with in situ and remote sensing of Ganymede's atmosphere can contribute to our understanding of this unique surface-atmosphere-magnetosphere integrated system.

  18. Reassessing Geophysical Models of the Bushveld Complex in 3D

    NASA Astrophysics Data System (ADS)

    Cole, J.; Webb, S. J.; Finn, C.

    2012-12-01

    Conceptual geophysical models of the Bushveld Igneous Complex show three possible geometries for its mafic component: 1) Separate intrusions with vertical feeders for the eastern and western lobes (Cousins, 1959) 2) Separate dipping sheets for the two lobes (Du Plessis and Kleywegt, 1987) 3) A single saucer-shaped unit connected at depth in the central part between the two lobes (Cawthorn et al, 1998) Model three incorporates isostatic adjustment of the crust in response to the weight of the dense mafic material. The model was corroborated by results of a broadband seismic array over southern Africa, known as the Southern African Seismic Experiment (SASE) (Nguuri, et al, 2001; Webb et al, 2004). This new information about the crustal thickness only became available in the last decade and could not be considered in the earlier models. Nevertheless, there is still on-going debate as to which model is correct. All of the models published up to now have been done in 2 or 2.5 dimensions. This is not well suited to modelling the complex geometry of the Bushveld intrusion. 3D modelling takes into account effects of variations in geometry and geophysical properties of lithologies in a full three dimensional sense and therefore affects the shape and amplitude of calculated fields. The main question is how the new knowledge of the increased crustal thickness, as well as the complexity of the Bushveld Complex, will impact on the gravity fields calculated for the existing conceptual models, when modelling in 3D. The three published geophysical models were remodelled using full 3Dl potential field modelling software, and including crustal thickness obtained from the SASE. The aim was not to construct very detailed models, but to test the existing conceptual models in an equally conceptual way. Firstly a specific 2D model was recreated in 3D, without crustal thickening, to establish the difference between 2D and 3D results. Then the thicker crust was added. Including the less

  19. Building up a QSAR model for toxicity toward Tetrahymena pyriformis by the Monte Carlo method: A case of benzene derivatives.

    PubMed

    Toropova, Alla P; Schultz, Terry W; Toropov, Andrey A

    2016-03-01

    Data on toxicity toward Tetrahymena pyriformis is indicator of applicability of a substance in ecologic and pharmaceutical aspects. Quantitative structure-activity relationships (QSARs) between the molecular structure of benzene derivatives and toxicity toward T. pyriformis (expressed as the negative logarithms of the population growth inhibition dose, mmol/L) are established. The available data were randomly distributed three times into the visible training and calibration sets, and invisible validation sets. The statistical characteristics for the validation set are the following: r(2)=0.8179 and s=0.338 (first distribution); r(2)=0.8682 and s=0.341 (second distribution); r(2)=0.8435 and s=0.323 (third distribution). These models are built up using only information on the molecular structure: no data on physicochemical parameters, 3D features of the molecular structure and quantum mechanics descriptors are involved in the modeling process.

  20. Adaptive mesh refinement techniques for 3-D skin electrode modeling.

    PubMed

    Sawicki, Bartosz; Okoniewski, Michal

    2010-03-01

    In this paper, we develop a 3-D adaptive mesh refinement technique. The algorithm is constructed with an electric impedance tomography forward problem and the finite-element method in mind, but is applicable to a much wider class of problems. We use the method to evaluate the distribution of currents injected into a model of a human body through skin contact electrodes. We demonstrate that the technique leads to a significantly improved solution, particularly near the electrodes. We discuss error estimation, efficiency, and quality of the refinement algorithm and methods that allow for preserving mesh attributes in the refinement process.

  1. 3D simulation of the Cluster-Cluster Aggregation model

    NASA Astrophysics Data System (ADS)

    Li, Chao; Xiong, Hailing

    2014-12-01

    We write a program to implement the Cluster-Cluster Aggregation (CCA) model with java programming language. By using the simulation program, the fractal aggregation growth process can be displayed dynamically in the form of a three-dimensional (3D) figure. Meanwhile, the related kinetics data of aggregation simulation can be also recorded dynamically. Compared to the traditional programs, the program has better real-time performance and is more helpful to observe the fractal growth process, which contributes to the scientific study in fractal aggregation. Besides, because of adopting java programming language, the program has very good cross-platform performance.

  2. 3D in vitro cell culture models of tube formation.

    PubMed

    Zegers, Mirjam M

    2014-07-01

    Building the complex architecture of tubular organs is a highly dynamic process that involves cell migration, polarization, shape changes, adhesion to neighboring cells and the extracellular matrix, physicochemical characteristics of the extracellular matrix and reciprocal signaling with the mesenchyme. Understanding these processes in vivo has been challenging as they take place over extended time periods deep within the developing organism. Here, I will discuss 3D in vitro models that have been crucial to understand many of the molecular and cellular mechanisms and key concepts underlying branching morphogenesis in vivo. PMID:24613912

  3. A generic 3D kinetic model of gene expression

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.

    2012-04-01

    Recent experiments show that mRNAs and proteins can be localized both in prokaryotic and eukaryotic cells. To describe such situations, I present a 3D mean-field kinetic model aimed primarily at gene expression in prokaryotic cells, including the formation of mRNA, its translation into protein, and slow diffusion of these species. Under steady-state conditions, the mRNA and protein spatial distribution is described by simple exponential functions. The protein concentration near the gene transcribed into mRNA is shown to depend on the protein and mRNA diffusion coefficients and degradation rate constants.

  4. Developing Enhanced Blood–Brain Barrier Permeability Models: Integrating External Bio-Assay Data in QSAR Modeling

    PubMed Central

    Wang, Wenyi; Kim, Marlene T.; Sedykh, Alexander

    2015-01-01

    Purpose Experimental Blood–Brain Barrier (BBB) permeability models for drug molecules are expensive and time-consuming. As alternative methods, several traditional Quantitative Structure-Activity Relationship (QSAR) models have been developed previously. In this study, we aimed to improve the predictivity of traditional QSAR BBB permeability models by employing relevant public bio-assay data in the modeling process. Methods We compiled a BBB permeability database consisting of 439 unique compounds from various resources. The database was split into a modeling set of 341 compounds and a validation set of 98 compounds. Consensus QSAR modeling workflow was employed on the modeling set to develop various QSAR models. A five-fold cross-validation approach was used to validate the developed models, and the resulting models were used to predict the external validation set compounds. Furthermore, we used previously published membrane transporter models to generate relevant transporter profiles for target compounds. The transporter profiles were used as additional biological descriptors to develop hybrid QSAR BBB models. Results The consensus QSAR models have R2=0.638 for fivefold cross-validation and R2=0.504 for external validation. The consensus model developed by pooling chemical and transporter descriptors showed better predictivity (R2=0.646 for five-fold cross-validation and R2=0.526 for external validation). Moreover, several external bio-assays that correlate with BBB permeability were identified using our automatic profiling tool. Conclusions The BBB permeability models developed in this study can be useful for early evaluation of new compounds (e.g., new drug candidates). The combination of chemical and biological descriptors shows a promising direction to improve the current traditional QSAR models. PMID:25862462

  5. Does Rational Selection of Training and Test Sets Improve the Outcome of QSAR Modeling?

    EPA Science Inventory

    Prior to using a quantitative structure activity relationship (QSAR) model for external predictions, its predictive power should be established and validated. In the absence of a true external dataset, the best way to validate the predictive ability of a model is to perform its s...

  6. High Resolution 3d Numerical Modelling of Rockfalls

    NASA Astrophysics Data System (ADS)

    Agliardi, F.; Crosta, G. B.

    Accurate modelling of rockfall dynamics is a major issue for engineering geologists and land planners in rockfall prone areas, both for hazard assessment and the design of countermeasures. Numerical modelling of rockfalls has been generally performed in two dimensions. Thus, this is subjected to the crucial "a priori" choice of the rock- fall path and affected by a significant error due to the lateral dispersion of rockfall trajectories. In this study, an original 3D rockfall simulation program, first developed for regional scale distributed analysis, has been tested at a local scale with a very high spatial resolution, in order to show its performance in modelling site-specific prob- lems (runout definition, hazard assessment, design and verification of barriers). The code is based on a "lumped mass" kinematic algorithm allowing to simulate the free fall, impact-rebound and rolling motion of boulders on a three-dimensional topogra- phy described by a DTM. The code allows to run very detailed 3D simulations with almost no limitations in the number of modeled rockfall sources, slope elements and topographic points, using spatially distributed input data. Two case studies from the Mt. S.Martino area (Lecco, Larian Prealps) and the Gembrasca area (Valfurva, Central Alps), both from the mountainous area of the Lombardia Region (Northern Italy) are presented. Both the two examples are particularly intriguing because of the occurrence of well-known historical events (one of which causing fatalities) and the presence of valuable elements at risk (urban areas, transportation corridors) and defensive mea- sures (elasto-plastic barriers and catch walls). The Mt. S.Martino model is based on a DTM with cell size of 5 m, obtained from a 1:5.000 scale contour map, while the Gembrasca one uses an extremely detailed LIDAR-ALTM laser topography with a cell size of 1 m. The location of rockfall sources and the data used to develop and calibrate the two models have been collected

  7. Heralding a new paradigm in 3D tumor modeling.

    PubMed

    Fong, Eliza L S; Harrington, Daniel A; Farach-Carson, Mary C; Yu, Hanry

    2016-11-01

    Numerous studies to date have contributed to a paradigm shift in modeling cancer, moving from the traditional two-dimensional culture system to three-dimensional (3D) culture systems for cancer cell culture. This led to the inception of tumor engineering, which has undergone rapid advances over the years. In line with the recognition that tumors are not merely masses of proliferating cancer cells but rather, highly complex tissues consisting of a dynamic extracellular matrix together with stromal, immune and endothelial cells, significant efforts have been made to better recapitulate the tumor microenvironment in 3D. These approaches include the development of engineered matrices and co-cultures to replicate the complexity of tumor-stroma interactions in vitro. However, the tumor engineering and cancer biology fields have traditionally relied heavily on the use of cancer cell lines as a cell source in tumor modeling. While cancer cell lines have contributed to a wealth of knowledge in cancer biology, the use of this cell source is increasingly perceived as a major contributing factor to the dismal failure rate of oncology drugs in drug development. Backing this notion is the increasing evidence that tumors possess intrinsic heterogeneity, which predominantly homogeneous cancer cell lines poorly reflect. Tumor heterogeneity contributes to therapeutic resistance in patients. To overcome this limitation, cancer cell lines are beginning to be replaced by primary tumor cell sources, in the form of patient-derived xenografts and organoids cultures. Moving forward, we propose that further advances in tumor engineering would require that tumor heterogeneity (tumor variants) be taken into consideration together with tumor complexity (tumor-stroma interactions). In this review, we provide a comprehensive overview of what has been achieved in recapitulating tumor complexity, and discuss the importance of incorporating tumor heterogeneity into 3D in vitro tumor models. This

  8. A Prototype Digital Library for 3D Collections: Tools To Capture, Model, Analyze, and Query Complex 3D Data.

    ERIC Educational Resources Information Center

    Rowe, Jeremy; Razdan, Anshuman

    The Partnership for Research in Spatial Modeling (PRISM) project at Arizona State University (ASU) developed modeling and analytic tools to respond to the limitations of two-dimensional (2D) data representations perceived by affiliated discipline scientists, and to take advantage of the enhanced capabilities of three-dimensional (3D) data that…

  9. Canada in 3D - Toward a Sustainable 3D Model for Canadian Geology from Diverse Data Sources

    NASA Astrophysics Data System (ADS)

    Brodaric, B.; Pilkington, M.; Snyder, D. B.; St-Onge, M. R.; Russell, H.

    2015-12-01

    Many big science issues span large areas and require data from multiple heterogeneous sources, for example climate change, resource management, and hazard mitigation. Solutions to these issues can significantly benefit from access to a consistent and integrated geological model that would serve as a framework. However, such a model is absent for most large countries including Canada, due to the size of the landmass and the fragmentation of the source data into institutional and disciplinary silos. To overcome these barriers, the "Canada in 3D" (C3D) pilot project was recently launched by the Geological Survey of Canada. C3D is designed to be evergreen, multi-resolution, and inter-disciplinary: (a) it is to be updated regularly upon acquisition of new data; (b) portions vary in resolution and will initially consist of four layers (surficial, sedimentary, crystalline, and mantle) with intermediary patches of higher-resolution fill; and (c) a variety of independently managed data sources are providing inputs, such as geophysical, 3D and 2D geological models, drill logs, and others. Notably, scalability concerns dictate a decentralized and interoperable approach, such that only key control objects, denoting anchors for the modeling process, are imported into the C3D database while retaining provenance links to original sources. The resultant model is managed in the database, contains full modeling provenance as well as links to detailed information on rock units, and is to be visualized in desktop and online environments. It is anticipated that C3D will become the authoritative state of knowledge for the geology of Canada at a national scale.

  10. Antibacterial Activity of Imidazolium-Based Ionic Liquids Investigated by QSAR Modeling and Experimental Studies.

    PubMed

    Hodyna, Diana; Kovalishyn, Vasyl; Rogalsky, Sergiy; Blagodatnyi, Volodymyr; Petko, Kirill; Metelytsia, Larisa

    2016-09-01

    Predictive QSAR models for the inhibitors of B. subtilis and Ps. aeruginosa among imidazolium-based ionic liquids were developed using literary data. The regression QSAR models were created through Artificial Neural Network and k-nearest neighbor procedures. The classification QSAR models were constructed using WEKA-RF (random forest) method. The predictive ability of the models was tested by fivefold cross-validation; giving q(2) = 0.77-0.92 for regression models and accuracy 83-88% for classification models. Twenty synthesized samples of 1,3-dialkylimidazolium ionic liquids with predictive value of activity level of antimicrobial potential were evaluated. For all asymmetric 1,3-dialkylimidazolium ionic liquids, only compounds containing at least one radical with alkyl chain length of 12 carbon atoms showed high antibacterial activity. However, the activity of symmetric 1,3-dialkylimidazolium salts was found to have opposite relationship with the length of aliphatic radical being maximum for compounds based on 1,3-dioctylimidazolium cation. The obtained experimental results suggested that the application of classification QSAR models is more accurate for the prediction of activity of new imidazolium-based ILs as potential antibacterials. PMID:27086199

  11. Comparative 3-D Modeling of tmRNA

    PubMed Central

    Burks, Jody; Zwieb, Christian; Müller, Florian; Wower, Iwona; Wower, Jacek

    2005-01-01

    Background Trans-translation releases stalled ribosomes from truncated mRNAs and tags defective proteins for proteolytic degradation using transfer-messenger RNA (tmRNA). This small stable RNA represents a hybrid of tRNA- and mRNA-like domains connected by a variable number of pseudoknots. Comparative sequence analysis of tmRNAs found in bacteria, plastids, and mitochondria provides considerable insights into their secondary structures. Progress toward understanding the molecular mechanism of template switching, which constitutes an essential step in trans-translation, is hampered by our limited knowledge about the three-dimensional folding of tmRNA. Results To facilitate experimental testing of the molecular intricacies of trans-translation, which often require appropriately modified tmRNA derivatives, we developed a procedure for building three-dimensional models of tmRNA. Using comparative sequence analysis, phylogenetically-supported 2-D structures were obtained to serve as input for the program ERNA-3D. Motifs containing loops and turns were extracted from the known structures of other RNAs and used to improve the tmRNA models. Biologically feasible 3-D models for the entire tmRNA molecule could be obtained. The models were characterized by a functionally significant close proximity between the tRNA-like domain and the resume codon. Potential conformational changes which might lead to a more open structure of tmRNA upon binding to the ribosome are discussed. The method, described in detail for the tmRNAs of Escherichia coli, Bacillus anthracis, and Caulobacter crescentus, is applicable to every tmRNA. Conclusion Improved molecular models of biological significance were obtained. These models will guide in the design of experiments and provide a better understanding of trans-translation. The comparative procedure described here for tmRNA is easily adopted for the modeling the members of other RNA families. PMID:15958166

  12. Inverse rendering of faces with a 3D morphable model.

    PubMed

    Aldrian, Oswald; Smith, William A P

    2013-05-01

    In this paper, we present a complete framework to inverse render faces with a 3D Morphable Model (3DMM). By decomposing the image formation process into geometric and photometric parts, we are able to state the problem as a multilinear system which can be solved accurately and efficiently. As we treat each contribution as independent, the objective function is convex in the parameters and a global solution is guaranteed. We start by recovering 3D shape using a novel algorithm which incorporates generalization error of the model obtained from empirical measurements. We then describe two methods to recover facial texture, diffuse lighting, specular reflectance, and camera properties from a single image. The methods make increasingly weak assumptions and can be solved in a linear fashion. We evaluate our findings on a publicly available database, where we are able to outperform an existing state-of-the-art algorithm. We demonstrate the usability of the recovered parameters in a recognition experiment conducted on the CMU-PIE database. PMID:23520253

  13. QSARINS-chem: Insubria datasets and new QSAR/QSPR models for environmental pollutants in QSARINS.

    PubMed

    Gramatica, Paola; Cassani, Stefano; Chirico, Nicola

    2014-05-15

    A database of environmentally hazardous chemicals, collected and modeled by QSAR by the Insubria group, is included in the updated version of QSARINS, software recently proposed for the development and validation of QSAR models by the genetic algorithm-ordinary least squares method. In this version, a module, named QSARINS-Chem, includes several datasets of chemical structures and their corresponding endpoints (physicochemical properties and biological activities). The chemicals are accessible in different ways (CAS, SMILES, names and so forth) and their three-dimensional structure can be visualized. Some of the QSAR models, previously published by our group, have been redeveloped using the free online software for molecular descriptor calculation, PaDEL-Descriptor. The new models can be easily applied for future predictions on chemicals without experimental data, also verifying the applicability domain to new chemicals. The QSAR model reporting format (QMRF) of these models is also here downloadable. Additional chemometric analyses can be done by principal component analysis and multicriteria decision making for screening and ranking chemicals to prioritize the most dangerous.

  14. Dynamic deformable models for 3D MRI heart segmentation

    NASA Astrophysics Data System (ADS)

    Zhukov, Leonid; Bao, Zhaosheng; Gusikov, Igor; Wood, John; Breen, David E.

    2002-05-01

    Automated or semiautomated segmentation of medical images decreases interstudy variation, observer bias, and postprocessing time as well as providing clincally-relevant quantitative data. In this paper we present a new dynamic deformable modeling approach to 3D segmentation. It utilizes recently developed dynamic remeshing techniques and curvature estimation methods to produce high-quality meshes. The approach has been implemented in an interactive environment that allows a user to specify an initial model and identify key features in the data. These features act as hard constraints that the model must not pass through as it deforms. We have employed the method to perform semi-automatic segmentation of heart structures from cine MRI data.

  15. Stochastic Modeling of Calcium in 3D Geometry

    PubMed Central

    Mazel, Tomáš; Raymond, Rebecca; Raymond-Stintz, Mary; Jett, Stephen; Wilson, Bridget S.

    2009-01-01

    Release of inflammatory mediators by mast cells in type 1 immediate-hypersensitivity allergic reactions relies on antigen-dependent increases in cytosolic calcium. Here, we used a series of electron microscopy images to build a 3D reconstruction representing a slice through a rat tumor mast cell, which then served as a basis for stochastic modeling of inositol-trisphosphate-mediated calcium responses. The stochastic approach was verified by reaction-diffusion modeling within the same geometry. Local proximity of the endoplasmic reticulum to either the plasma membrane or mitochondria is predicted to differentially impact local inositol trisphosphate receptor transport. The explicit consideration of organelle spatial relationships represents an important step toward building a comprehensive, realistic model of cellular calcium dynamics. PMID:19254531

  16. 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

  17. Topological order in an exactly solvable 3D spin model

    SciTech Connect

    Bravyi, Sergey; Leemhuis, Bernhard; Terhal, Barbara M.

    2011-04-15

    Research highlights: RHtriangle We study exactly solvable spin model with six-qubit nearest neighbor interactions on a 3D face centered cubic lattice. RHtriangle The ground space of the model exhibits topological quantum order. RHtriangle Elementary excitations can be geometrically described as the corners of rectangular-shaped membranes. RHtriangle The ground space can encode 4g qubits where g is the greatest common divisor of the lattice dimensions. RHtriangle Logical operators acting on the encoded qubits are described in terms of closed strings and closed membranes. - Abstract: We study a 3D generalization of the toric code model introduced recently by Chamon. This is an exactly solvable spin model with six-qubit nearest-neighbor interactions on an FCC lattice whose ground space exhibits topological quantum order. The elementary excitations of this model which we call monopoles can be geometrically described as the corners of rectangular-shaped membranes. We prove that the creation of an isolated monopole separated from other monopoles by a distance R requires an operator acting on {Omega}(R{sup 2}) qubits. Composite particles that consist of two monopoles (dipoles) and four monopoles (quadrupoles) can be described as end-points of strings. The peculiar feature of the model is that dipole-type strings are rigid, that is, such strings must be aligned with face-diagonals of the lattice. For periodic boundary conditions the ground space can encode 4g qubits where g is the greatest common divisor of the lattice dimensions. We describe a complete set of logical operators acting on the encoded qubits in terms of closed strings and closed membranes.

  18. In Silico Study of In Vitro GPCR Assays by QSAR Modeling.

    PubMed

    Mansouri, Kamel; Judson, Richard S

    2016-01-01

    The US EPA's ToxCast program is screening thousands of chemicals of environmental interest in hundreds of in vitro high-throughput screening (HTS) assays. One goal is to prioritize chemicals for more detailed analyses based on activity in assays that target molecular initiating events (MIEs) of adverse outcome pathways (AOPs). However, the chemical space of interest for environmental exposure is much wider than ToxCast's chemical library. In silico methods such as quantitative structure-activity relationships (QSARs) are proven and cost-effective approaches to predict biological activity for untested chemicals. However, empirical data is needed to build and validate QSARs. ToxCast has developed datasets for about 2000 chemicals ideal for training and testing QSAR models. The overall goal of the present work was to develop QSAR models to fill the data gaps in larger environmental chemical lists. The specific aim of the current work was to build QSAR models for 18 G-protein-coupled receptor (GPCR) assays, part of the aminergic family. Two QSAR modeling strategies were adopted: classification models were developed to separate chemicals into active/non-active classes, and then regression models were built to predict the potency values of the bioassays for the active chemicals. Multiple software programs were used to calculate constitutional, topological, and substructural molecular descriptors from two-dimensional (2D) chemical structures. Model-fitting methods included PLSDA (partial least square discriminant analysis), SVMs (support vector machines), kNNs (k-nearest neighbors), and PLSs (partial least squares). Genetic algorithms (GAs) were applied as a variable selection technique to select the most predictive molecular descriptors for each assay. N-fold cross-validation (CV) coupled with multi-criteria decision-making fitting criteria was used to evaluate the models. Finally, the models were applied to make predictions within the established chemical space limits

  19. Development of an aquifer management model AQMAN3D

    USGS Publications Warehouse

    Puig, Juan Carlos; Rolon-Collazo, L. I.; Pagan-Trinidad, Ishmael; Krishna, J.H.; Quinones-Aponte, Vicente; Gomez-Gomez, Fernando; Morris, G.L.

    1990-01-01

    A computer code that enables the use of the USGS Modular groundwater flow model for aquifermanagement modeling has been developed. Aquifermanagement techniques integrate groundwater flow modeling with linear quadratic optimization methods for the solution of various aquifer management problems. The model AQMAN3D, is a modified version of a previously developed two-dimensional AQMAN model. The idea of coupling the AQMAN model with the MODULAR model arose because actual groundwater flow systems behave in a three dimensional manner, therefore requiring treatment as such, and due to the widespread use of MODULAR. The use of the AQMAN3D model permits the implementation of the technique known as aquifer managementmodeling. A generalized approach to obtain an optimal solution to an aquifer management problem is proposed, and a sample test problem is presented to illustrate the use of the model. Even though the model provides the hydrologist with a new and powerful investigative tool, its applicability is limited to confined or quasiconfined systems.

  20. Quantitative structure-activity relationship (QSAR) for insecticides: development of predictive in vivo insecticide activity models.

    PubMed

    Naik, P K; Singh, T; Singh, H

    2009-07-01

    Quantitative structure-activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r(2) values of 0.949 and 0.838 as well as [image omitted] values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD(50) values for the test set data with r(2) of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.

  1. Geographic Video 3d Data Model And Retrieval

    NASA Astrophysics Data System (ADS)

    Han, Z.; Cui, C.; Kong, Y.; Wu, H.

    2014-04-01

    Geographic video includes both spatial and temporal geographic features acquired through ground-based or non-ground-based cameras. With the popularity of video capture devices such as smartphones, the volume of user-generated geographic video clips has grown significantly and the trend of this growth is quickly accelerating. Such a massive and increasing volume poses a major challenge to efficient video management and query. Most of the today's video management and query techniques are based on signal level content extraction. They are not able to fully utilize the geographic information of the videos. This paper aimed to introduce a geographic video 3D data model based on spatial information. The main idea of the model is to utilize the location, trajectory and azimuth information acquired by sensors such as GPS receivers and 3D electronic compasses in conjunction with video contents. The raw spatial information is synthesized to point, line, polygon and solid according to the camcorder parameters such as focal length and angle of view. With the video segment and video frame, we defined the three categories geometry object using the geometry model of OGC Simple Features Specification for SQL. We can query video through computing the spatial relation between query objects and three categories geometry object such as VFLocation, VSTrajectory, VSFOView and VFFovCone etc. We designed the query methods using the structured query language (SQL) in detail. The experiment indicate that the model is a multiple objective, integration, loosely coupled, flexible and extensible data model for the management of geographic stereo video.

  2. Nonlinear QSAR modeling for predicting cytotoxicity of ionic liquids in leukemia rat cell line: an aid to green chemicals designing.

    PubMed

    Gupta, Shikha; Basant, Nikita; Singh, Kunwar P

    2015-08-01

    Safety assessment and designing of safer ionic liquids (ILs) are among the priorities of the chemists and toxicologists today. Computational approaches have been considered as appropriate methods for prior safety assessment of chemicals and tools to aid in structural designing. The present study is an attempt to investigate the chemical attributes of a wide variety of ILs towards their cytotoxicity in leukemia rat cell line IPC-81 through the development of nonlinear quantitative structure-activity relationship (QSAR) models in the light of the OECD principles for QSAR development. Here, the cascade correlation network (CCN), probabilistic neural network (PNN), and generalized regression neural networks (GRNN) QSAR models were established for the discrimination of ILs in four categories of cytotoxicity and their end-point prediction using few simple descriptors. The diversity and nonlinearity of the considered dataset were evaluated through computing the Euclidean distance and Brock-Dechert-Scheinkman statistics. The constructed QSAR models were validated with external test data. The predictive power of these models was established through a variety of stringent parameters recommended in QSAR literature. The classification QSARs rendered the accuracy of >86%, and the regression models yielded correlation (R(2)) of >0.90 in test data. The developed QSAR models exhibited high statistical confidence and identified the structural elements of the ILs responsible for their cytotoxicity and, hence, could be useful tools in structural designing of safer and green ILs.

  3. Active Exploration of Large 3D Model Repositories.

    PubMed

    Gao, Lin; Cao, Yan-Pei; Lai, Yu-Kun; Huang, Hao-Zhi; Kobbelt, Leif; Hu, Shi-Min

    2015-12-01

    With broader availability of large-scale 3D model repositories, the need for efficient and effective exploration becomes more and more urgent. Existing model retrieval techniques do not scale well with the size of the database since often a large number of very similar objects are returned for a query, and the possibilities to refine the search are quite limited. We propose an interactive approach where the user feeds an active learning procedure by labeling either entire models or parts of them as "like" or "dislike" such that the system can automatically update an active set of recommended models. To provide an intuitive user interface, candidate models are presented based on their estimated relevance for the current query. From the methodological point of view, our main contribution is to exploit not only the similarity between a query and the database models but also the similarities among the database models themselves. We achieve this by an offline pre-processing stage, where global and local shape descriptors are computed for each model and a sparse distance metric is derived that can be evaluated efficiently even for very large databases. We demonstrate the effectiveness of our method by interactively exploring a repository containing over 100 K models. PMID:26529460

  4. 3D in vitro modeling of the central nervous system.

    PubMed

    Hopkins, Amy M; DeSimone, Elise; Chwalek, Karolina; Kaplan, David L

    2015-02-01

    There are currently more than 600 diseases characterized as affecting the central nervous system (CNS) which inflict neural damage. Unfortunately, few of these conditions have effective treatments available. Although significant efforts have been put into developing new therapeutics, drugs which were promising in the developmental phase have high attrition rates in late stage clinical trials. These failures could be circumvented if current 2D in vitro and in vivo models were improved. 3D, tissue-engineered in vitro systems can address this need and enhance clinical translation through two approaches: (1) bottom-up, and (2) top-down (developmental/regenerative) strategies to reproduce the structure and function of human tissues. Critical challenges remain including biomaterials capable of matching the mechanical properties and extracellular matrix (ECM) composition of neural tissues, compartmentalized scaffolds that support heterogeneous tissue architectures reflective of brain organization and structure, and robust functional assays for in vitro tissue validation. The unique design parameters defined by the complex physiology of the CNS for construction and validation of 3D in vitro neural systems are reviewed here.

  5. 3D in vitro modeling of the central nervous system

    PubMed Central

    Hopkins, Amy M.; DeSimone, Elise; Chwalek, Karolina; Kaplan, David L.

    2015-01-01

    There are currently more than 600 diseases characterized as affecting the central nervous system (CNS) which inflict neural damage. Unfortunately, few of these conditions have effective treatments available. Although significant efforts have been put into developing new therapeutics, drugs which were promising in the developmental phase have high attrition rates in late stage clinical trials. These failures could be circumvented if current 2D in vitro and in vivo models were improved. 3D, tissue-engineered in vitro systems can address this need and enhance clinical translation through two approaches: (1) bottom-up, and (2) top-down (developmental/regenerative) strategies to reproduce the structure and function of human tissues. Critical challenges remain including biomaterials capable of matching the mechanical properties and extracellular matrix (ECM) composition of neural tissues, compartmentalized scaffolds that support heterogeneous tissue architectures reflective of brain organization and structure, and robust functional assays for in vitro tissue validation. The unique design parameters defined by the complex physiology of the CNS for construction and validation of 3D in vitro neural systems are reviewed here. PMID:25461688

  6. Gene3D: modelling protein structure, function and evolution.

    PubMed

    Yeats, Corin; Maibaum, Michael; Marsden, Russell; Dibley, Mark; Lee, David; Addou, Sarah; Orengo, Christine A

    2006-01-01

    The Gene3D release 4 database and web portal (http://cathwww.biochem.ucl.ac.uk:8080/Gene3D) provide a combined structural, functional and evolutionary view of the protein world. It is focussed on providing structural annotation for protein sequences without structural representatives--including the complete proteome sets of over 240 different species. The protein sequences have also been clustered into whole-chain families so as to aid functional prediction. The structural annotation is generated using HMM models based on the CATH domain families; CATH is a repository for manually deduced protein domains. Amongst the changes from the last publication are: the addition of over 100 genomes and the UniProt sequence database, domain data from Pfam, metabolic pathway and functional data from COGs, KEGG and GO, and protein-protein interaction data from MINT and BIND. The website has been rebuilt to allow more sophisticated querying and the data returned is presented in a clearer format with greater functionality. Furthermore, all data can be downloaded in a simple XML format, allowing users to carry out complex investigations at their own computers.

  7. Modeling tree crown dynamics with 3D partial differential equations.

    PubMed

    Beyer, Robert; Letort, Véronique; Cournède, Paul-Henry

    2014-01-01

    We characterize a tree's spatial foliage distribution by the local leaf area density. Considering this spatially continuous variable allows to describe the spatiotemporal evolution of the tree crown by means of 3D partial differential equations. These offer a framework to rigorously take locally and adaptively acting effects into account, notably the growth toward light. Biomass production through photosynthesis and the allocation to foliage and wood are readily included in this model framework. The system of equations stands out due to its inherent dynamic property of self-organization and spontaneous adaptation, generating complex behavior from even only a few parameters. The density-based approach yields spatially structured tree crowns without relying on detailed geometry. We present the methodological fundamentals of such a modeling approach and discuss further prospects and applications. PMID:25101095

  8. Modeling tree crown dynamics with 3D partial differential equations.

    PubMed

    Beyer, Robert; Letort, Véronique; Cournède, Paul-Henry

    2014-01-01

    We characterize a tree's spatial foliage distribution by the local leaf area density. Considering this spatially continuous variable allows to describe the spatiotemporal evolution of the tree crown by means of 3D partial differential equations. These offer a framework to rigorously take locally and adaptively acting effects into account, notably the growth toward light. Biomass production through photosynthesis and the allocation to foliage and wood are readily included in this model framework. The system of equations stands out due to its inherent dynamic property of self-organization and spontaneous adaptation, generating complex behavior from even only a few parameters. The density-based approach yields spatially structured tree crowns without relying on detailed geometry. We present the methodological fundamentals of such a modeling approach and discuss further prospects and applications.

  9. Polygonal Shapes Detection in 3d Models of Complex Architectures

    NASA Astrophysics Data System (ADS)

    Benciolini, G. B.; Vitti, A.

    2015-02-01

    A sequential application of two global models defined on a variational framework is proposed for the detection of polygonal shapes in 3D models of complex architectures. As a first step, the procedure involves the use of the Mumford and Shah (1989) 1st-order variational model in dimension two (gridded height data are processed). In the Mumford-Shah model an auxiliary function detects the sharp changes, i.e., the discontinuities, of a piecewise smooth approximation of the data. The Mumford-Shah model requires the global minimization of a specific functional to simultaneously produce both the smooth approximation and its discontinuities. In the proposed procedure, the edges of the smooth approximation derived by a specific processing of the auxiliary function are then processed using the Blake and Zisserman (1987) 2nd-order variational model in dimension one (edges are processed in the plane). This second step permits to describe the edges of an object by means of piecewise almost-linear approximation of the input edges themselves and to detects sharp changes of the first-derivative of the edges so to detect corners. The Mumford-Shah variational model is used in two dimensions accepting the original data as primary input. The Blake-Zisserman variational model is used in one dimension for the refinement of the description of the edges. The selection among all the boundaries detected by the Mumford-Shah model of those that present a shape close to a polygon is performed by considering only those boundaries for which the Blake-Zisserman model identified discontinuities in their first derivative. The output of the procedure are hence shapes, coming from 3D geometric data, that can be considered as polygons. The application of the procedure is suitable for, but not limited to, the detection of objects such as foot-print of polygonal buildings, building facade boundaries or windows contours. v The procedure is applied to a height model of the building of the Engineering

  10. Advanced prior modeling for 3D bright field electron tomography

    NASA Astrophysics Data System (ADS)

    Sreehari, Suhas; Venkatakrishnan, S. V.; Drummy, Lawrence F.; Simmons, Jeffrey P.; Bouman, Charles A.

    2015-03-01

    Many important imaging problems in material science involve reconstruction of images containing repetitive non-local structures. Model-based iterative reconstruction (MBIR) could in principle exploit such redundancies through the selection of a log prior probability term. However, in practice, determining such a log prior term that accounts for the similarity between distant structures in the image is quite challenging. Much progress has been made in the development of denoising algorithms like non-local means and BM3D, and these are known to successfully capture non-local redundancies in images. But the fact that these denoising operations are not explicitly formulated as cost functions makes it unclear as to how to incorporate them in the MBIR framework. In this paper, we formulate a solution to bright field electron tomography by augmenting the existing bright field MBIR method to incorporate any non-local denoising operator as a prior model. We accomplish this using a framework we call plug-and-play priors that decouples the log likelihood and the log prior probability terms in the MBIR cost function. We specifically use 3D non-local means (NLM) as the prior model in the plug-and-play framework, and showcase high quality tomographic reconstructions of a simulated aluminum spheres dataset, and two real datasets of aluminum spheres and ferritin structures. We observe that streak and smear artifacts are visibly suppressed, and that edges are preserved. Also, we report lower RMSE values compared to the conventional MBIR reconstruction using qGGMRF as the prior model.

  11. Constructing and Validating 3D-pharmacophore Models to a Set of MMP-9 Inhibitors for Designing Novel Anti-melanoma Agents.

    PubMed

    Medeiros Turra, Kely; Pineda Rivelli, Diogo; Berlanga de Moraes Barros, Silvia; Mesquita Pasqualoto, Kerly Fernanda

    2016-07-01

    A receptor-independent (RI) four-dimensional structure-activity relationship (4D-QSAR) formalism was applied to a set of sixty-four β-N-biaryl ether sulfonamide hydroxamate derivatives, previously reported as potent inhibitors against matrix metalloproteinase subtype 9 (MMP-9). MMP-9 belongs to a group of enzymes related to the cleavage of several extracellular matrix components and has been associated to cancer invasiveness/metastasis. The best RI 4D-QSAR model was statistically significant (N=47; r(2) =0.91; q(2) =0.83; LSE=0.09; LOF=0.35; outliers=0). Leave-N-out (LNO) and y-randomization approaches indicated the QSAR model was robust and presented no chance correlation, respectively. Furthermore, it also had good external predictability (82 %) regarding the test set (N=17). In addition, the grid cell occupancy descriptors (GCOD) of the predicted bioactive conformation for the most potent inhibitor were successfully interpreted when docked into the MMP-9 active site. The 3D-pharmacophore findings were used to predict novel ligands and exploit the MMP-9 calculated binding affinity through molecular docking procedure. PMID:27492238

  12. Brandenburg 3D - a comprehensive 3D Subsurface Model, Conception of an Infrastructure Node and a Web Application

    NASA Astrophysics Data System (ADS)

    Kerschke, Dorit; Schilling, Maik; Simon, Andreas; Wächter, Joachim

    2014-05-01

    The Energiewende and the increasing scarcity of raw materials will lead to an intensified utilization of the subsurface in Germany. Within this context, geological 3D modeling is a fundamental approach for integrated decision and planning processes. Initiated by the development of the European Geospatial Infrastructure INSPIRE, the German State Geological Offices started digitizing their predominantly analog archive inventory. Until now, a comprehensive 3D subsurface model of Brandenburg did not exist. Therefore the project B3D strived to develop a new 3D model as well as a subsequent infrastructure node to integrate all geological and spatial data within the Geodaten-Infrastruktur Brandenburg (Geospatial Infrastructure, GDI-BB) and provide it to the public through an interactive 2D/3D web application. The functionality of the web application is based on a client-server architecture. Server-sided, all available spatial data is published through GeoServer. GeoServer is designed for interoperability and acts as the reference implementation of the Open Geospatial Consortium (OGC) Web Feature Service (WFS) standard that provides the interface that allows requests for geographical features. In addition, GeoServer implements, among others, the high performance certified compliant Web Map Service (WMS) that serves geo-referenced map images. For publishing 3D data, the OGC Web 3D Service (W3DS), a portrayal service for three-dimensional geo-data, is used. The W3DS displays elements representing the geometry, appearance, and behavior of geographic objects. On the client side, the web application is solely based on Free and Open Source Software and leans on the JavaScript API WebGL that allows the interactive rendering of 2D and 3D graphics by means of GPU accelerated usage of physics and image processing as part of the web page canvas without the use of plug-ins. WebGL is supported by most web browsers (e.g., Google Chrome, Mozilla Firefox, Safari, and Opera). The web

  13. Faceless identification: a model for person identification using the 3D shape and 3D motion as cues

    NASA Astrophysics Data System (ADS)

    Klasen, Lena M.; Li, Haibo

    1999-02-01

    Person identification by using biometric methods based on image sequences, or still images, often requires a controllable and cooperative environment during the image capturing stage. In the forensic case the situation is more likely to be the opposite. In this work we propose a method that makes use of the anthropometry of the human body and human actions as cues for identification. Image sequences from surveillance systems are used, which can be seen as monocular image sequences. A 3D deformable wireframe body model is used as a platform to handle the non-rigid information of the 3D shape and 3D motion of the human body from the image sequence. A recursive method for estimating global motion and local shape variations is presented, using two recursive feedback systems.

  14. Inferring multi-target QSAR models with taxonomy-based multi-task learning

    PubMed Central

    2013-01-01

    Background A plethora of studies indicate that the development of multi-target drugs is beneficial for complex diseases like cancer. Accurate QSAR models for each of the desired targets assist the optimization of a lead candidate by the prediction of affinity profiles. Often, the targets of a multi-target drug are sufficiently similar such that, in principle, knowledge can be transferred between the QSAR models to improve the model accuracy. In this study, we present two different multi-task algorithms from the field of transfer learning that can exploit the similarity between several targets to transfer knowledge between the target specific QSAR models. Results We evaluated the two methods on simulated data and a data set of 112 human kinases assembled from the public database ChEMBL. The relatedness between the kinase targets was derived from the taxonomy of the humane kinome. The experiments show that multi-task learning increases the performance compared to training separate models on both types of data given a sufficient similarity between the tasks. On the kinase data, the best multi-task approach improved the mean squared error of the QSAR models of 58 kinase targets. Conclusions Multi-task learning is a valuable approach for inferring multi-target QSAR models for lead optimization. The application of multi-task learning is most beneficial if knowledge can be transferred from a similar task with a lot of in-domain knowledge to a task with little in-domain knowledge. Furthermore, the benefit increases with a decreasing overlap between the chemical space spanned by the tasks. PMID:23842210

  15. Validation of a 3-D hemispheric nested air pollution model

    NASA Astrophysics Data System (ADS)

    Frohn, L. M.; Christensen, J. H.; Brandt, J.; Geels, C.; Hansen, K. M.

    2003-07-01

    Several air pollution transport models have been developed at the National Environmental Research Institute in Denmark over the last decade (DREAM, DEHM, ACDEP and DEOM). A new 3-D nested Eulerian transport-chemistry model: REGIonal high resolutioN Air pollution model (REGINA) is based on modules and parameterisations from these models as well as new methods. The model covers the majority of the Northern Hemisphere with currently one nest implemented. The horizontal resolution in the mother domain is 150 km × 150 km, and the nesting factor is three. A chemical scheme (originally 51 species) has been extended with a detailed description of the ammonia chemistry and implemented in the model. The mesoscale numerical weather prediction model MM5v2 is used as meteorological driver for the model. The concentrations of air pollutants, such as sulphur and nitrogen in various forms, have been calculated, applying zero nesting and one nest. The model setup is currently being validated by comparing calculated values of concentrations to measurements from approximately 100 stations included in the European Monitoring and Evalutation Programme (EMEP). The present paper describes the physical processes and parameterisations of the model together with the modifications of the chemical scheme. Validation of the model calculations by comparison to EMEP measurements for a summer and a winter month is shown and discussed. Furthermore, results from a sensitivity study of the model performance with respect to resolution in emission and meteorology input data is presented. Finally the future prospects of the model are discussed. The overall validation shows that the model performs well with respect to correlation for both monthly and daily mean values.

  16. Defect modelling in an interactive 3-D CAD environment

    NASA Astrophysics Data System (ADS)

    Reilly, D.; Potts, A.; McNab, A.; Toft, M.; Chapman, R. K.

    2000-05-01

    This paper describes enhancement of the NDT Workbench, as presented at QNDE '98, to include theoretical models for the ultrasonic inspection of smooth planar defects, developed by British Energy and BNFL-Magnox Generation. The Workbench is a PC-based software package for the reconstruction, visualization and analysis of 3-D ultrasonic NDT data in an interactive CAD environment. This extension of the Workbeach now provides the user with a well established modelling approach, coupled with a graphical user interface for: a) configuring the model for flaw size, shape, orientation and location; b) flexible specification of probe parameters; c) selection of scanning surface and scan pattern on the CAD component model; d) presentation of the output as a simulated ultrasound image within the component, or as graphical or tabular displays. The defect modelling facilities of the Workbench can be used for inspection procedure assessment and confirmation of data interpretation, by comparison of overlay images generated from real and simulated data. The modelling technique currently implemented is based on the Geometrical Theory of Diffraction, for simulation of strip-like, circular or elliptical crack responses in the time harmonic or time dependent cases. Eventually, the Workbench will also allow modelling using elastodynamic Kirchhoff theory.

  17. 3D model generation using an airborne swarm

    NASA Astrophysics Data System (ADS)

    Clark, R. A.; Punzo, G.; Dobie, G.; MacLeod, C. N.; Summan, R.; Pierce, G.; Macdonald, M.; Bolton, G.

    2015-03-01

    Using an artificial kinematic field to provide co-ordination between multiple inspection UAVs, the authors herein demonstrate full 3D modelling capability based on a photogrammetric system. The operation of the system is demonstrated by generating a full 3D surface model of an intermediate level nuclear waste storage drum. Such drums require periodic inspection to ensure that drum distortion or corrosion is carefully monitored. Performing this inspection with multiple airborne platforms enables rapid inspection of structures that are inaccessible to on-surface remote vehicles and are in human-hazardous environments. A three-dimensional surface-meshed model of the target can then be constructed in post-processing through photogrammetry analysis of the visual inspection data. The inspection environment uses a tracking system to precisely monitor the position of each aerial vehicle within the enclosure. The vehicles used are commercially available Parrot AR. Drone quadcopters, controlled through a computer interface connected over an IEEE 802.11n (WiFi) network, implementing a distributed controller for each vehicle. This enables the autonomous and distributed elements of the control scheme to be retained, while alleviating the vehicles of the control algorithm's computational load. The control scheme relies on a kinematic field defined with the target at its centre. This field defines the trajectory for all the drones in the volume relative to the central target, enabling the drones to circle the target at a set radius while avoiding drone collisions. This function enables complete coverage along the height of the object, which is assured by transitioning to another inspection band only after completing circumferential coverage. Using a swarm of vehicles, the time until complete coverage can be significantly reduced.

  18. 3-D numerical modeling of plume-induced subduction initiation

    NASA Astrophysics Data System (ADS)

    Baes, Marzieh; Gerya, taras; Sobolev, Stephan

    2016-04-01

    Investigation of mechanisms involved in formation of a new subduction zone can help us to better understand plate tectonics. Despite numerous previous studies, it is still unclear how and where an old oceanic plate starts to subduct beneath the other plate. One of the proposed scenarios for nucleation of subduction is plume-induced subduction initiation, which was investigated in detail, using 2-D models, by Ueda et al. (2008). Recently. Gerya et al. (2015), using 3D numerical models, proposed that plume-lithosphere interaction in the Archean led to the subduction initiation and onset of plate tectonic. In this study, we aim to pursue work of Ueda et al. (2008) by incorporation of 3-D thermo-mechanical models to investigate conditions leading to oceanic subduction initiation as a result of thermal-chemical mantle plume-lithosphere interaction in the modern earth. Results of our experiments show four different deformation regimes in response to plume-lithosphere interaction, that are a) self-sustaining subduction initiation where subduction becomes self-sustained, b) freezing subduction initiation where subduction stops at shallow depths, c) slab break-off where subducting circular slab breaks off soon after formation and d) plume underplating where plume does not pass through the lithosphere but spreads beneath it (failed subduction initiation). These different regimes depend on several parameters such as plume's size, composition and temperature, lithospheric brittle/plastic strength, age of the oceanic lithosphere and presence/absence of lithospheric heterogeneities. Results show that subduction initiates and becomes self-sustained when lithosphere is older than 10 Myr and non-dimensional ratio of the plume buoyancy force and lithospheric strength above the plume is higher than 2.

  19. 3D model generation using an airborne swarm

    SciTech Connect

    Clark, R. A.; Punzo, G.; Macdonald, M.; Dobie, G.; MacLeod, C. N.; Summan, R.; Pierce, G.; Bolton, G.

    2015-03-31

    Using an artificial kinematic field to provide co-ordination between multiple inspection UAVs, the authors herein demonstrate full 3D modelling capability based on a photogrammetric system. The operation of the system is demonstrated by generating a full 3D surface model of an intermediate level nuclear waste storage drum. Such drums require periodic inspection to ensure that drum distortion or corrosion is carefully monitored. Performing this inspection with multiple airborne platforms enables rapid inspection of structures that are inaccessible to on-surface remote vehicles and are in human-hazardous environments. A three-dimensional surface-meshed model of the target can then be constructed in post-processing through photogrammetry analysis of the visual inspection data. The inspection environment uses a tracking system to precisely monitor the position of each aerial vehicle within the enclosure. The vehicles used are commercially available Parrot AR. Drone quadcopters, controlled through a computer interface connected over an IEEE 802.11n (WiFi) network, implementing a distributed controller for each vehicle. This enables the autonomous and distributed elements of the control scheme to be retained, while alleviating the vehicles of the control algorithm’s computational load. The control scheme relies on a kinematic field defined with the target at its centre. This field defines the trajectory for all the drones in the volume relative to the central target, enabling the drones to circle the target at a set radius while avoiding drone collisions. This function enables complete coverage along the height of the object, which is assured by transitioning to another inspection band only after completing circumferential coverage. Using a swarm of vehicles, the time until complete coverage can be significantly reduced.

  20. Handheld camera 3D modeling system using multiple reference panels

    NASA Astrophysics Data System (ADS)

    Fujimura, Kouta; Oue, Yasuhiro; Terauchi, Tomoya; Emi, Tetsuichi

    2002-03-01

    A novel 3D modeling system in which a target object is easily captured and modeled by using a hand-held camera with several reference panels is presented in this paper. The reference panels are designed to be able to obtain the camera position and discriminate between each other. A conventional 3D modeling system using a reference panel has several restrictions regarding the target object, specifically the size and its location. Our system uses multiple reference panels, which are set around the target object to remove these restrictions. The main features of this system are as follows: 1) The whole shape and photo-realistic textures of the target object can be digitized based on several still images or a movie captured by using a hand-held camera; as well as each location of the camera that can be calculated using the reference panels. 2) Our system can be provided as a software product only. That means there are no special requirements for hardware; even the reference panels , because they can be printed from image files or software. 3) This system can be applied to digitize a larger object. In the experiments, we developed and used an interactive region selection tool to detect the silhouette on each image instead of using the chroma -keying method. We have tested our system with a toy object. The calculation time is about 10 minutes (except for the capturing the images and extracting the silhouette by using our tool) on a personal computer with a Pentium-III processor (600MHz) and 320MB memory. However, it depends on how complex the images are and how many images you use. Our future plan is to evaluate the system with various kind of objects, specifically, large ones in outdoor environments.

  1. QSAR models for predicting in vivo aquatic toxicity of chlorinated alkanes to fish.

    PubMed

    Zvinavashe, Elton; van den Berg, Hans; Soffers, Ans E M F; Vervoort, Jacques; Freidig, Andreas; Murk, Albertinka J; Rietjens, Ivonne M C M

    2008-03-01

    Quantitative structure-activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemicals (REACH). The objective of the present study was to generate in vitro acute toxicity data that could be used to develop a QSAR model to describe acute in vivo toxicity of chlorinated alkanes. Cytotoxicity of a series of chlorinated alkanes to Chinese hamster ovary (CHO) cells was observed at concentrations similar to those that have been shown previously to be toxic to fish. Strong correlations exist between the acute in vitro toxicity of the chlorinated alkanes and (i) hydrophobicity [modeled by the calculated log K ow (octanol-water partition coefficient); r (2) = 0.883 and r int (2) = 0.854] and (ii) in vivo acute toxicity to fish ( r (2) = 0.758). A QSAR model has been developed to predict in vivo acute toxicity to fish, based on the in vitro data and even on in silico log K ow data only. The developed QSAR model is applicable to chlorinated alkanes with up to 10 carbon atoms, up to eight chlorine atoms, and log K ow values lying within the range from 1.71 to 5.70. Out of the 100204 compounds on the European Inventory of Existing Chemicals (EINECS), our QSAR model covers 77 (0.1%) of them. Our findings demonstrate that in vitro experiments and even in silico calculations can replace animal experiments in the prediction of the acute toxicity of chlorinated alkanes.

  2. Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models.

    PubMed

    Esposito, Emilio Xavier; Hopfinger, Anton J; Shao, Chi-Yu; Su, Bo-Han; Chen, Sing-Zuo; Tseng, Yufeng Jane

    2015-10-01

    Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted from the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints.

  3. 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.

  4. 3D Model of the Neal Hot Springs Geothermal Area

    DOE Data Explorer

    Faulds, James E.

    2013-12-31

    The Neal Hot Springs geothermal system lies in a left-step in a north-striking, west-dipping normal fault system, consisting of the Neal Fault to the south and the Sugarloaf Butte Fault to the north (Edwards, 2013). The Neal Hot Springs 3D geologic model consists of 104 faults and 13 stratigraphic units. The stratigraphy is sub-horizontal to dipping <10 degrees and there is no predominant dip-direction. Geothermal production is exclusively from the Neal Fault south of, and within the step-over, while geothermal injection is into both the Neal Fault to the south of the step-over and faults within the step-over.

  5. 3D Model of the San Emidio Geothermal Area

    DOE Data Explorer

    James E. Faulds

    2013-12-31

    The San Emidio geothermal system is characterized by a left-step in a west-dipping normal fault system that bounds the western side of the Lake Range. The 3D geologic model consists of 5 geologic units and 55 faults. Overlying Jurrassic-Triassic metasedimentary basement is a ~500 m-1000 m thick section of the Miocene lower Pyramid sequence, pre- syn-extensional Quaternary sedimentary rocks and post-extensional Quaternary rocks. 15-30º eastward dip of the stratigraphy is controlled by the predominant west-dipping fault set. Both geothermal production and injection are concentrated north of the step over in an area of closely spaced west dipping normal faults.

  6. Energy flow in passive and active 3D cochlear model

    NASA Astrophysics Data System (ADS)

    Wang, Yanli; Puria, Sunil; Steele, Charles

    2015-12-01

    Energy flow in the cochlea is an important characteristic of the cochlear traveling wave, and many investigators, such as von Békésy and Lighthill, have discussed this phenomenon. Particularly after the discovery of the motility of the outer hair cells (OHCs), the nature of the power gain of the cochlea has been a fundamental research question. In the present work, direct three-dimensional (3D) calculations of the power on cross sections of the cochlea and on the basilar membrane are performed based on a box model of the mouse cochlea. The distributions of the fluid pressure and fluid velocity in the scala vestibuli are presented. The power output from the OHCs and the power loss due to fluid viscous damping are calculated along the length of the cochlea. This work provides a basis for theoretical calculations of the power gain of the OHCs from mechanical considerations.

  7. Energy flow in passive and active 3D cochlear model

    SciTech Connect

    Wang, Yanli; Steele, Charles; Puria, Sunil

    2015-12-31

    Energy flow in the cochlea is an important characteristic of the cochlear traveling wave, and many investigators, such as von Békésy and Lighthill, have discussed this phenomenon. Particularly after the discovery of the motility of the outer hair cells (OHCs), the nature of the power gain of the cochlea has been a fundamental research question. In the present work, direct three-dimensional (3D) calculations of the power on cross sections of the cochlea and on the basilar membrane are performed based on a box model of the mouse cochlea. The distributions of the fluid pressure and fluid velocity in the scala vestibuli are presented. The power output from the OHCs and the power loss due to fluid viscous damping are calculated along the length of the cochlea. This work provides a basis for theoretical calculations of the power gain of the OHCs from mechanical considerations.

  8. 3D modeling and raytracing in RPV elbows and nozzles

    SciTech Connect

    Koshy, M.; Isenberg, J.

    1995-12-31

    Three dimensional geometric modeling and ray tracing are used to develop ultrasound inspection procedures for nozzles safe ends and elbows in nuclear reactor pressure vessels and other structures containing cracks or voids. B-spline and analytic conic sections are used to generate 3D outer surfaces and interfaces between regions of contrasting impedance. Voids representing flaws are implanted in the inspection volume. Ray tracing in comer trap or normal incidence is performed to evaluate coverage in pulse-echo or pitch-catch mode. In one scenario, the coverage obtained from search units is designed to achieve the required degree of coverage. Physical experiments have been conducted in which artificially-generated flaws in inner blend regions of reactor pressure vessels are inspected using ultrasound from 2.25 mhz transducers. Predicted and measured positions of search units from which the flaws can be detected compare favorably.

  9. 3D Printed Molecules and Extended Solid Models for Teaching Symmetry and Point Groups

    ERIC Educational Resources Information Center

    Scalfani, Vincent F.; Vaid, Thomas P.

    2014-01-01

    Tangible models help students and researchers visualize chemical structures in three dimensions (3D). 3D printing offers a unique and straightforward approach to fabricate plastic 3D models of molecules and extended solids. In this article, we prepared a series of digital 3D design files of molecular structures that will be useful for teaching…

  10. 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

  11. Towards Automatic Semantic Labelling of 3D City Models

    NASA Astrophysics Data System (ADS)

    Rook, M.; Biljecki, F.; Diakité, A. A.

    2016-10-01

    The lack of semantic information in many 3D city models is a considerable limiting factor in their use, as a lot of applications rely on semantics. Such information is not always available, since it is not collected at all times, it might be lost due to data transformation, or its lack may be caused by non-interoperability in data integration from other sources. This research is a first step in creating an automatic workflow that semantically labels plain 3D city model represented by a soup of polygons, with semantic and thematic information, as defined in the CityGML standard. The first step involves the reconstruction of the topology, which is used in a region growing algorithm that clusters upward facing adjacent triangles. Heuristic rules, embedded in a decision tree, are used to compute a likeliness score for these regions that either represent the ground (terrain) or a RoofSurface. Regions with a high likeliness score, to one of the two classes, are used to create a decision space, which is used in a support vector machine (SVM). Next, topological relations are utilised to select seeds that function as a start in a region growing algorithm, to create regions of triangles of other semantic classes. The topological relationships of the regions are used in the aggregation of the thematic building features. Finally, the level of detail is detected to generate the correct output in CityGML. The results show an accuracy between 85 % and 99 % in the automatic semantic labelling on four different test datasets. The paper is concluded by indicating problems and difficulties implying the next steps in the research.

  12. 3D Model of the Tuscarora Geothermal Area

    SciTech Connect

    Faulds, James E.

    2013-12-31

    The Tuscarora geothermal system sits within a ~15 km wide left-step in a major west-dipping range-bounding normal fault system. The step over is defined by the Independence Mountains fault zone and the Bull Runs Mountains fault zone which overlap along strike. Strain is transferred between these major fault segments via and array of northerly striking normal faults with offsets of 10s to 100s of meters and strike lengths of less than 5 km. These faults within the step over are one to two orders of magnitude smaller than the range-bounding fault zones between which they reside. Faults within the broad step define an anticlinal accommodation zone wherein east-dipping faults mainly occupy western half of the accommodation zone and west-dipping faults lie in the eastern half of the accommodation zone. The 3D model of Tuscarora encompasses 70 small-offset normal faults that define the accommodation zone and a portion of the Independence Mountains fault zone, which dips beneath the geothermal field. The geothermal system resides in the axial part of the accommodation, straddling the two fault dip domains. The Tuscarora 3D geologic model consists of 10 stratigraphic units. Unconsolidated Quaternary alluvium has eroded down into bedrock units, the youngest and stratigraphically highest bedrock units are middle Miocene rhyolite and dacite flows regionally correlated with the Jarbidge Rhyolite and modeled with uniform cumulative thickness of ~350 m. Underlying these lava flows are Eocene volcanic rocks of the Big Cottonwood Canyon caldera. These units are modeled as intracaldera deposits, including domes, flows, and thick ash deposits that change in thickness and locally pinch out. The Paleozoic basement of consists metasedimenary and metavolcanic rocks, dominated by argillite, siltstone, limestone, quartzite, and metabasalt of the Schoonover and Snow Canyon Formations. Paleozoic formations are lumped in a single basement unit in the model. Fault blocks in the eastern

  13. A new 3D dynamical biomechanical tongue model

    NASA Astrophysics Data System (ADS)

    Gerard, Jean-Michel; Perrier, Pascal; Payan, Yohan; Wilhelms-Tricarico, Reiner

    2001-05-01

    A new dynamical biomechanical tongue model is being developed to study speech motor control. In spite of its computational complexity, a 3D representation was chosen in order to account for various contacts between tongue and external structures such as teeth, palate, and vocal tract walls. A fair representation of tongue muscle anatomy is provided, by designing the finite element mesh from the visible human data set (female subject). Model geometry was then matched to a human speaker, so that simulations can be quantitatively compared to experimental MRI data. A set of 11 muscles is modeled, whose role in speech gestures is well established. Each muscle is defined by a set of elements whose elastic properties change with muscle activation. Muscles forces are applied to the tongue model via macrofibers defined within the mesh by muscle specific sets of nodes. These forces are currently specified as step functions. Boundary conditions are set using zero-displacement nodes simulating attachments of tongue on bony structures. The nonlinear mechanical properties of tongue soft tissues are modeled using a hyperelastic material. Three-dimensional tongue deformations generated by each muscle, using FEM software ANSYS for computation, will be presented. Implications for speech motor control will be proposed.

  14. Modeling Electric Current Flow in 3D Fractured Media

    NASA Astrophysics Data System (ADS)

    Demirel, S.; Roubinet, D.; Irving, J.

    2014-12-01

    The study of fractured rocks is extremely important in a variety of research fields and applications such as hydrogeology, hydrocarbon extraction and long-term storage of toxic waste. As fractures are highly conductive structures in comparison to the surrounding rock, their presence can be either an advantage or a drawback. For hydrocarbon extraction, fractures allow for quick and easy access to the resource whereas for toxic waste storage their presence increases the risk of leakage and migration of pollutants. In both cases, the identification of fracture network characteristics is an essential step. Recently, we have developed an approach for modeling electric current flow in 2D fractured media. This approach is based on a discrete-dual-porosity model where fractures are represented explicitly, the matrix is coarsely discretized into blocks, and current flow exchange between the fractures and matrix is analytically evaluated at the fracture-scale and integrated at the block-scale [1]. Although this approach has shown much promise and has proven its efficiency for 2D simulations, its extension to 3D remains to be addressed. To this end, we assume that fractures can be represented as two-dimensional finite planes embedded in the surrounding matrix, and we express analytically the distribution of electric potential at the fracture scale. This fracture-scale expression takes into account the electric-current-flow exchange with the surrounding matrix and flow conservation is enforced at the fracture intersections. The fracture-matrix exchange is then integrated at the matrix-block scale where the electric current flow conservation at the block boundaries is formulated with a modified finite volume method. With the objective of providing a low-computational-cost modeling approach adapted to 3D simulations in fractured media, our model is (i) validated and compared to existing modeling approaches and, (ii) used to evaluate the impact of the presence of fractures on

  15. A multipurpose 3-D grid of stellar models

    NASA Astrophysics Data System (ADS)

    Maíz Apellániz, J.

    2013-05-01

    The last two decades have produced a proliferation of stellar atmosphere grids, evolutionary tracks, and isochrones which are available to the astronomical community from different internet services. However, it is not straightforward (at least for an inexperienced user) to manipulate those models to answer questions of the type: What is the spectral energy distribution of a 9000 K giant? What about its J-band magnitude for different metallicities? What can I tell about the mass of a star if I know that its unreddened B-V color is -0.05 and its luminosity in solar units is 10^5? The answers to those questions are indeed in the models but a series of transformations and combinations involving different variables and models are required to obtain them. To make the available knowledge more user friendly, I have combined a number of state-of-the-art sources to create a 3-D (effective temperature, luminosity, and metallicity) grid of stellar models for which I provide calibrated SEDs and magnitudes as well as auxiliary variables such as mass and age. Furthermore, I have generated a grid of extinguished magnitudes using the recent Maíz Apellániz et al. (2012) extinction laws and incorporated them into the Bayesian code CHORIZOS (Maíz Apellániz 2004).

  16. 3-D Eutrophication Modeling for Lake Simcoe, Canada

    NASA Astrophysics Data System (ADS)

    Lu, Q.; Duckett, F.; Nairn, R.; Brunton, A.

    2006-12-01

    The Lake Simcoe Region Conservation Authority (LSRCA) and the Province of Ontario are undertaking a series of studies to facilitate management of the pressures of population growth in the Lake Simcoe watershed. With rapid population growth and urban development comes additional land clearing, storm water runoff and the discharge of treated sewage, all of which are sources of increased phosphorus loading to Lake Simcoe. Depressed oxygen levels were linked to phosphorous enrichment of the lake, with the resultant stimulation of algal growth in the sunlit upper waters of the lake, and its subsequent senescence and settling into the hypolimnion where bacterial decomposition consumes oxygen from the stratified waters. This poster describes a 3-D hydrodynamic, thermal and water quality model of Lake Simcoe developed using the Danish Hydraulics Institute (DHI) MIKE3 model. The hydrodynamic module includes wind-driven circulation, temperature variation, development of the thermocline and thermal stratification, and hydraulic forcing from inflowing tributaries. This is linked to the water quality module which simulates the eutrophication processes in the response of the lake to loadings of phosphorus, such as algal growth, the growth of aquatic plants and subsequent oxygen consumption. The model has been calibrated against Acoustic Doppler Current Profiler velocity data, plus measured temperature and water quality data at MOE stations in the lake and water intakes. The model is an important assessment tool for the management of the lake and its watersheds, allowing assessment of the impacts of the urban growth and land use change on the water quality in Lake Simcoe.

  17. Indoor Modelling Benchmark for 3D Geometry Extraction

    NASA Astrophysics Data System (ADS)

    Thomson, C.; Boehm, J.

    2014-06-01

    A combination of faster, cheaper and more accurate hardware, more sophisticated software, and greater industry acceptance have all laid the foundations for an increased desire for accurate 3D parametric models of buildings. Pointclouds are the data source of choice currently with static terrestrial laser scanning the predominant tool for large, dense volume measurement. The current importance of pointclouds as the primary source of real world representation is endorsed by CAD software vendor acquisitions of pointcloud engines in 2011. Both the capture and modelling of indoor environments require great effort in time by the operator (and therefore cost). Automation is seen as a way to aid this by reducing the workload of the user and some commercial packages have appeared that provide automation to some degree. In the data capture phase, advances in indoor mobile mapping systems are speeding up the process, albeit currently with a reduction in accuracy. As a result this paper presents freely accessible pointcloud datasets of two typical areas of a building each captured with two different capture methods and each with an accurate wholly manually created model. These datasets are provided as a benchmark for the research community to gauge the performance and improvements of various techniques for indoor geometry extraction. With this in mind, non-proprietary, interoperable formats are provided such as E57 for the scans and IFC for the reference model. The datasets can be found at: http://indoor-bench.github.io/indoor-bench.

  18. Planetary subsurface investigation by 3D visualization model .

    NASA Astrophysics Data System (ADS)

    Seu, R.; Catallo, C.; Tragni, M.; Abbattista, C.; Cinquepalmi, L.

    Subsurface data analysis and visualization represents one of the main aspect in Planetary Observation (i.e. search for water or geological characterization). The data are collected by subsurface sounding radars as instruments on-board of deep space missions. These data are generally represented as 2D radargrams in the perspective of space track and z axes (perpendicular to the subsurface) but without direct correlation to other data acquisition or knowledge on the planet . In many case there are plenty of data from other sensors of the same mission, or other ones, with high continuity in time and in space and specially around the scientific sites of interest (i.e. candidate landing areas or particular scientific interesting sites). The 2D perspective is good to analyse single acquisitions and to perform detailed analysis on the returned echo but are quite useless to compare very large dataset as now are available on many planets and moons of solar system. The best way is to approach the analysis on 3D visualization model generated from the entire stack of data. First of all this approach allows to navigate the subsurface in all directions and analyses different sections and slices or moreover navigate the iso-surfaces respect to a value (or interval). The last one allows to isolate one or more iso-surfaces and remove, in the visualization mode, other data not interesting for the analysis; finally it helps to individuate the underground 3D bodies. Other aspect is the needs to link the on-ground data, as imaging, to the underground one by geographical and context field of view.

  19. Accurate, low-cost 3D-models of gullies

    NASA Astrophysics Data System (ADS)

    Onnen, Nils; Gronz, Oliver; Ries, Johannes B.; Brings, Christine

    2015-04-01

    Soil erosion is a widespread problem in arid and semi-arid areas. The most severe form is the gully erosion. They often cut into agricultural farmland and can make a certain area completely unproductive. To understand the development and processes inside and around gullies, we calculated detailed 3D-models of gullies in the Souss Valley in South Morocco. Near Taroudant, we had four study areas with five gullies different in size, volume and activity. By using a Canon HF G30 Camcorder, we made varying series of Full HD videos with 25fps. Afterwards, we used the method Structure from Motion (SfM) to create the models. To generate accurate models maintaining feasible runtimes, it is necessary to select around 1500-1700 images from the video, while the overlap of neighboring images should be at least 80%. In addition, it is very important to avoid selecting photos that are blurry or out of focus. Nearby pixels of a blurry image tend to have similar color values. That is why we used a MATLAB script to compare the derivatives of the images. The higher the sum of the derivative, the sharper an image of similar objects. MATLAB subdivides the video into image intervals. From each interval, the image with the highest sum is selected. E.g.: 20min. video at 25fps equals 30.000 single images. The program now inspects the first 20 images, saves the sharpest and moves on to the next 20 images etc. Using this algorithm, we selected 1500 images for our modeling. With VisualSFM, we calculated features and the matches between all images and produced a point cloud. Then, MeshLab has been used to build a surface out of it using the Poisson surface reconstruction approach. Afterwards we are able to calculate the size and the volume of the gullies. It is also possible to determine soil erosion rates, if we compare the data with old recordings. The final step would be the combination of the terrestrial data with the data from our aerial photography. So far, the method works well and we

  20. 3D Printing of Molecular Potential Energy Surface Models

    ERIC Educational Resources Information Center

    Lolur, Phalgun; Dawes, Richard

    2014-01-01

    Additive manufacturing, commonly known as 3D printing, is gaining popularity in a variety of applications and has recently become routinely available. Today, 3D printing services are not only found in engineering design labs and through online companies, but also in university libraries offering student access. In addition, affordable options for…

  1. 3D numerical modeling of India-Asia-like collision

    NASA Astrophysics Data System (ADS)

    -Erika Püsök, Adina; Kaus, Boris; Popov, Anton

    2013-04-01

    above a strong mantle lithosphere - the jelly sandwich model (Burov and Watts, 2006). 3D models are thus needed to investigate these hypotheses. However, fully 3D models of the dynamics of continent collision zones have only been developed very recently, and presently most research groups have relied on certain explicit assumptions for their codes. Here, we employ the parallel 3D code LaMEM (Lithosphere and Mantle Evolution Model), with a finite difference staggered grid solver, which is capable of simulating lithospheric deformation while simultaneously taking mantle flow and a free surface into account. We here report on first lithospheric and upper-mantle scale simulations in which the Indian lithosphere is indented into Asia. Acknowledgements. Funding was provided by the European Research Council under the European Community's Seventh Framework Program (FP7/2007-2013) / ERC Grant agreement #258830. Numerical computations have been performed on JUQUEEN of the Jülich high-performance computing center. • Beaumont, C., Jamieson, R.A., Nguyen, M.H., Medvedev, S.E., 2004. Crustal channel flows: 1. Numerical models with applications to the tectonics of the Himalayan-Tibetan orogeny. J. Geophys. Res. 109, B06406. • Burov, E. & Watts, W.S., 2006. The long-term strength of continental lithosphere: "jelly sandwich" or "crème brûlée"?. GSA Today, 16, doi: 10.1130/1052-5173(2006)1016<1134:TLTSOC>1132.1130.CO;1132. • England P., Houseman, G., 1986. Finite strain calculations of continental deformation. 2. Comparison with the India-Asia collision zone. J. Geophys. Res.- Solid Earth and Planets 91 (B3), 3664-3676. • Jackson, J., 2002. Strength of the continental lithosphere: time to abandon the jelly sandwich?. GSA Today, September, 4-10. • Lechmann, S.M., May, D.A., Kaus, B.J.P., Schmalholz, S.M., 2011. Comparing thin-sheet models with 3D multilayer models for continental collision. Geophy. Int. J. doi: 10.1111/j.1365-246X.2011.05164.x • Royden, L.H., Burchfiel, B

  2. 3D-Digital soil property mapping by geoadditive models

    NASA Astrophysics Data System (ADS)

    Papritz, Andreas

    2016-04-01

    In many digital soil mapping (DSM) applications, soil properties must be predicted not only for a single but for multiple soil depth intervals. In the GlobalSoilMap project, as an example, predictions are computed for the 0-5 cm, 5-15 cm, 15-30 cm, 30-60 cm, 60-100 cm, 100-200 cm depth intervals (Arrouays et al., 2014). Legacy soil data are often used for DSM. It is common for such datasets that soil properties were measured for soil horizons or for layers at varying soil depth and with non-constant thickness (support). This poses problems for DSM: One strategy is to harmonize the soil data to common depth prior to the analyses (e.g. Bishop et al., 1999) and conduct the statistical analyses for each depth interval independently. The disadvantage of this approach is that the predictions for different depths are computed independently from each other so that the predicted depth profiles may be unrealistic. Furthermore, the error induced by the harmonization to common depth is ignored in this approach (Orton et al. 2016). A better strategy is therefore to process all soil data jointly without prior harmonization by a 3D-analysis that takes soil depth and geographical position explicitly into account. Usually, the non-constant support of the data is then ignored, but Orton et al. (2016) presented recently a geostatistical approach that accounts for non-constant support of soil data and relies on restricted maximum likelihood estimation (REML) of a linear geostatistical model with a separable, heteroscedastic, zonal anisotropic auto-covariance function and area-to-point kriging (Kyriakidis, 2004.) Although this model is theoretically coherent and elegant, estimating its many parameters by REML and selecting covariates for the spatial mean function is a formidable task. A simpler approach might be to use geoadditive models (Kammann and Wand, 2003; Wand, 2003) for 3D-analyses of soil data. geoAM extend the scope of the linear model with spatially correlated errors to

  3. 3D-Digital soil property mapping by geoadditive models

    NASA Astrophysics Data System (ADS)

    Papritz, Andreas

    2016-04-01

    In many digital soil mapping (DSM) applications, soil properties must be predicted not only for a single but for multiple soil depth intervals. In the GlobalSoilMap project, as an example, predictions are computed for the 0-5 cm, 5-15 cm, 15-30 cm, 30-60 cm, 60-100 cm, 100-200 cm depth intervals (Arrouays et al., 2014). Legacy soil data are often used for DSM. It is common for such datasets that soil properties were measured for soil horizons or for layers at varying soil depth and with non-constant thickness (support). This poses problems for DSM: One strategy is to harmonize the soil data to common depth prior to the analyses (e.g. Bishop et al., 1999) and conduct the statistical analyses for each depth interval independently. The disadvantage of this approach is that the predictions for different depths are computed independently from each other so that the predicted depth profiles may be unrealistic. Furthermore, the error induced by the harmonization to common depth is ignored in this approach (Orton et al. 2016). A better strategy is therefore to process all soil data jointly without prior harmonization by a 3D-analysis that takes soil depth and geographical position explicitly into account. Usually, the non-constant support of the data is then ignored, but Orton et al. (2016) presented recently a geostatistical approach that accounts for non-constant support of soil data and relies on restricted maximum likelihood estimation (REML) of a linear geostatistical model with a separable, heteroscedastic, zonal anisotropic auto-covariance function and area-to-point kriging (Kyriakidis, 2004.) Although this model is theoretically coherent and elegant, estimating its many parameters by REML and selecting covariates for the spatial mean function is a formidable task. A simpler approach might be to use geoadditive models (Kammann and Wand, 2003; Wand, 2003) for 3D-analyses of soil data. geoAM extend the scope of the linear model with spatially correlated errors to

  4. Predicted 3D Model of the Rabies Virus Glycoprotein Trimer.

    PubMed

    Fernando, Bastida-González; Yersin, Celaya-Trejo; José, Correa-Basurto; Paola, Zárate-Segura

    2016-01-01

    The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained. PMID:27294109

  5. Predicted 3D Model of the Rabies Virus Glycoprotein Trimer.

    PubMed

    Fernando, Bastida-González; Yersin, Celaya-Trejo; José, Correa-Basurto; Paola, Zárate-Segura

    2016-01-01

    The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained.

  6. Predicted 3D Model of the Rabies Virus Glycoprotein Trimer

    PubMed Central

    Fernando, Bastida-González; Yersin, Celaya-Trejo; José, Correa-Basurto; Paola, Zárate-Segura

    2016-01-01

    The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained. PMID:27294109

  7. 3D finite element modeling of sliding wear

    NASA Astrophysics Data System (ADS)

    Buentello Hernandez, Rodolfo G.

    Wear is defined as "the removal of material volume through some mechanical process between two surfaces". There are many mechanical situations that can induce wear and each can involve many wear mechanisms. This research focuses on the mechanical wear due to dry sliding between two surfaces. Currently there is a need to identify and compare materials that would endure sliding wear under severe conditions such as high velocities. The high costs associated with the field experimentation of systems subject to high-speed sliding, has prevented the collection of the necessary data required to fully characterize this phenomena. Simulating wear through Finite Elements (FE) would enable its prediction under different scenarios and would reduce experimentation costs. In the aerospace, automotive and weapon industries such a model can aid in material selection, design and/or testing of systems subjected to wear in bearings, gears, brakes, gun barrels, slippers, locomotive wheels, or even rocket test tracks. The 3D wear model presented in this dissertation allows one to reasonably predict high-speed sliding mechanical wear between two materials. The model predictions are reasonable, when compared against those measured on a sled slipper traveling over the Holloman High Speed Tests Track. This slipper traveled a distance of 5,816 meters in 8.14 seconds and reached a maximum velocity of 1,530 m/s.

  8. 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.

  9. Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

    EPA Science Inventory

    The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

  10. Pros and Cons of ID vs. 3D Modeling

    NASA Technical Reports Server (NTRS)

    Klimchuk, James A.

    2012-01-01

    Advances in computing capability have led to tremendous improvements in 3D modeling. Entire active regions are being simulated in what might be described as a first principles way, in which plasma heating is treated self consistently rather than through the specification of heating functions. There are limitations to this approach, however, as actual heating mechanisms on the Sun involve spatial scales orders of magnitude smaller than what these simulations can resolve. Other simulations begin to resolve these scales, but they only treat a tiny volume and do not include the all important coupling with larger scales or with other parts of the atmosphere, and so cannot be readily compared with observations. Finally, ID hydrodynamic models capture the field-aligned evolution of the plasma extremely well and are ideally suited for data comparison, but they treat the heating in a totally ad hoc manner. All of these approaches have important contributions to make, but we must be aware of their limitations. I will highlight some of the strengths. and weaknesses of each.

  11. Object-oriented urban 3D spatial data model organization method

    NASA Astrophysics Data System (ADS)

    Li, Jing-wen; Li, Wen-qing; Lv, Nan; Su, Tao

    2015-12-01

    This paper combined the 3d data model with object-oriented organization method, put forward the model of 3d data based on object-oriented method, implemented the city 3d model to quickly build logical semantic expression and model, solved the city 3d spatial information representation problem of the same location with multiple property and the same property with multiple locations, designed the space object structure of point, line, polygon, body for city of 3d spatial database, and provided a new thought and method for the city 3d GIS model and organization management.

  12. Flexible building primitives for 3D building modeling

    NASA Astrophysics Data System (ADS)

    Xiong, B.; Jancosek, M.; Oude Elberink, S.; Vosselman, G.

    2015-03-01

    3D building models, being the main part of a digital city scene, are essential to all applications related to human activities in urban environments. The development of range sensors and Multi-View Stereo (MVS) technology facilitates our ability to automatically reconstruct level of details 2 (LoD2) models of buildings. However, because of the high complexity of building structures, no fully automatic system is currently available for producing building models. In order to simplify the problem, a lot of research focuses only on particular buildings shapes, and relatively simple ones. In this paper, we analyze the property of topology graphs of object surfaces, and find that roof topology graphs have three basic elements: loose nodes, loose edges, and minimum cycles. These elements have interesting physical meanings: a loose node is a building with one roof face; a loose edge is a ridge line between two roof faces whose end points are not defined by a third roof face; and a minimum cycle represents a roof corner of a building. Building primitives, which introduce building shape knowledge, are defined according to these three basic elements. Then all buildings can be represented by combining such building primitives. The building parts are searched according to the predefined building primitives, reconstructed independently, and grouped into a complete building model in a CSG-style. The shape knowledge is inferred via the building primitives and used as constraints to improve the building models, in which all roof parameters are simultaneously adjusted. Experiments show the flexibility of building primitives in both lidar point cloud and stereo point cloud.

  13. Does rational selection of training and test sets improve the outcome of QSAR modeling?

    PubMed

    Martin, Todd M; Harten, Paul; Young, Douglas M; Muratov, Eugene N; Golbraikh, Alexander; Zhu, Hao; Tropsha, Alexander

    2012-10-22

    Prior to using a quantitative structure activity relationship (QSAR) model for external predictions, its predictive power should be established and validated. In the absence of a true external data set, the best way to validate the predictive ability of a model is to perform its statistical external validation. In statistical external validation, the overall data set is divided into training and test sets. Commonly, this splitting is performed using random division. Rational splitting methods can divide data sets into training and test sets in an intelligent fashion. The purpose of this study was to determine whether rational division methods lead to more predictive models compared to random division. A special data splitting procedure was used to facilitate the comparison between random and rational division methods. For each toxicity end point, the overall data set was divided into a modeling set (80% of the overall set) and an external evaluation set (20% of the overall set) using random division. The modeling set was then subdivided into a training set (80% of the modeling set) and a test set (20% of the modeling set) using rational division methods and by using random division. The Kennard-Stone, minimal test set dissimilarity, and sphere exclusion algorithms were used as the rational division methods. The hierarchical clustering, random forest, and k-nearest neighbor (kNN) methods were used to develop QSAR models based on the training sets. For kNN QSAR, multiple training and test sets were generated, and multiple QSAR models were built. The results of this study indicate that models based on rational division methods generate better statistical results for the test sets than models based on random division, but the predictive power of both types of models are comparable.

  14. Methods for Geometric Data Validation of 3d City Models

    NASA Astrophysics Data System (ADS)

    Wagner, D.; Alam, N.; Wewetzer, M.; Pries, M.; Coors, V.

    2015-12-01

    Geometric quality of 3D city models is crucial for data analysis and simulation tasks, which are part of modern applications of the data (e.g. potential heating energy consumption of city quarters, solar potential, etc.). Geometric quality in these contexts is however a different concept as it is for 2D maps. In the latter case, aspects such as positional or temporal accuracy and correctness represent typical quality metrics of the data. They are defined in ISO 19157 and should be mentioned as part of the metadata. 3D data has a far wider range of aspects which influence their quality, plus the idea of quality itself is application dependent. Thus, concepts for definition of quality are needed, including methods to validate these definitions. Quality on this sense means internal validation and detection of inconsistent or wrong geometry according to a predefined set of rules. A useful starting point would be to have correct geometry in accordance with ISO 19107. A valid solid should consist of planar faces which touch their neighbours exclusively in defined corner points and edges. No gaps between them are allowed, and the whole feature must be 2-manifold. In this paper, we present methods to validate common geometric requirements for building geometry. Different checks based on several algorithms have been implemented to validate a set of rules derived from the solid definition mentioned above (e.g. water tightness of the solid or planarity of its polygons), as they were developed for the software tool CityDoctor. The method of each check is specified, with a special focus on the discussion of tolerance values where they are necessary. The checks include polygon level checks to validate the correctness of each polygon, i.e. closeness of the bounding linear ring and planarity. On the solid level, which is only validated if the polygons have passed validation, correct polygon orientation is checked, after self-intersections outside of defined corner points and edges

  15. Numerical model of sonic boom in 3D kinematic turbulence

    NASA Astrophysics Data System (ADS)

    Coulouvrat, François; Luquet, David; Marchiano, Régis

    2015-10-01

    stratified wind superimposed to a 3D random turbulent realization. Propagation is performed either in the case of a shadow zone or of an atmospheric waveguide. To model the turbulent ABL, the mean flow and the fluctuations are handled separately. The wind fluctuations are generated using the Random Fluctuations Generation method assuming a von Kármán spectrum and a homogeneous and isotropic turbulence. The mean stratified wind is modeled based on the Monin-Obhukov Similarity Theory (MOST). To illustrate the method, the typical case of a sunny day with a strong wind has been chosen. Statistics are obtained on several parameters. It shows the importance of turbulence, which leads to an increase of the mean maximum peak pressure in the shadow zone and to its decrease in the waveguide. Moreover, the formation of random caustics that can lead to an increase of the noise perceived locally is outlined.

  16. Approaches for externally validated QSAR modelling of Nitrated Polycyclic Aromatic Hydrocarbon mutagenicity.

    PubMed

    Gramatica, P; Pilutti, P; Papa, E

    2007-01-01

    Nitrated Polycyclic Aromatic Hydrocarbons (nitro-PAHs), ubiquitous environmental pollutants, are recognized mutagens and carcinogens. A set of mutagenicity data (TA100) for 48 nitro-PAHs was modeled by the Quantitative Structure-Activity Relationships (QSAR) regression method, and OECD principles for QSAR model validation were applied. The proposed Multiple Linear Regression (MLR) models are based on two topological molecular descriptors. The models were validated for predictivity by both internal and external validation. For the external validation, three different splitting approaches, D-optimal Experimental Design, Self Organizing Maps (SOM) and Random Selection by activity sampling, were applied to the original data set in order to compare these methodologies and to select the best descriptors able to model each prediction set chemicals independently of the splitting method applied. The applicability domain was verified by the leverage approach.

  17. Development of topography in 3-D continental-collision models

    NASA Astrophysics Data System (ADS)

    Pusok, A. E.; Kaus, Boris J. P.

    2015-05-01

    Understanding the formation and evolution of high mountain belts, such as the Himalayas and the adjacent Tibetan Plateau, has been the focus of many tectonic and numerical models. Here we employ 3-D numerical simulations to investigate the role that subduction, collision, and indentation play on lithosphere dynamics at convergent margins, and to analyze the conditions under which large topographic plateaus can form in an integrated lithospheric and upper mantle-scale model. Distinct dynamics are obtained for the oceanic subduction side (trench retreat, slab rollback) and the continental-collision side (trench advance, slab detachment, topographic uplift, lateral extrusion). We show that slab pull alone is insufficient to generate high topography in the upper plate, and that external forcing and the presence of strong blocks such as the Tarim Basin are necessary to create and shape anomalously high topographic fronts and plateaus. Moreover, scaling is used to predict four different modes of surface expression in continental-collision models: (I) low-amplitude homogeneous shortening, (II) high-amplitude homogeneous shortening, (III) Alpine-type topography with topographic front and low plateau, and (IV) Tibet-Himalaya-type topography with topographic front and high plateau. Results of semianalytical models suggest that the Argand number governs the formation of high topographic fronts, while the amplitude of plateaus is controlled by the initial buoyancy ratio of the upper plate. Applying these results to natural examples, we show that the Alps belong to regime (III), the Himalaya-Tibet to regime (IV), whereas the Andes-Altiplano fall at the boundary between regimes (III) and (IV).

  18. West Flank Coso, CA FORGE 3D temperature model

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

    x,y,z data of the 3D temperature model for the West Flank Coso FORGE site. Model grid spacing is 250m. The temperature model for the Coso geothermal field used over 100 geothermal production sized wells and intermediate-depth temperature holes. At the near surface of this model, two boundary temperatures were assumed: (1) areas with surface manifestations, including fumaroles along the northeast striking normal faults and northwest striking dextral faults with the hydrothermal field, a temperature of ~104˚C was applied to datum at +1066 meters above sea level elevation, and (2) a near-surface temperature at about 10 meters depth, of 20˚C was applied below the diurnal and annual conductive temperature perturbations. These assumptions were based on heat flow studies conducted at the CVF and for the Mojave Desert. On the edges of the hydrothermal system, a 73˚C/km (4˚F/100’) temperature gradient contour was established using conductive gradient data from shallow and intermediate-depth temperature holes. This contour was continued to all elevation datums between the 20˚C surface and -1520 meters below mean sea level. Because the West Flank is outside of the geothermal field footprint, during Phase 1, the three wells inside the FORGE site were incorporated into the preexisting temperature model. To ensure a complete model was built based on all the available data sets, measured bottom-hole temperature gradients in certain wells were downward extrapolated to the next deepest elevation datum (or a maximum of about 25% of the well depth where conductive gradients are evident in the lower portions of the wells). After assuring that the margins of the geothermal field were going to be adequately modelled, the data was contoured using the Kriging method algorithm. Although the extrapolated temperatures and boundary conditions are not rigorous, the calculated temperatures are anticipated to be within ~6˚C (20˚F), or one contour interval, of the

  19. Critically Assessing the Predictive Power of QSAR Models for Human Liver Microsomal Stability.

    PubMed

    Liu, Ruifeng; Schyman, Patric; Wallqvist, Anders

    2015-08-24

    To lower the possibility of late-stage failures in the drug development process, an up-front assessment of absorption, distribution, metabolism, elimination, and toxicity is commonly implemented through a battery of in silico and in vitro assays. As in vitro data is accumulated, in silico quantitative structure-activity relationship (QSAR) models can be trained and used to assess compounds even before they are synthesized. Even though it is generally recognized that QSAR model performance deteriorates over time, rigorous independent studies of model performance deterioration is typically hindered by the lack of publicly available large data sets of structurally diverse compounds. Here, we investigated predictive properties of QSAR models derived from an assembly of publicly available human liver microsomal (HLM) stability data using variable nearest neighbor (v-NN) and random forest (RF) methods. In particular, we evaluated the degree of time-dependent model performance deterioration. Our results show that when evaluated by 10-fold cross-validation with all available HLM data randomly distributed among 10 equal-sized validation groups, we achieved high-quality model performance from both machine-learning methods. However, when we developed HLM models based on when the data appeared and tried to predict data published later, we found that neither method produced predictive models and that their applicability was dramatically reduced. On the other hand, when a small percentage of randomly selected compounds from data published later were included in the training set, performance of both machine-learning methods improved significantly. The implication is that 1) QSAR model quality should be analyzed in a time-dependent manner to assess their true predictive power and 2) it is imperative to retrain models with any up-to-date experimental data to ensure maximum applicability. PMID:26170251

  20. Critically Assessing the Predictive Power of QSAR Models for Human Liver Microsomal Stability.

    PubMed

    Liu, Ruifeng; Schyman, Patric; Wallqvist, Anders

    2015-08-24

    To lower the possibility of late-stage failures in the drug development process, an up-front assessment of absorption, distribution, metabolism, elimination, and toxicity is commonly implemented through a battery of in silico and in vitro assays. As in vitro data is accumulated, in silico quantitative structure-activity relationship (QSAR) models can be trained and used to assess compounds even before they are synthesized. Even though it is generally recognized that QSAR model performance deteriorates over time, rigorous independent studies of model performance deterioration is typically hindered by the lack of publicly available large data sets of structurally diverse compounds. Here, we investigated predictive properties of QSAR models derived from an assembly of publicly available human liver microsomal (HLM) stability data using variable nearest neighbor (v-NN) and random forest (RF) methods. In particular, we evaluated the degree of time-dependent model performance deterioration. Our results show that when evaluated by 10-fold cross-validation with all available HLM data randomly distributed among 10 equal-sized validation groups, we achieved high-quality model performance from both machine-learning methods. However, when we developed HLM models based on when the data appeared and tried to predict data published later, we found that neither method produced predictive models and that their applicability was dramatically reduced. On the other hand, when a small percentage of randomly selected compounds from data published later were included in the training set, performance of both machine-learning methods improved significantly. The implication is that 1) QSAR model quality should be analyzed in a time-dependent manner to assess their true predictive power and 2) it is imperative to retrain models with any up-to-date experimental data to ensure maximum applicability.

  1. 3D Simulation Modeling of the Tooth Wear Process

    PubMed Central

    Dai, Ning; Hu, Jian; Liu, Hao

    2015-01-01

    Severe tooth wear is the most common non-caries dental disease, and it can seriously affect oral health. Studying the tooth wear process is time-consuming and difficult, and technological tools are frequently lacking. This paper presents a novel method of digital simulation modeling that represents a new way to study tooth wear. First, a feature extraction algorithm is used to obtain anatomical feature points of the tooth without attrition. Second, after the alignment of non-attrition areas, the initial homogeneous surface is generated by means of the RBF (Radial Basic Function) implicit surface and then deformed to the final homogeneous by the contraction and bounding algorithm. Finally, the method of bilinear interpolation based on Laplacian coordinates between tooth with attrition and without attrition is used to inversely reconstruct the sequence of changes of the 3D tooth morphology during gradual tooth wear process. This method can also be used to generate a process simulation of nonlinear tooth wear by means of fitting an attrition curve to the statistical data of attrition index in a certain region. The effectiveness and efficiency of the attrition simulation algorithm are verified through experimental simulation. PMID:26241942

  2. 3D Simulation Modeling of the Tooth Wear Process.

    PubMed

    Dai, Ning; Hu, Jian; Liu, Hao

    2015-01-01

    Severe tooth wear is the most common non-caries dental disease, and it can seriously affect oral health. Studying the tooth wear process is time-consuming and difficult, and technological tools are frequently lacking. This paper presents a novel method of digital simulation modeling that represents a new way to study tooth wear. First, a feature extraction algorithm is used to obtain anatomical feature points of the tooth without attrition. Second, after the alignment of non-attrition areas, the initial homogeneous surface is generated by means of the RBF (Radial Basic Function) implicit surface and then deformed to the final homogeneous by the contraction and bounding algorithm. Finally, the method of bilinear interpolation based on Laplacian coordinates between tooth with attrition and without attrition is used to inversely reconstruct the sequence of changes of the 3D tooth morphology during gradual tooth wear process. This method can also be used to generate a process simulation of nonlinear tooth wear by means of fitting an attrition curve to the statistical data of attrition index in a certain region. The effectiveness and efficiency of the attrition simulation algorithm are verified through experimental simulation.

  3. QSAR Modeling of Imbalanced High-Throughput Screening Data in PubChem

    PubMed Central

    2015-01-01

    Many of the structures in PubChem are annotated with activities determined in high-throughput screening (HTS) assays. Because of the nature of these assays, the activity data are typically strongly imbalanced, with a small number of active compounds contrasting with a very large number of inactive compounds. We have used several such imbalanced PubChem HTS assays to test and develop strategies to efficiently build robust QSAR models from imbalanced data sets. Different descriptor types [Quantitative Neighborhoods of Atoms (QNA) and “biological” descriptors] were used to generate a variety of QSAR models in the program GUSAR. The models obtained were compared using external test and validation sets. We also report on our efforts to incorporate the most predictive of our models in the publicly available NCI/CADD Group Web services (http://cactus.nci.nih.gov/chemical/apps/cap). PMID:24524735

  4. 3D modeling of carbonates petro-acoustic heterogeneities

    NASA Astrophysics Data System (ADS)

    Baden, Dawin; Guglielmi, Yves; Saracco, Ginette; Marié, Lionel; Viseur, Sophie

    2015-04-01

    Characterizing carbonate reservoirs heterogeneity is a challenging issue for Oil & Gas Industry, CO2 sequestration and all kinds of fluid manipulations in natural reservoirs, due to the significant impact of heterogeneities on fluid flow and storage within the reservoir. Although large scale (> meter) heterogeneities such as layers petrophysical contrasts are well addressed by computing facies-based models, low scale (< meter) heterogeneities are often poorly constrained because of the complexity in predicting their spatial arrangement. In this study, we conducted petro-acoustic measurements on cores of different size and diameter (Ø = 1", 1.5" and 5") in order to evaluate anisotropy or heterogeneity in carbonates at different laboratory scales. Different types of heterogeneities which generally occur in carbonate reservoir units (e.g. petrographic, diagenetic, and tectonic related) were sampled. Dry / wet samples were investigated with different ultrasonic apparatus and using different sensors allowing acoustic characterization through a bandwidth varying from 50 to 500 kHz. Comprehensive measurements realized on each samples allowed statistical analyses of petro-acoustic properties such as attenuation, shear and longitudinal wave velocity. The cores properties (geological and acoustic facies) were modeled in 3D using photogrammetry and GOCAD geo-modeler. This method successfully allowed detecting and imaging in three dimensions differential diagenesis effects characterized by the occurrence of decimeter-scale diagenetic horizons in samples assumed to be homogeneous and/or different diagenetic sequences between shells filling and the packing matrix. We then discuss how small interfaces such as cracks, stylolithes and laminations which are also imaged may have guided these differential effects, considering that understanding the processes may be taken as an analogue to actual fluid drainage complexity in deep carbonate reservoir.

  5. A 3D numerical model for Kepler's supernova remnant

    NASA Astrophysics Data System (ADS)

    Toledo-Roy, J. C.; Esquivel, A.; Velázquez, P. F.; Reynoso, E. M.

    2014-07-01

    We present new 3D numerical simulations for Kepler's supernova remnant. In this work we revisit the possibility that the asymmetric shape of the remnant in X-rays is the product of a Type Ia supernova explosion which occurs inside the wind bubble previously created by an AGB companion star. Due to the large peculiar velocity of the system, the interaction of the strong AGB wind with the interstellar medium results in a bow shock structure. In this new model we propose that the AGB wind is anisotropic, with properties such as mass-loss rate and density having a latitude dependence, and that the orientation of the polar axis of the AGB star is not aligned with the direction of motion. The ejecta from the Type Ia supernova explosion is modelled using a power-law density profile, and we let the remnant evolve for 400 yr. We computed synthetic X-ray maps from the numerical results. We find that the estimated size and peculiar X-ray morphology of Kepler's supernova remnant are well reproduced by considering an AGB mass-loss rate of 10-5 M⊙ yr-1, a wind terminal velocity of 10 km s-1, an ambient medium density of 10-3 cm-3 and an explosion energy of 7 × 1050 erg. The obtained total X-ray luminosity of the remnant in this model reaches 6 × 1050 erg, which is within a factor of 2 of the observed value, and the time evolution of the luminosity shows a rate of decrease in recent decades of ˜2.4 per cent yr-1 that is consistent with the observations.

  6. QSAR models for the removal of organic micropollutants in four different river water matrices.

    PubMed

    Sudhakaran, Sairam; Calvin, James; Amy, Gary L

    2012-04-01

    Ozonation is an advanced water treatment process used to remove organic micropollutants (OMPs) such as pharmaceuticals and personal care products (PPCPs). In this study, Quantitative Structure Activity Relationship (QSAR) models, for ozonation and advanced oxidation process (AOP), were developed with percent-removal of OMPs by ozonation as the criterion variable. The models focused on PPCPs and pesticides elimination in bench-scale studies done within natural water matrices: Colorado River, Passaic River, Ohio River and Suwannee synthetic water. The OMPs removal for the different water matrices varied depending on the water quality conditions such as pH, DOC, alkalinity. The molecular descriptors used to define the OMPs physico-chemical properties range from one-dimensional (atom counts) to three-dimensional (quantum-chemical). Based on a statistical modeling approach using more than 40 molecular descriptors as predictors, descriptors influencing ozonation/AOP were chosen for inclusion in the QSAR models. The modeling approach was based on multiple linear regression (MLR). Also, a global model based on neural networks was created, compiling OMPs from all the four river water matrices. The chemically relevant molecular descriptors involved in the QSAR models were: energy difference between lowest unoccupied and highest occupied molecular orbital (E(LUMO)-E(HOMO)), electron-affinity (EA), number of halogen atoms (#X), number of ring atoms (#ring atoms), weakly polar component of the solvent accessible surface area (WPSA) and oxygen to carbon ratio (O/C). All the QSAR models resulted in a goodness-of-fit, R(2), greater than 0.8. Internal and external validations were performed on the models. PMID:22245076

  7. Modeling 3-D Slope Stability of Coastal Bluffs Using 3-D Ground-Water Flow, Southwestern Seattle, Washington

    USGS Publications Warehouse

    Brien, Dianne L.; Reid, Mark E.

    2007-01-01

    Landslides are a common problem on coastal bluffs throughout the world. Along the coastal bluffs of the Puget Sound in Seattle, Washington, landslides range from small, shallow failures to large, deep-seated landslides. Landslides of all types can pose hazards to human lives and property, but deep-seated landslides are of significant concern because their large areal extent can cause extensive property damage. Although many geomorphic processes shape the coastal bluffs of Seattle, we focus on large (greater than 3,000 m3), deepseated, rotational landslides that occur on the steep bluffs along Puget Sound. Many of these larger failures occur in advance outwash deposits of the Vashon Drift (Qva); some failures extend into the underlying Lawton Clay Member of the Vashon Drift (Qvlc). The slope stability of coastal bluffs is controlled by the interplay of three-dimensional (3-D) variations in gravitational stress, strength, and pore-water pressure. We assess 3-D slope-stability using SCOOPS (Reid and others, 2000), a computer program that allows us to search a high-resolution digital-elevation model (DEM) to quantify the relative stability of all parts of the landscape by computing the stability and volume of thousands of potential spherical failures. SCOOPS incorporates topography, 3-D strength variations, and 3-D pore pressures. Initially, we use our 3-D analysis methods to examine the effects of topography and geology by using heterogeneous material properties, as defined by stratigraphy, without pore pressures. In this scenario, the least-stable areas are located on the steepest slopes, commonly in Qva or Qvlc. However, these locations do not agree well with observations of deep-seated landslides. Historically, both shallow colluvial landslides and deep-seated landslides have been observed near the contact between Qva and Qvlc, and commonly occur in Qva. The low hydraulic conductivity of Qvlc impedes ground-water flow, resulting in elevated pore pressures at the

  8. Kernel-based partial least squares: application to fingerprint-based QSAR with model visualization.

    PubMed

    An, Yuling; Sherman, Woody; Dixon, Steven L

    2013-09-23

    Numerous regression-based and machine learning techniques are available for the development of linear and nonlinear QSAR models that can accurately predict biological endpoints. Such tools can be quite powerful in the hands of an experienced modeler, but too frequently a disconnect remains between the modeler and project chemist because the resulting QSAR models are effectively black boxes. As a result, learning methods that yield models that can be visualized in the context of chemical structures are in high demand. In this work, we combine direct kernel-based PLS with Canvas 2D fingerprints to arrive at predictive QSAR models that can be projected onto the atoms of a chemical structure, allowing immediate identification of favorable and unfavorable characteristics. The method is validated using binding affinities for ligands from 10 different protein targets covering 7 distinct protein families. Models with significant predictive ability (test set Q(2) > 0.5) are obtained for 6 of 10 data sets, and fingerprints are shown to consistently outperform large collections of classical physicochemical and topological descriptors. In addition, we demonstrate how a simple bootstrapping technique may be employed to obtain uncertainties that provide meaningful estimates of prediction accuracy.

  9. Verification and Validation of the k-kL Turbulence Model in FUN3D and CFL3D Codes

    NASA Technical Reports Server (NTRS)

    Abdol-Hamid, Khaled S.; Carlson, Jan-Renee; Rumsey, Christopher L.

    2015-01-01

    The implementation of the k-kL turbulence model using multiple computational uid dy- namics (CFD) codes is reported herein. The k-kL model is a two-equation turbulence model based on Abdol-Hamid's closure and Menter's modi cation to Rotta's two-equation model. Rotta shows that a reliable transport equation can be formed from the turbulent length scale L, and the turbulent kinetic energy k. Rotta's equation is well suited for term-by-term mod- eling and displays useful features compared to other two-equation models. An important di erence is that this formulation leads to the inclusion of higher-order velocity derivatives in the source terms of the scale equations. This can enhance the ability of the Reynolds- averaged Navier-Stokes (RANS) solvers to simulate unsteady ows. The present report documents the formulation of the model as implemented in the CFD codes Fun3D and CFL3D. Methodology, veri cation and validation examples are shown. Attached and sepa- rated ow cases are documented and compared with experimental data. The results show generally very good comparisons with canonical and experimental data, as well as matching results code-to-code. The results from this formulation are similar or better than results using the SST turbulence model.

  10. Uncertainty in QSAR predictions.

    PubMed

    Sahlin, Ullrika

    2013-03-01

    It is relevant to consider uncertainty in individual predictions when quantitative structure-activity (or property) relationships (QSARs) are used to support decisions of high societal concern. Successful communication of uncertainty in the integration of QSARs in chemical safety assessment under the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) system can be facilitated by a common understanding of how to define, characterise, assess and evaluate uncertainty in QSAR predictions. A QSAR prediction is, compared to experimental estimates, subject to added uncertainty that comes from the use of a model instead of empirically-based estimates. A framework is provided to aid the distinction between different types of uncertainty in a QSAR prediction: quantitative, i.e. for regressions related to the error in a prediction and characterised by a predictive distribution; and qualitative, by expressing our confidence in the model for predicting a particular compound based on a quantitative measure of predictive reliability. It is possible to assess a quantitative (i.e. probabilistic) predictive distribution, given the supervised learning algorithm, the underlying QSAR data, a probability model for uncertainty and a statistical principle for inference. The integration of QSARs into risk assessment may be facilitated by the inclusion of the assessment of predictive error and predictive reliability into the "unambiguous algorithm", as outlined in the second OECD principle.

  11. In Silico Prediction of Chemically Induced Mutagenicity: How to Use QSAR Models and Interpret Their Results.

    PubMed

    Mombelli, Enrico; Raitano, Giuseppa; Benfenati, Emilio

    2016-01-01

    Information on genotoxicity is an essential piece of information gathering for a comprehensive toxicological characterization of chemicals. Several QSAR models that can predict Ames genotoxicity are freely available for download from the Internet and they can provide relevant information for the toxicological profiling of chemicals. Indeed, they can be straightforwardly used for predicting the presence or absence of genotoxic hazards associated with the interactions of chemicals with DNA.Nevertheless, and despite the ease of use of these models, the scientific challenge is to assess the reliability of information that can be obtained from these tools. This chapter provides instructions on how to use freely available QSAR models and on how to interpret their predictions.

  12. In Silico Prediction of Chemically Induced Mutagenicity: How to Use QSAR Models and Interpret Their Results.

    PubMed

    Mombelli, Enrico; Raitano, Giuseppa; Benfenati, Emilio

    2016-01-01

    Information on genotoxicity is an essential piece of information gathering for a comprehensive toxicological characterization of chemicals. Several QSAR models that can predict Ames genotoxicity are freely available for download from the Internet and they can provide relevant information for the toxicological profiling of chemicals. Indeed, they can be straightforwardly used for predicting the presence or absence of genotoxic hazards associated with the interactions of chemicals with DNA.Nevertheless, and despite the ease of use of these models, the scientific challenge is to assess the reliability of information that can be obtained from these tools. This chapter provides instructions on how to use freely available QSAR models and on how to interpret their predictions. PMID:27311463

  13. 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.

  14. 3D Geologic Model of the Southern Great Basin

    NASA Astrophysics Data System (ADS)

    Wagoner, J. L.; Myers, S. C.

    2006-12-01

    We have constructed a regional 3D geologic model of the southern Great Basin, in support of a seismic wave propagation investigation of the 1993 Nonproliferation Experiment (NPE) at the Nevada Test Site (NTS). The model is centered on the NPE and spans longitude -119.5° to -112.6°, latitude 34.5° to 39.8°, and a depth from the surface to 150 km below sea level. Hence, the model includes the southern half of Nevada, as well as parts of eastern California, western Utah, and a portion of northwestern Arizona. The upper crust is constrained by geologic and geophysical studies, and the lower crust and upper mantle are constrained by geophysical studies. The upper crustal geologic units are Quaternary basin fill, Tertiary deposits, pre-Tertiary deposits, intrusive rocks, and calderas. The lower crust and upper mantle are parameterized with 8 layers, including the Moho. Detailed geologic data, including surface maps, borehole data, and geophysical surveys, were used to define the geology at the NTS. Digital geologic outcrop data were available for both Nevada and Arizona, whereas we scanned and hand digitized geologic maps for California and Utah. Published gravity data (2km spacing) were used to determine the thickness of the Cenozoic deposits and constrain the depth of the basins. The free surface is based on a 10m lateral resolution DEM at the NTS and a 90m resolution DEM elsewhere. The gross geophysical structure of the crust and upper mantle is taken from regional surface-wave studies. Variations in crustal thickness are based on receiver function analysis and a compilation of reflection/refraction studies. We used the Earthvision (Dynamic Graphics, Inc.) software to integrate the geologic and geophysical information into a model of x,y,z,p nodes, where p is an integer index representing the geologic unit. For regional seismic simulations we convert this realistic geologic model into elastic parameters. Upper crustal units are treated as seismically homogeneous

  15. Causation or only correlation? Application of causal inference graphs for evaluating causality in nano-QSAR models

    NASA Astrophysics Data System (ADS)

    Sizochenko, Natalia; Gajewicz, Agnieszka; Leszczynski, Jerzy; Puzyn, Tomasz

    2016-03-01

    In this paper, we suggest that causal inference methods could be efficiently used in Quantitative Structure-Activity Relationships (QSAR) modeling as additional validation criteria within quality evaluation of the model. Verification of the relationships between descriptors and toxicity or other activity in the QSAR model has a vital role in understanding the mechanisms of action. The well-known phrase ``correlation does not imply causation'' reflects insight statistically correlated with the endpoint descriptor may not cause the emergence of this endpoint. Hence, paradigmatic shifts must be undertaken when moving from traditional statistical correlation analysis to causal analysis of multivariate data. Methods of causal discovery have been applied for broader physical insight into mechanisms of action and interpretation of the developed nano-QSAR models. Previously developed nano-QSAR models for toxicity of 17 nano-sized metal oxides towards E. coli bacteria have been validated by means of the causality criteria. Using the descriptors confirmed by the causal technique, we have developed new models consistent with the straightforward causal-reasoning account. It was proven that causal inference methods are able to provide a more robust mechanistic interpretation of the developed nano-QSAR models.In this paper, we suggest that causal inference methods could be efficiently used in Quantitative Structure-Activity Relationships (QSAR) modeling as additional validation criteria within quality evaluation of the model. Verification of the relationships between descriptors and toxicity or other activity in the QSAR model has a vital role in understanding the mechanisms of action. The well-known phrase ``correlation does not imply causation'' reflects insight statistically correlated with the endpoint descriptor may not cause the emergence of this endpoint. Hence, paradigmatic shifts must be undertaken when moving from traditional statistical correlation analysis to causal

  16. Validation of Quantitative Structure-Activity Relationship (QSAR) Model for Photosensitizer Activity Prediction

    PubMed Central

    Frimayanti, Neni; Yam, Mun Li; Lee, Hong Boon; Othman, Rozana; Zain, Sharifuddin M.; Rahman, Noorsaadah Abd.

    2011-01-01

    Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR) method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT) activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA) method. Based on the method, r2 value, r2 (CV) value and r2 prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC50 values ranging from 0.39 μM to 7.04 μM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r2 prediction for external test set) of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set. PMID:22272096

  17. Numerical Results of 3-D Modeling of Moon Accumulation

    NASA Astrophysics Data System (ADS)

    Khachay, Yurie; Anfilogov, Vsevolod; Antipin, Alexandr

    2014-05-01

    For the last time for the model of the Moon usually had been used the model of mega impact in which the forming of the Earth and its sputnik had been the consequence of the Earth's collision with the body of Mercurial mass. But all dynamical models of the Earth's accumulation and the estimations after the Pb-Pb system, lead to the conclusion that the duration of the planet accumulation was about 1 milliard years. But isotopic results after the W-Hf system testify about a very early (5-10) million years, dividing of the geochemical reservoirs of the core and mantle. In [1,2] it is shown, that the account of energy dissipating by the decay of short living radioactive elements and first of all Al26,it is sufficient for heating even small bodies with dimensions about (50-100) km up to the iron melting temperature and can be realized a principal new differentiation mechanism. The inner parts of the melted preplanets can join and they are mainly of iron content, but the cold silicate fragments return to the supply zone and additionally change the content of Moon forming to silicates. Only after the increasing of the gravitational radius of the Earth, the growing area of the future Earth's core can save also the silicate envelope fragments [3]. For understanding the further system Earth-Moon evolution it is significant to trace the origin and evolution of heterogeneities, which occur on its accumulation stage.In that paper we are modeling the changing of temperature,pressure,velocity of matter flowing in a block of 3d spherical body with a growing radius. The boundary problem is solved by the finite-difference method for the system of equations, which include equations which describe the process of accumulation, the Safronov equation, the equation of impulse balance, equation Navier-Stocks, equation for above litho static pressure and heat conductivity in velocity-pressure variables using the Businesque approach.The numerical algorithm of the problem solution in velocity

  18. 3D Geological Model of Nihe ore deposit Constrained by Gravity and Magnetic Modeling

    NASA Astrophysics Data System (ADS)

    Qi, Guang; Yan, Jiayong; Lv, Qingtan; Zhao, Jinhua

    2016-04-01

    We present a case study on using integrated geologic model in mineral exploration at depth. Nihe ore deposit in Anhui Province, is deep hidden ore deposit which was discovered in recent years, this finding is the major driving force of deep mineral exploration work in Luzong. Building 3D elaborate geological model has the important significance for prospecting to deep or surround in this area, and can help us better understand the metallogenic law and ore-controlling regularity. A 3D geological model, extending a depth from +200m to -1500m in Nihe ore deposit, has been compiled from surface geological map, cross-section, borehole logs and amounts of geological inference. And then the 3D geological models have been given physical property parameter for calculating the potential field. Modelling the potential response is proposed as means of evaluating the viability of the 3D geological models, and the evidence of making small changes to the uncertain parts of the original 3D geological models. It is expected that the final models not only reproduce supplied prior geological knowledge, but also explain the observed geophysical data. The workflow used to develop the 3D geologic model in this study includes the three major steps, as follows: (1) Determine the basic information of Model: Defining the 3D limits of the model area, the basic geological and structural unit, and the tectonic contact relations and the sedimentary sequences between these units. (2) 3D model construction: Firstly, a series of 2D geological cross sections over the model area are built by using all kinds of prior information, including surface geology, borehole data, seismic sections, and local geologists' knowledge and intuition. Lastly, we put these sections into a 3D environment according to their profile locations to build a 3D model by using geostatistics method. (3) 3D gravity and magnetic modeling: we calculate the potential field responses of the 3D model, and compare the predicted and

  19. Orbiter/External Tank Mate 3-D Solid Modeling

    NASA Technical Reports Server (NTRS)

    Godfrey, G. S.; Brandt, B.; Rorden, D.; Kapr, F.

    2004-01-01

    This research and development project presents an overview of the work completed while attending a summer 2004 American Society of Engineering Education/National Aeronautics and Space Administration (ASEE/NASA) Faculty Fellowship. This fellowship was completed at the Kennedy Space Center, Florida. The scope of the project was to complete parts, assemblies, and drawings that could be used by Ground Support Equipment (GSE) personnel to simulate situations and scenarios commonplace to the space shuttle Orbiter/External Tank (ET) Mate (50004). This mate takes place in the Vehicle Assembly Building (VAB). These simulations could then be used by NASA engineers as decision-making tools. During the summer of 2004, parts were created that defined the Orbiter/ET structural interfaces. Emphasis was placed upon assemblies that included the Orbiter/ET forward attachment (EO-1), aft left thrust strut (EO-2), aft right tripod support structure (EO-3), and crossbeam and aft feedline/umbilical supports. These assemblies are used to attach the Orbiter to the ET. The Orbiter/ET Mate assembly was then used to compare and analyze clearance distances using different Orbiter hang angles. It was found that a 30-minute arc angle change in Orbiter hang angle affected distance at the bipod strut to Orbiter yoke fitting 8.11 inches. A 3-D solid model library was established as a result of this project. This library contains parts, assemblies, and drawings translated into several formats. This library contains a collection of the following files: sti for sterolithography, stp for neutral file work, shrinkwrap for compression. tiff for photoshop work, jpeg for Internet use, and prt and asm for Pro/Engineer use. This library was made available to NASA engineers so that they could access its contents to make angle, load, and clearance analysis studies. These decision-making tools may be used by Pro/Engineer users and non-users.

  20. Automated robust generation of compact 3D statistical shape models

    NASA Astrophysics Data System (ADS)

    Vrtovec, Tomaz; Likar, Bostjan; Tomazevic, Dejan; Pernus, Franjo

    2004-05-01

    Ascertaining the detailed shape and spatial arrangement of anatomical structures is important not only within diagnostic settings but also in the areas of planning, simulation, intraoperative navigation, and tracking of pathology. Robust, accurate and efficient automated segmentation of anatomical structures is difficult because of their complexity and inter-patient variability. Furthermore, the position of the patient during image acquisition, the imaging device and protocol, image resolution, and other factors induce additional variations in shape and appearance. Statistical shape models (SSMs) have proven quite successful in capturing structural variability. A possible approach to obtain a 3D SSM is to extract reference voxels by precisely segmenting the structure in one, reference image. The corresponding voxels in other images are determined by registering the reference image to each other image. The SSM obtained in this way describes statistically plausible shape variations over the given population as well as variations due to imperfect registration. In this paper, we present a completely automated method that significantly reduces shape variations induced by imperfect registration, thus allowing a more accurate description of variations. At each iteration, the derived SSM is used for coarse registration, which is further improved by describing finer variations of the structure. The method was tested on 64 lumbar spinal column CT scans, from which 23, 38, 45, 46 and 42 volumes of interest containing vertebra L1, L2, L3, L4 and L5, respectively, were extracted. Separate SSMs were generated for each vertebra. The results show that the method is capable of reducing the variations induced by registration errors.

  1. Use of laser 3D surface digitizer in data collection and 3D modeling of anatomical structures

    NASA Astrophysics Data System (ADS)

    Tse, Kelly; Van Der Wall, Hans; Vu, Dzung H.

    2006-02-01

    A laser digitizer (Konica-Minolta Vivid 910) is used to obtain 3-dimensional surface scans of anatomical structures with a maximum resolution of 0.1mm. Placing the specimen on a turntable allows multiple scans allaround because the scanner only captures data from the portion facing its lens. A computer model is generated using 3D modeling software such as Geomagic. The 3D model can be manipulated on screen for repeated analysis of anatomical features, a useful capability when the specimens are rare or inaccessible (museum collection, fossils, imprints in rock formation.). As accurate measurements can be performed on the computer model, instead of taking measurements on actual specimens only at the archeological excavation site e.g., a variety of quantitative data can be later obtained on the computer model in the laboratory as new ideas come to mind. Our group had used a mechanical contact digitizer (Microscribe) for this purpose, but with the surface digitizer, we have been obtaining data sets more accurately and more quickly.

  2. The Use of Qsar and Computational Methods in Drug Design

    NASA Astrophysics Data System (ADS)

    Bajot, Fania

    The application of quantitative structure-activity relationships (QSARs) has significantly impacted the paradigm of drug discovery. Following the successful utilization of linear solvation free-energy relationships (LSERs), numerous 2D- and 3D-QSAR methods have been developed, most of them based on descriptors for hydrophobicity, polarizability, ionic interactions, and hydrogen bonding. QSAR models allow for the calculation of physicochemical properties (e.g., lipophilicity), the prediction of biological activity (or toxicity), as well as the evaluation of absorption, distribution, metabolism, and excretion (ADME). In pharmaceutical research, QSAR has a particular interest in the preclinical stages of drug discovery to replace tedious and costly experimentation, to filter large chemical databases, and to select drug candidates. However, to be part of drug discovery and development strategies, QSARs need to meet different criteria (e.g., sufficient predictivity). This chapter describes the foundation of modern QSAR in drug discovery and presents some current challenges and applications for the discovery and optimization of drug candidates

  3. 3D Spherical Convection Modeling of Venusian Resurfacing Mechanisms

    NASA Astrophysics Data System (ADS)

    Prunty, A. C.; King, S. D.

    2014-12-01

    The surface of Venus is thought to have undergone a global resurfacing event approximately 750 Ma. While several variations and modifications within the proposed resurfacing models exist, two end-member mechanisms can be broadly identified: (1) catastrophic overturns of the lithosphere, and (2) global volcanic resurfacing. We perform high-resolution, 3D spherical convection calculations using CitcomS to determine the conditions in Venus' deep interior necessary for each mechanism to occur. To date, we have focused on modeling episodic overturns of the lithosphere in the stagnant lid regime following the method of van Heck and Tackley (2008), and implementing a temperature-dependent rheology and yield stress. We find in general that lithospheric yielding can occur with a Rayleigh number of the order of 105 and a yield stress of the order of 20 ­- 400 MPa, consistent with the results of van Heck and Tackley. Additionally, we find that the behavior of lithospheric overturn depends strongly on the yield stress. To see this, we systematically increase the Rayleigh number and the yield stress via a priori scaling relationships. We find that models with Rayleigh number between 105 and 108 exhibit some variation of stagnant-lid convection; however, we observe that by varying the yield stress we are able to control the degree to which the overturns consist of the subduction of large, coherent segments of lithosphere as opposed to the formation of a large number of smaller, regional delaminations. We analyze these two modes of overturn by looking at the resultant geoid and topography fields to see if they yield distinguishable signatures. Furthermore, we analyze the spherical harmonic power spectrum of the geoid and topography to determine the extent to which their signatures are contributed from lower mantle anomalies and surface features. We also test the effects of mineral phase transformations and depth­-increasing viscosity on lithospheric overturn behavior by varying

  4. QSAR classification models for the prediction of endocrine disrupting activity of brominated flame retardants.

    PubMed

    Kovarich, Simona; Papa, Ester; Gramatica, Paola

    2011-06-15

    The identification of potential endocrine disrupting (ED) chemicals is an important task for the scientific community due to their diffusion in the environment; the production and use of such compounds will be strictly regulated through the authorization process of the REACH regulation. To overcome the problem of insufficient experimental data, the quantitative structure-activity relationship (QSAR) approach is applied to predict the ED activity of new chemicals. In the present study QSAR classification models are developed, according to the OECD principles, to predict the ED potency for a class of emerging ubiquitary pollutants, viz. brominated flame retardants (BFRs). Different endpoints related to ED activity (i.e. aryl hydrocarbon receptor agonism and antagonism, estrogen receptor agonism and antagonism, androgen and progesterone receptor antagonism, T4-TTR competition, E2SULT inhibition) are modeled using the k-NN classification method. The best models are selected by maximizing the sensitivity and external predictive ability. We propose simple QSARs (based on few descriptors) characterized by internal stability, good predictive power and with a verified applicability domain. These models are simple tools that are applicable to screen BFRs in relation to their ED activity, and also to design safer alternatives, in agreement with the requirements of REACH regulation at the authorization step.

  5. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation†

    PubMed Central

    Jensen, G.E.; Niemelä, J.R.; Wedebye, E.B.; Nikolov, N.G.

    2008-01-01

    A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure–activity relationships (QSARs) is a possibility under the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data and epidemiological human studies), dominant lethal effect in rodents (in vivo) and Drosophila melanogaster sex-linked recessive lethal effect. A structure set of 57,014 European Inventory of Existing Chemical Substances (EINECS) chemicals was screened. A total of 5240 EINECS chemicals, corresponding to 9.2%, were predicted as reproductive toxicants by one or more of the models. The chemicals predicted positive for reproductive toxicity will be submitted to the Danish Environmental Protection Agency as scientific input for a future updated advisory classification list with advisory classifications for concern for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption. PMID:19061080

  6. Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions

    PubMed Central

    Sedykh, Alexander; Fourches, Denis; Duan, Jianmin; Hucke, Oliver; Garneau, Michel; Zhu, Hao; Bonneau, Pierre; Tropsha, Alexander

    2013-01-01

    Purpose Membrane transporters mediate many biological effects of chemicals and play a major role in pharmacokinetics and drug resistance. The selection of viable drug candidates among biologically active compounds requires the assessment of their transporter interaction profiles. Methods Using public sources, we have assembled and curated the largest, to our knowledge, human intestinal transporter database (>5,000 interaction entries for >3,700 molecules). This data was used to develop thoroughly validated classification Quantitative Structure-Activity Relationship (QSAR) models of transport and/or inhibition of several major transporters including MDR1, BCRP, MRP1-4, PEPT1, ASBT, OATP2B1, OCT1, and MCT1. Results & Conclusions QSAR models have been developed with advanced machine learning techniques such as Support Vector Machines, Random Forest, and k Nearest Neighbors using Dragon and MOE chemical descriptors. These models afforded high external prediction accuracies of 71–100% estimated by 5-fold external validation, and showed hit retrieval rates with up to 20-fold enrichment in the virtual screening of DrugBank compounds. The compendium of predictive QSAR models developed in this study can be used for virtual profiling of drug candidates and/or environmental agents with the optimal transporter profiles. PMID:23269503

  7. Using 3D Geometric Models to Teach Spatial Geometry Concepts.

    ERIC Educational Resources Information Center

    Bertoline, Gary R.

    1991-01-01

    An explanation of 3-D Computer Aided Design (CAD) usage to teach spatial geometry concepts using nontraditional techniques is presented. The software packages CADKEY and AutoCAD are described as well as their usefulness in solving space geometry problems. (KR)

  8. Examination of 1D Solar Cell Model Limitations Using 3D SPICE Modeling: Preprint

    SciTech Connect

    McMahon, W. E.; Olson, J. M.; Geisz, J. F.; Friedman, D. J.

    2012-06-01

    To examine the limitations of one-dimensional (1D) solar cell modeling, 3D SPICE-based modeling is used to examine in detail the validity of the 1D assumptions as a function of sheet resistance for a model cell. The internal voltages and current densities produced by this modeling give additional insight into the differences between the 1D and 3D models.

  9. QSAR modeling and prediction of the endocrine-disrupting potencies of brominated flame retardants.

    PubMed

    Papa, Ester; Kovarich, Simona; Gramatica, Paola

    2010-05-17

    In the European Union REACH regulation, the chemicals with particularly harmful behaviors, such as endocrine disruptors (EDs), are subject to authorization, and the identification of safer alternatives to these chemicals is required. In this context, the use of quantitative structure-activity relationships (QSAR) becomes particularly useful to fill the data gap due to the very small number of experimental data available to characterize the environmental and toxicological profiles of new and emerging pollutants with ED behavior such as brominated flame retardants (BFRs). In this study, different QSAR models were developed on different responses of endocrine disruption measured for several BFRs. The multiple linear regression approach was applied to a variety of theoretical molecular descriptors, and the best models, which were identified from all of the possible combinations of the structural variables, were internally validated for their performance using the leave-one-out (Q(LOO)(2) = 73-91%) procedure and scrambling of the responses. External validation was provided, when possible, by splitting the data sets in training and test sets (range of Q(EXT)(2) = 76-90%), which confirmed the predictive ability of the proposed equations. These models, which were developed according to the principles defined by the Organization for Economic Co-operation and Development to improve the regulatory acceptance of QSARs, represent a simple tool for the screening and characterization of BFRs.

  10. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    PubMed Central

    Chavan, Swapnil; Nicholls, Ian A.; Karlsson, Björn C. G.; Rosengren, Annika M.; Ballabio, Davide; Consonni, Viviana; Todeschini, Roberto

    2014-01-01

    A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity. PMID:25302621

  11. 3D Atmospheric Radiative Transfer for Cloud System-Resolving Models: Forward Modelling and Observations

    SciTech Connect

    Howard Barker; Jason Cole

    2012-05-17

    Utilization of cloud-resolving models and multi-dimensional radiative transfer models to investigate the importance of 3D radiation effects on the numerical simulation of cloud fields and their properties.

  12. Transforming 2d Cadastral Data Into a Dynamic Smart 3d Model

    NASA Astrophysics Data System (ADS)

    Tsiliakou, E.; Labropoulos, T.; Dimopoulou, E.

    2013-08-01

    3D property registration has become an imperative need in order to optimally reflect all complex cases of the multilayer reality of property rights and restrictions, revealing their vertical component. This paper refers to the potentials and multiple applications of 3D cadastral systems and explores the current state-of-the art, especially the available software with which 3D visualization can be achieved. Within this context, the Hellenic Cadastre's current state is investigated, in particular its data modeling frame. Presenting the methodologies and specifications addressing the registration of 3D properties, the operating cadastral system's shortcomings and merits are pointed out. Nonetheless, current technological advances as well as the availability of sophisticated software packages (proprietary or open source) call for 3D modeling. In order to register and visualize the complex reality in 3D, Esri's CityEngine modeling software has been used, which is specialized in the generation of 3D urban environments, transforming 2D GIS Data into Smart 3D City Models. The application of the 3D model concerns the Campus of the National Technical University of Athens, in which a complex ownership status is established along with approved special zoning regulations. The 3D model was built using different parameters based on input data, derived from cadastral and urban planning datasets, as well as legal documents and architectural plans. The process resulted in a final 3D model, optimally describing the cadastral situation and built environment and proved to be a good practice example of 3D visualization.

  13. Multi Sensor Data Integration for AN Accurate 3d Model Generation

    NASA Astrophysics Data System (ADS)

    Chhatkuli, S.; Satoh, T.; Tachibana, K.

    2015-05-01

    The aim of this paper is to introduce a novel technique of data integration between two different data sets, i.e. laser scanned RGB point cloud and oblique imageries derived 3D model, to create a 3D model with more details and better accuracy. In general, aerial imageries are used to create a 3D city model. Aerial imageries produce an overall decent 3D city models and generally suit to generate 3D model of building roof and some non-complex terrain. However, the automatically generated 3D model, from aerial imageries, generally suffers from the lack of accuracy in deriving the 3D model of road under the bridges, details under tree canopy, isolated trees, etc. Moreover, the automatically generated 3D model from aerial imageries also suffers from undulated road surfaces, non-conforming building shapes, loss of minute details like street furniture, etc. in many cases. On the other hand, laser scanned data and images taken from mobile vehicle platform can produce more detailed 3D road model, street furniture model, 3D model of details under bridge, etc. However, laser scanned data and images from mobile vehicle are not suitable to acquire detailed 3D model of tall buildings, roof tops, and so forth. Our proposed approach to integrate multi sensor data compensated each other's weakness and helped to create a very detailed 3D model with better accuracy. Moreover, the additional details like isolated trees, street furniture, etc. which were missing in the original 3D model derived from aerial imageries could also be integrated in the final model automatically. During the process, the noise in the laser scanned data for example people, vehicles etc. on the road were also automatically removed. Hence, even though the two dataset were acquired in different time period the integrated data set or the final 3D model was generally noise free and without unnecessary details.

  14. Numerical Results of Earth's Core Accumulation 3-D Modelling

    NASA Astrophysics Data System (ADS)

    Khachay, Yurie; Anfilogov, Vsevolod

    2013-04-01

    For a long time as a most convenient had been the model of mega impact in which the early forming of the Earth's core and mantle had been the consequence of formed protoplanet collision with the body of Mercurial mass. But all dynamical models of the Earth's accumulation and the estimations after the Pb-Pb system, lead to the conclusion that the duration of the planet accumulation was about 1 milliard years. But isotopic results after the W-Hf system testify about a very early (5-10) million years, dividing of the geochemical reservoirs of the core and mantle. In [1,3] it is shown, that the account of energy dissipating by the decay of short living radioactive elements and first of all Al,it is sufficient for heating even small bodies with dimensions about (50-100) km up to the iron melting temperature and can be realized a principal new differentiation mechanism. The inner parts of the melted preplanets can join and they are mainly of iron content, but the cold silicate fragments return to the supply zone. Only after the increasing of the gravitational radius, the growing area of the future core can save also the silicate envelope fragments. All existing dynamical accumulation models are constructed by using a spherical-symmetrical model. Hence for understanding the further planet evolution it is significant to trace the origin and evolution of heterogeneities, which occur on the planet accumulation stage. In that paper we are modeling distributions of temperature, pressure, velocity of matter flowing in a block of 3D- spherical body with a growing radius. The boundary problem is solved by the finite-difference method for the system of equations, which include equations which describe the process of accumulation, the Safronov equation, the equation of impulse balance, equation Navier-Stocks, equation for above litho static pressure and heat conductivity in velocity-pressure variables using the Businesque approach. The numerical algorithm of the problem solution in

  15. A novel alternative method for 3D visualisation in Parasitology: the construction of a 3D model of a parasite from 2D illustrations.

    PubMed

    Teo, B G; Sarinder, K K S; Lim, L H S

    2010-08-01

    Three-dimensional (3D) models of the marginal hooks, dorsal and ventral anchors, bars and haptoral reservoirs of a parasite, Sundatrema langkawiense Lim & Gibson, 2009 (Monogenea) were developed using the polygonal modelling method in Autodesk 3ds Max (Version 9) based on two-dimensional (2D) illustrations. Maxscripts were written to rotate the modelled 3D structures. Appropriately orientated 3D haptoral hard-parts were then selected and positioned within the transparent 3D outline of the haptor and grouped together to form a complete 3D haptoral entity. This technique is an inexpensive tool for constructing 3D models from 2D illustrations for 3D visualisation of the spatial relationships between the different structural parts within organisms. PMID:20962723